N = 318) or tacrolimus with MMF . Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P < .05) while CMV, leukopenia, and diarrhea incidences were higher with Tac/MMF (P < .05). The incidence of any antidiabetic treatment for >30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens.In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL,  Tacrolimus combined with various adjunctive agents has been evaluated in clinical trials. Studies have shown that tacrolimus provides good renal allograft function and excellent immunologic protection , 2 and cClinical comparisons of efficacy outcomes between tacrolimus with sirolimus and tacrolimus with MMF have demonstrated similarly low incidences of biopsy-confirmed acute rejection (BCAR). The results of one large multicenter European study revealed comparable BCAR rates between regimens using 0.5 mg sirolimus and 1.0 g MMF but significantly lower incidences of BCAR when a 2 mg dose of sirolimus was administered . ResultsCombining sirolimus with a calcineurin inhibitor (CNI) may accelerate CNI-induced nephrotoxicity especially in the presence of delayed graft function (DGF) . The resIn this multicenter, randomized, clinical trial, we used renal function, as measured by calculated creatinine clearance at 6 months, to compare tacrolimus combined with sirolimus against a tacrolimus and MMF control. Our secondary objective was to compare the efficacy and safety profiles of the two regimens. Unlike other studies, sirolimus was administered in a fixed dose, as opposed to a concentration-controlled dosing concept, and a maintenance dose of 1.0 mg sirolimus was initiated after 28 days.This was a 6-month, randomized, phase III clinical trial conducted in 51 centers in 13 European countries. The study was performed in accordance with the ethical principles described in the amended Declaration of Helsinki following approval from the institutional review committee at each participating center. Patients provided written informed consent prior to study randomization. The study was conducted between October 2004 and July 2006.Patients aged 18 to 60 undergoing primary renal transplantation or retransplantation (unless the graft was lost due to rejection within the previous 12 months) from a deceased or living donor were eligible for study enrollment. Excluded from the study were patients with high immunological risk . Other exclusion criteria included continuously elevated tests of liver function, patient or donor was HIV positive, previous recipient of an organ transplant other than kidney, organ cold ischemia time >30 hours, intolerance to any of the study drugs or the requirement of additional immunosuppressive drugs or antibodies, malignancy, severe hypercholesterolemia (>350 mg/dL or 9.1 mmol/dL), and uncontrolled infection. Patients provided written informed consent before study enrollment. Patient randomization was 1:1, stratified by center and occurred before the first dose of study medication was administered. Sealed randomization envelopes were supplied by the study sponsor. Patients were assigned to treatment with tacrolimus, sirolimus, and steroids (Tac/SRL) or tacrolimus, mycophenolate mofetil, and steroids (Tac/MMF). Tacrolimus was administered in both treatment groups at an initial daily dose of 0.2 mg/kg administered twice (one dose preoperatively and one dose postoperatively). Recommended trough levels for tacrolimus in both groups on days 0 to 14 were 10–15 ng/mL. As the combination of a CNI and sirolimus has been shown to be potentially more nephrotoxic than a CNI and MMF –10, recoA loading dose of sirolimus 6.0 mg was administered with the postoperative dose of tacrolimus and was followed by maintenance doses of 2.0 mg for 28 days and 1.0 mg thereafter. A loading dose of MMF 1.0 g was administered pretransplant followed by a daily dose of 2.0 g for the first 14 days and 1.0 g daily thereafter. Doses of sirolimus and MMF could be reduced or suspended due to medication side effects for no more than 21 days. Adjuvant treatment with corticosteroids was permitted in both regimens using a 100–500 mg bolus dose given peri-operatively and a 125 mg bolus on day 1. Thereafter, steroids were to be steadily tapered from 20 mg on day 2 to 5 mg by day 90 and discontinued on day 91.First line treatment for acute rejection was corticosteroids administered according to local practice; antibody administration was permitted if a biopsy revealed a severe vascular rejection (Banff IIb or III). If rejection was refractory to corticosteroids, then treatment with OKT3 or polyclonal antibodies according to local practice was permitted. Other systemic immunosuppressive medications were prohibited.Pneumocystis carinii pneumonia consisting of cotrimoxazole was required throughout the study. Prophylactic antiviral treatment for CMV in cases where a CMV-positive donor graft was transplanted in a CMV-negative recipient consisting of gancyclovir or equivalent was required.Prophylactic treatment for The primary efficacy endpoint was renal function as measured by calculated creatinine clearance at month 6 (Cockcroft-Gault formula ). Since The outcomes measured in the study were defined as follows. Graft loss: retransplantation, nephrectomy, death or dialysis ongoing at study end or patient withdrawal. DGF: postoperative dialysis for more than one day during the time period from day 0 to day 7. Hypertension: systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg within one measurement. Diabetes mellitus: antidiabetic treatment for >30 consecutive days. Safety assessments included the monitoring of adverse events and vital signs as well as clinical laboratory evaluations. Adverse events were coded using MedDRA (version 8.0). A total of seven scheduled assessment visits took place. Patients were regularly monitored for adverse events.A difference in the mean creatinine clearance of 7.5 mL/min was considered a clinically meaningful margin of noninferiority. Therefore, it was calculated that 225 patients would be required per treatment group to conclude non-inferiority with a power of at least 90%. With an assumed dropout rate of 25%, 600 patients were to be randomized, 300 patients per treatment group. A test for superiority was to be performed without further adjustment of the level of significance if non-inferiority was shown.The full analysis set (FAS), all patients who were randomized, transplanted, and received at least one dose of study medication, was used for analysis. Data from patients belonging to the FAS who completed the study were used to analyze the primary endpoint. Because of the potential bias using observed cases only, a sensitivity analysis of the primary endpoint was performed on all patients with data available at 6 months. Missing values of creatinine clearance were not imputed. P-values of Fisher's exact test.The incidence and time to acute rejection as well as patient and graft survival were analyzed using Kaplan-Meier methods. The difference between treatment groups was analyzed using the Wilcoxon-Gehan test. Two-sided 95% confidence limits for the difference in survival at month 6 were calculated using normal approximation with the variance calculated according to the Greenwood formula. Secondary endpoint variables were analyzed using descriptive statistics. The incidence of adverse events was compared between treatment groups using descriptive In total, 659 patients were enrolled in the study. Of these, 634 underwent transplantation and received at least one dose of study medication , and thus were eligible for the FAS. The treatment groups were comparable with respect to demographic and baseline characteristics. The population was European, predominantly Caucasian with a mean age in the mid-40s, low immunologic risk, with few comorbidities . Approximately 79% of all randomized patients completed the study . The mosProtocol-defined targeted tacrolimus trough levels were different for the two groups after day 14. Despite lower targeted levels after day 14 in the Tac/SRL group, mean trough levels remained above the upper recommended range throughout the study. At month 6, targeted trough level was 4–6 ng/mL, whereas the observed mean level was 7.4 ng/mL . In the The mean (SD) daily administered dose of sirolimus steadily decreased from 1.7 mg (±0.5) at day 28, to 1.0 mg (±0.2) by day 61, and 1.0 mg (±0.2) by month 6 . Similarly, the mean daily dose of MMF decreased from 1.9 g (±0.2) during week 2 to 1.3 g (±0.4) at week 3 and 1.0 g (±0.3) at 6 months . There were no patients in either treatment group who violated protocol and discontinued the adjunct immunosuppressant for >21 days or switched adjunct immunosuppressant. Four patients in the Tac/MMF group completely discontinued taking MMF. Adherence to the protocol-defined withdrawal of steroids at month 3 was low in both groups. At month 4, approximately half of the patients in each group were still taking steroids. By month 5 the numbers of patients maintained on steroids dropped dramatically in both groups. This was 81/318 patients (25.5%) in the TAC/SRL group taking maintenance steroids at a median daily dose of 5.0 mg  and 99/316 patients (31.3%) in the TAC/MMF group taking maintenance steroids at a median daily dose of 5.0 mg . At month 6, maintenance steroids were being taken by 59/318 patients (18.6%) in the Tac/SRL group at a median daily maintenance dose of 5.0 mg  compared with 84/316 patients (26.6%) in the Tac/MMF group taking a median daily maintenance dose of 5.0 mg .The calculated mean creatinine clearance values at 6 months were similar in the two groups. In 250/318 patients (completers) in the Tac/SRL group, the mean creatinine clearance was 66.4 mL/min (SE 1.4), and in 266/316 patients (completers) in the Tac/MMF group, it was 65.2 mL/min (SE 1.3) . The lowDelayed graft function was reported in 64/318 patients (20.1%) in the Tac/SRL group and in 52/316 patients (16.5%) in the Tac/MMF group. Of these patients, dialysis was required by 53 patients (16.7%) in the Tac/SRL group for a median of 10 days (range: 2–76 days) and by slightly fewer patients 45 (14.2%) in the Tac/MMF group for a median of 8 days (range 2–26). There was no difference between the treatment groups in renal function as measured by mean calculated creatinine clearance in patients with and without DGF . Mean seThe overall frequency of acute rejection diagnosed by either clinical signs, symptoms, or biopsy-confirmed was similar in the treatment groups . The proThe overall estimated rate of patients free from BCAR at 6 months (Kaplan-Meier method) was 83.8% in the Tac/SRL group and 87.1% in the Tac/MMF group . More than half of the BCARs in each group occurred during the first two weeks after transplant . In the Patient and graft survival were equivalent between treatment groups . Kaplan-Kaplan-Meier estimates of graft survival rates at month 6 were 92.7% (Tac/SRL [95% CI: 89.8% to 95.6%]) and 93.3% (Tac/MMF [95% CI: 90.5% to 96.1%]). Graft loss due to long-term dialysis or transplantectomy occurring during the study was comparable at 17/318 patients (5.3%) in the Tac/SRL group and 16/316 patients (5.1%) in the Tac/MMF group.P < .05, Fisher's exact test). Conversely, hyperkalemia, CMV infection, nasopharyngitis, leukopenia, and diarrhea occurred significantly more often in patients in the Tac/MMF group . There was no difference in the overall incidence of adverse events which was approximately 93% in each treatment group. A significant difference in the occurrence of several adverse events was found . HyperchTwice as many patients receiving Tac/SRL withdrew due to an adverse event (48/318 [15.1%]) than patients who received Tac/MMF (20/316 [6.3%]). By body system (MedDRA coded), the most commonly reported adverse event leading to study withdrawal in both groups was a renal or urinary disorder . Similar percentages of patients in the Tac/SRL and Tac/MMF groups experienced serious adverse events, 45.9% (146/318) and 43.4% (137/316), and similar percentages of patients experienced adverse events that were assessed by the investigator to be causally related to the study medication, 69.2% (220/318) and 67.7% (214/316), respectively. Two patients in each group were diagnosed with a malignancy during the study. In the Tac/SRL group, 1 patient was diagnosed with lymphoproliferative disease and 1 with an abdominal tumor. In the Tac/MMF group 2 patients were diagnosed with a renal carcinoma. de novo diabetes mellitus was lower in the Tac/SRL than in the Tac/MMF group. Changes in mean serum lipid values were negligible between baseline and month 6 in both treatment groups . There wP = .001, Fisher's exact test).No significant differences between groups were observed in any mean hematology value . As clasThe duration of initial hospitalization as well as the number of episodes of subsequent hospitalizations was similar between the two groups.This large multicenter study investigated the non-inferiority of tacrolimus combined with fixed-dose sirolimus against a standard regimen of tacrolimus combined with MMF by measuring creatinine clearance at 6 months in renal transplant patients. Results showed that a tacrolimus and sirolimus regimen is noninferior to the widely used combination of tacrolimus and MMF. There was no apparent difference in renal function when comparing groups receiving the two different tacrolimus-based combinations. The phase II comparative trial which provided the basis for our trial showed no indication of an influence of sirolimus on renal function when combined with tacrolimus using fixed doses of sirolimus (0.5 mg 1.0 mg or 2 mg) for 6 months , and serFor the primary analysis, we used data from study completers. While an analysis using imputation to account for missing data might yield additional information, it is unlikely that this procedure would provide a different study conclusion. As shown in Using the experience gained from a phase II trial , we implSeveral aspects of regimen tolerability observed in this study are worth mentioning. Firstly, no patient in either treatment group switched the adjuvant immunosuppressant and only four patients in the MMF group discontinued this drug. These results contrast results of a previous study in which a significantly higher rate of drug discontinuation was observed with tacrolimus and sirolimus compared to tacrolimus and MMF (21.1% versus 10.8%) . SecondlThe third aspect of regimen tolerability which should be mentioned is the higher tacrolimus exposure throughout the study in the Tac/SRL group. Although tacrolimus levels in this study were 19% lower than what was reported in the phase II study , the levThe incidences of BCAR we report are in line with prospective study data with incidences ranging from 12% to 24% , 17–19 aThe incidence and type of adverse events reported during the study reflect the known safety profile of both adjunctive therapies (sirolimus and MMF). Study results do not provide clear conclusions in terms of a benefit on safety outcomes of one regimen over the other. Known side effects of MMF therapy, leucopenia, and subsequent infections including CMV infection , 21 wereIn conclusion, results of this study show similarly good renal function at 6 months in renal transplant recipients when tacrolimus is combined with either sirolimus or with MMF. The use of a novel fixed-dose dosing schema for sirolimus was not associated with increased risk of rejection. Both tacrolimus-based regimens provided comparable benefit in this study population.All named authors commented on the study design, took part in the study, and reviewed and approved the final manuscript.The study was funded by Astellas Pharma Europe Ltd, London, UK. The study sponsor was involved in the design of the study, analysis of the data, and preparation of the manuscript. The authors' departments received study grants from Astellas Pharma GmbH (now Astellas Pharma Europe Ltd.) to perform the study. E. Van Gurp, L. Rostaing, T. Becker, E. Rondeau, Z. Czajkowski, A. Alarcon, L. M. Pallardo, B. Rutkowski, and Z. Wlodarczyk. have received fees/sponsorship for speaking/chairing meetings on behalf of Astellas. All other authors declare that they have no conflict of interest.


Various studies have demonstrated that treatment with methyl prednisolone and chlorambucil could increase the chance of remission of idiopathic nephrotic syndrome (INS) of varied histology in patients who do not respond to the conventional treatment. This study was done to assess the safety and efficacy of methyl prednisolone and chlorambucil regimen in patients with various types of glomerulonephritides which were resistant to the usual conventional immunosuppressive drugs. Thirty nine patients were treated between June 1998 and December 2003 with Ponticelli regimen for six months. Twenty three patients (58.98%) were men and 16 (41.02%) were women. Mean age at the onset of NS was 23.59 ± 1.28 (range 10-51) years. Four patients (10.2%) had minimal change disease (MCD), six patients (15.4%) had membranoproliferative glomerulonephritis (MPGN), two (5.1%) had IgA nephropathy, and 18 patients (46.1%) had focal segmental glomerulosclerosis (FSGS). Eleven patients were excluded from the final analysis. Of the remaining 28 patients, mean baseline proteinuria was 3.31 ± 3.09 g/day. Mean baseline plasma albumin was 2.84 ± 1.002 g/dl and mean baseline serum creatinine was 0.87 ± 0.42 mg/dl. At the end of six months of treatment, mean proteinuria was 1.02 ± 0.85 g/day. Mean plasma albumin was 3.69 ± 0.78 g/day, and mean serum creatinine was 0.85 ± 0.26 mg/dl. Mean followup was 13.21 ± 7.7 times in 18.92 ± 12.58 months. At the end of six months of treatment, seven patients (25%) achieved complete remission (CR), 10 patients (35.71%) partial remission (PR), and 11 patients (39.3%) did not show any response to the therapy. Most of the patients in responder group had FSGS (64.70%), whereas in nonresponder group patients had MPGN and mesangioproliferative glomerulonephritis (MesPGN). Out of 13 FSGS cases five (38.46%) achieved CR, six (46.15%) PR, and only two (15.38%) failed to respond. The incidence of side effects was 39.3%. Responders had more side effects than nonresponders (47 vs 27.3%). Methyl prednisolone and chlorambucil therapy (Ponticelli regimen) is safe and efficacious in achieving remission in significant number of INS patients other than membranous nephropathy, without any serious side effect on short term followup. However, a longer followup is required to demonstrate the sustained efficacy and long-term side effect of this regimen. They also observed similar result with the same treatment protocol in steroid resistant NS with FSGS and frequently relapsing (FR) GN with minimal changes disease (MCD) in various studies.[There is no standard therapy for patients with frequent relapsing or steroid-dependent nephrotic syndrome (NS) with primary glomerulonephritides (GN). Similarl studies. Several  studies.We conducted this prospective study to evaluate the safety and efficacy of MP and Chl regimen in patients with various types of GN, who were resistant to the usual immunosuppressive drugs.This was a prospective uncontrolled study. The study group comprised of 39 consecutive patients who were frequent relapsers or steroidresistant NS of varied GN. Informed consent was taken from all patients.Adequate biopsy specimen for light microscopy and immunofluorescence was obtained from all patients and examined by the pathologist of the institute.All patients were followed up monthly for one year and bimonthly for next one year. On each visit the following investigations were carried out: Hemoglobin, total leukocyte count, serum total protein and albumin, creatinine, cholesterol and triglyceride, 24 h urinary protein, and also liver function tests once patients were on levamisole. In addition, patients were clinically evaluated for disease activity and complications. Patients were monitored for following side effects: infections, leukopenia, gastric hemorrhage, diabetes, neoplasia, alopecia, anemia, Cushingoid appearance, gastric discomfort, etc.t’ test were used. P value less than 0.05 was considered as significant.Statistical analysis was done using Microsoft Excel software. Chi square test and Student's ‘P < 0.001) and improvement of plasma albumin from baseline value (P < 0.001) [P < 0.05) by Chi-square test.The present study was commenced in June 1998. It was a prospective uncontrolled study to assess the safety and efficacy of MP and Chl regimen in patients with various types of GN, who were resistant to the usual conventional immunosuppressive drugs. A total of 39 patients were prospectively recruited. Twenty three patients were men (58.98%) and 16 41.02%) were women. Of these 33 (84.61%) were SR, five (12.82%) were FR, and one (2.56%) patient was SD. Mean age at the onset of NS was 23.59 ± 11.28 years (range 10-51 years). Mean duration of disease was 31.84 months (1–120 months). The demographic, clinical, and biochemical details, and histopathology of patients at enrollment are shown in < 0.001) . Serum c1.02% werFSGS responded better than other three groups in our study . Out of As shown in et al., showed that, out of total 15 cases with FSGS, CR was observed in 30% patients, PR in 11.1%, and 58.9% patients did not respond.[et al., used Ponticelli protocol in 19 NS patients with FSGS, of which 10 obtained CR in six months.[In this study, intravenous MP, Chl, and low-dose prednisolone combination (Ponticelli regimen) was found to be an effective for NS patients resistant to usual immunosuppressive therapy with various types of GN other than membranous nephropathy. There were no significant differences in clinical presentation and demographic data between responders and nonresponders at baseline. Histopathological type was found to have an impact on the outcome. SRNS with FSGS had a favorable outcome as 11 (64.7%) patients had achieved remission at the end of six-month therapy. Published literature regarding the use of this treatment in various types of GN, other than membranous nephrotic syndrome (MNS), was very little. Ponticelli et al., treated 23 NS children with FSGS with i.v. MP pulses plus oral prednisone and cytotoxic drug, but not as per Ponticelli protocol. After a mean follow-up of 55 months 18 patients were without NS and only one patient had progressed to renal failure. In spite of very aggressive approach side effects were relatively mild in that particular series.[et al., used intravenous MP and Chl in an aggressive manner in 32 SR FSGS children, of which 21 had CR on five-year follow-up.[et al., found that Chl at a cumulative dose of 8 mg/kg is effective in inducing sustained remission in INS.[Mendoza r series. Similarlollow-up. Niaudet n in INS. Most of Treatment of MPGN remains elusive. Symptomatic therapy and good control of hypertension (HTN) are important. In nephrotic patients a course of steroid may be tried. In the presence of an extracapillary GN or a superimposed interstitial nephritis, an aggressive treatment with i.v. MP pulses, oral steroid, and CYC may obtain a substantial recovery of renal function in several patients. We triedet al., had concluded that elderly SR patients with MCD might benefit from a short course of (8–12 weeks) alkylating agent (CYC 2 mg/kg/day or Chl 0.15 mg/kg/day) associated with oral prednisolone at low doses (20–25 mg/day).[et al., also found benefit from eight weeks therapy with CYC 2 mg/kg/day or Chl 0.15 mg/kg/day in MCD.[Out of total three cases of MCD, two patients achieved remission and one did not respond. No article was found in literature regarding use of this treatment in MCD. However in one study Ponticellli rse of 8–2 weeks aet al., in a meta-analysis, showed that the patient with heavy proteinuria benefited from the administration of steroid and/or cytotoxic drug, as 67% of treated patients had CR or PR versus 34% of untreated patients.[Nephrotic syndrome is uncommon in IgA nephropathy and usually associated with a poor prognosis. Schena patients. A speciapatients. We used et al., reported infections in five patients, leukopenia in four patients, diabetes in two patients, anemia in four, and neoplasia in one patient who had received a cumulative dose of Chl of 0.9 g out of 27 patients. Except this, they concluded that six-month course of therapy was generally well tolerated, and in long term no major toxicity was noted.[et al., in their meta-analysis with CYC and Chl, reported leucopoenia in one-third of patients, severe bacterial infections in 1.5% of the patients under CYC, and in 6.8% under Chl. Seizures were observed in 3.6% of children treated with Chl. Malignancies were observed in 14 children after high doses of either drug.[et al., in spite of very aggressive approach found relatively mild side effects.[et al., who also approached aggressively, found slowed growth in four, small cataracts that did not interfere with vision in five, and infections in two (cellulitis and herpes zoster) patients. There were no cases of abdominal striae, DM, or aseptic necrosis of bone.[In the study group, only 11 patients 39.28%) had infection in the form of RTI in four cases (14.28%) and herpes zoster in two cases 10.71%), and all of them recovered with treatment. However, at the initiation of the therapy, four patients had severe side effects (three had pneumonia and one had persistent leukopenia and anemia) and could not complete the course. Leukopenia developed in three patients, which was responded to GM-CSF (leukomax). Ponticelli 1%, and a9.28% had effects. Tune et  of bone. Side effThus, in our study, the overall response rate using Ponticelli protocol in SRNS with FSGS was comparable to that reported previously. This therapy can be effective partially in SR/FR NS with MCD, MPGN, and MesPGN, and ours is probably the first study with these GN. Long-term controlled studies are needed to confirm this. Though side effects are minimal, caution should be taken for leucopoenia and infections such as pneumonia. Long-term follow up is needed to know about malignancy as a side effect. Hence, we conclude that Ponticelli regimen is effective and safe in achieving remission in patients with various types of GN, who were resistant to the usual conventional immunosuppressive drugs. To confirm this, a controlled, multicenter trial of this protocol may be needed.2/h in children for at least one month duration with plasma creatinine stable at < 1.5 mg/dl.Complete remission (CR): A decrease of urinary protein excretion to at least 200 mg/day or < 4 mg/mPartial remission (PR): A reduction in the rate of urinary protein excretion to between 0.21 and 2 g/day for at least one month duration with plasma creatinine stable at < 1.5 mg/dl.Relapse: Reappearance of proteinuria to >0.2 g/day in a patient who had either CR or PR.Renal failure: Persistent doubling of plasma creatinine over the baseline values.No change: Was considered to have taken place if protein excretion was >2 g/day and the level of plasma creatinine was stable or increased by < 50% over basal value.Time of response: The number of days from the start of treatment to the first day of CR or PR.Duration of disease: Onset of disease to the date of renal biopsy.2 /day of prednisolone or after four months of treatment with prednisolone (1 mg/kg b.w./day) in adults.[Steroid resistant (SR): is present in children when NS persists after 4–6 weeks of therapy with a dose of 60 mg/mn adults.Frequent relapses (FR): Initially steroid responsive but relapse at a rate of 2 per 6 months or 3 per 12 months or 6 per 18 months.Steroid dependent (SD): Initially steroid responsive but relapse during tapering of corticosteroid or within two weeks of discontinuing corticosteroid.Treatment protocol: MP (1 gm or 30 mg/kg b.w. in children) was given i.v. for three consecutive days, followed by prednisolone (0.5 mg/kg/day) orally for 27 days (Cycle A). Cycle A was followed by Chl (0.2 mg/kg/day) orally for one month (Cycle B). Cycles A and B were continued at alternate months for three times each. Total duration of treatment was six months.


The aim of this study is to determine the cardiovascular disease (CVD) risk profile of a large UK HIV cohort and how highly active antiretroviral therapy (HAART) affects this.It is a cross-sectional study within a large inner city hospital and neighbouring district hospital. A total of 1021 HIV positive outpatients representative of the complete cohort and 990 who had no previous CVD were included in CVD risk analysis. We recorded demographics, HAART history and CVD risk factors. CVD and coronary heart disease (CHD) risks were calculated using the Framingham (1991) algorithm adjusted for family history.n = 990) was 74% men, 51% Caucasian and 73.1% were on HAART. Mean age was 41 ± 9 years, systolic blood pressure 120 ± 14 mmHg, total cholesterol 4.70 ± 1.05mmol/l, high-density lipoprotein-C 1.32 ± 0.48 mmol/l and 37% smoked. Median CVD risk was 4 (0–56) % in men and 1.4 (0–37) % in women; CHD risks were 3.5 (0–36) % and 0.6 (0–16) %. CVD risk was > 20% in 6% of men and 1% of women and > 10% in 12% of men and 4% of women. CVD risk was higher in Caucasians than other ethnicities; the risk factor contributing most was raised cholesterol. For patients on their first HAART, increased CHD risk  was strongly related to the duration of therapy.The non-CVD cohort (Modifiable risk factors, especially cholesterol, and also duration of HAART, were key determinants of CVD risk.Regular CHD and/or CVD risk assessment should be performed on patients with HIV, especially during HAART therapy. The effect of different HAART regimens on CHD risk should be considered when selecting therapy. There is a higher incidence of observed cardiovascular disease in HIV patients, and this is increased with HIV therapy. Much of the increase has been ascribed to smoking within patients with high risk lifestyle, and the contribution of therapy and its duration to increasing cholesterol is uncertain.This study demonstrates that cholesterol, rather than smoking, is the most important contributor to increased predicted CV/coronary heart disease risk (CHD) risk in our HIV cohort. It also shows that duration of HAART is key, and hence has important implications for the screening and management of patients with HIV infection.Anti-retroviral therapy (HAART) has reduced traditional HIV-associated disease and death . CardiovAd hoc adjustments can be made to CVD risk factor profiles to add the effects of family history of premature CHD, ethnicity and obesity  is a cross-sectional study looking at estimated 10-year CVD and CHD risk, and the metabolic syndrome in HIV, and this study, CREATE 1, concentrates on the former aspects. Recruitment was from a large inner London teaching hospital with a large HIV cohort (exceeding 2500) and a medium-sized local district hospital with a more affluent demographic.Patients at both hospitals are from a diverse ethnic and socioeconomic group. The study recruited from June 2005 to September 2006.The protocol was approved by the St Thomas’ Hospital Ethics Committee. To minimise selection bias, all HIV-infected outpatients were eligible providing they were regular attendees for their general HIV care and were not pregnant. Patients were not recruited from specialist clinics, such as the lipodystrophy or hepatitis co-infection clinics, to avoid unfair weighting of patients with metabolic issues. These patients were still open to study entry from their general HIV clinic attendance. The research staff identified clinics for inclusion, and all such patients were offered entry.A structured proforma was used to collect data on demographics, basic anthropometry, HIV and HAART history, current CD4 cell counts, HIV viral loads and details of co-infections. Ethnicity was self reported and categorised as: Afro-Caribbean, black African, white (Caucasian), Asian and other. Details of HAART were recorded, including the date of commencement, protease inhibitor use and the current regimen.Anthropometric, physiological and biochemical parameters required to define cardiovascular risk (CVR) and the metabolic syndrome were collected. The use of anti-atheroma therapies, including antithrombotic, antihypertensive, lipid-lowering and hypoglycaemic drugs, was collected, and the use of recreational drugs recorded. Weight, height, waist circumference and blood pressure were measured by trained experienced research nurses or doctors using standard criteria. Blood pressure was measured in the sitting position after 5 min rest with an Omron 320  automated system calibrated to British Hypertension Society standards. Blood lipids were measured fasting when possible, and assayed on a Roche Hitachi  platform by standard techniques of CHOD-PAP for cholesterol and a non-ionic precipitation method for HDL-cholesterol. Data were entered directly onto the proforma during clinic attendance. Missing information on the database was checked with the source data, clinical notes, on scheduled review. The database was regularly cross-checked with the source data.The estimated risk of CVD and CHD was calculated using the Framingham (1991)  equationTo assess CVD risk in a control population, data were compared with the QRESEARCH database , which ispss . This analysis included only patients free of pre-existing CHD diagnoses. Estimated 10-year CHD/CVD risk was summarised using medians and the proportion with values > 10% and > 20% per decade. Subgroups were compared using Chi-squared or Fishers exact test for categorical variables and Mann–Whitney tests for continuous variables. Logistic regression was used to assess the association of HAART use with 10-year CHD risk > 10% and to investigate the extent to which this association was independent of traditional CHD risk factors. The association of duration of HAART use with 10-year CHD risk was examined in a subgroup of patients on first line HAART.Statistical analysis was performed with A total of 1021 patients were recruited, of which 990 were free of pre-existing CVD . For the3, and 73.1% were on HAART. CVD was present in 3% of both men and women, and diabetes in 3% and 2%, respectively. The mean (±SD) age was 41 ± 9 years (48.6%≥ 40 years). Current or recent smoking (within 5 years) was reported by 37% and was commoner in whites  than black Africans. The SBP was 120 ± 14 mmHg, and 11% had a SBP > 140 mmHg. The TC was 4.70 ± 1.05 mmol/l and HDL-C was 1.32 ± 0.48 mmol/l. An elevated TC (> 5 mmol/l) was present in 35.6%. HDL-C < 1 mmol/l in men or < 1.2 mmol/l in women was found in 33%. An elevated TC : HDL ratio > 5 was present in 18.7% and > 6 in 7.6%. Lipid-lowering drugs had been prescribed in 10.8%.The majority, 74%, were men, 50.8% were white, 6.9% Afro-Caribbean, 33.3% African (various), 1.9% Asian and 6.9% from other ethnic groups. Men who have sex with men (MSM) comprised 43.9%, and 41% were heterosexual. Intravenous drug abuse was reported by 1.65%. The median HIV viral load was 50 copies/ml and CD4 count 406 cells/mm2 vs. 23 kg/m2) and a lower prevalence of current smoking (37% vs. 51%).The male population in CREATE 1 was younger (41 years vs. 52 years), contained more smokers (45% vs.13%), had lower SBP (121 mmHg vs. 140 mmHg), slightly lower TC (4.7 mmol/l vs. 5.1 mmol/l) and less established CHD than those self-referring for CVD risk screening in the HEART-UK/Unilever study. Similarly, women recruited to CREATE 1 were younger (39 years vs. 52 years), had lower SBP (118 mmHg vs. 134 mmHg) and cholesterol (4.7 mmol/l vs. 5.2 mmol/l) and less CHD (3% vs. 9%), but more smoked (16% vs.13%). HEART-UK/Unilever participants were markedly different in ethnic origin (92% were non-Caucasian) and were more centrally obese (64% vs. 40%). The population was similar to that recruited to the DAD study cohorts  except fThe median CVD risk was 4 (0–56) %/decade in men and 1.4 (0–37) %/decade in women, whereas CHD risks were 3.5 (0–36) %/decade and 0.6 (0–16) %/decade, respectively. CVD risk was > 20% in 6% of men and 1% of women and > 10% in 12% of men and 4% of women, whereas CHD risk exceeded 10% in 13% of men and 2% of women and was > 20% in 2% of men but no women. CVD risk was lower in all decade cohorts than the HEART-UK/Unilever study, although our patients were significantly younger and had a higher prevalence of smoking . There wAnalyses were performed to investigate the associations of gender, ethnicity (Caucasians vs. non-Caucasians), risk group  and use of HAART with CVD and CHD risk. The median CVD and CHD risks were 4.4% and 2% for men and 1.4% and 1% for women (p < 0.001). The proportions with CVD risk > 10% were 21.8% vs. 3.8% (p < 0.001) and for CHD risk ≥ 10% 16.4% vs. 0.4% (p < 0.001), respectively. Statistically significant differences in CHD risk were also seen for those in older age groups, and groups stratified by TC above or below 5 mmol/l, SBP above or below 140 mmHg and smokers vs. non-smokers (data not shown).Compared with non-Caucasians, Caucasians had greater CVD and CHD risks, and approximately a 3-fold increase in the prevalence of CHD risk > 10% or CVD risk > 20%. These differences could partly be attributed to more men among our Caucasians  hence more MSM individuals , higher viral load , but also higher median CD4 count , more smoking  and lower HDL-C . No significant differences in CVD or CHD risk were observed in MSM compared with male heterosexuals, despite significant differences in age , smoking  and prevalence of drug-treated hypertension  and higher viral loads  and CD4 counts .A total of 705 patients out of 973 were on HAART; 245 were on their first line regimen, of whom 44.1% had used HAART for < 1 year, and about a third and a quarter used HAART for 1–3 years and > 3 years, respectively.Patients on HAART had significantly raised median CVD risk  and CHD  risk, associated with increased age , higher TC , but also lower viral load  and higher HDL-C  .The duration of HAART was associated with CVD and CHD risk. For this analysis, only the 245 participants on first line therapy were included to avoid confounding from previous HAART use. The proportions with 10 year CVD and CHD risk > 20% for those on HAART < 1 year were 4.3% and 0.8% and for ≥ 3 years exposure 11% and 4.8%, respectively (p = 0.01). These differences were statistically significant for both Caucasians and non-Caucasians. A further analysis was performed to define variables within this group associated with increased CVD risk with duration of HAART. Age ≥ 40 years, TC ≥ 5 mmol/l and SBP≥ 140 mmHg were all more common in the group who had been on HAART the longest. Conversely, there were fewer persons with low HDL-C in the ≥ 3 year compared with < 1 year HAART groups, and the TC/HDL ratio did not vary with length of time on HAART . SmokingThe contribution that each Framingham equation variable made to estimated CVD/CHD risk in patients on HAART was investigated. The unadjusted odds ratio for high CVD risk was 1.36  for HAART users vs. non-users. Adjusting for age and gender, the odds ratio fell to 1.13 . Similarly, the unadjusted odds ratio for high CHD risk was 1.59  for HAART users vs. non-users and after adjustment for age and gender, the odds ratio fell to 1.02 . This excess risk was accounted for after adjustment for SBP, smoking and TC; the biggest fall in odds ratio was observed after correction for cholesterol alone (0.63 (0.34–1.20).A similar analysis was performed for 245 patients on first-time HAART according to the duration of HAART  . The unaThe increased frequency of observed CHD in HIV-infected vs. uninfected patients has focused attention on appropriate strategies to prevent cardiovascular disease in this population. Observational cohort studies have shown an increase in observed CVD events with the use of HAART, particularly with protease inhibitors ,21. SomeAmong our UK-based cohort in CREATE1, levels of CVD and CHD risk appeared high compared with similar age groups in the general population, with a higher prevalence of smoking and hypercholesterolaemia. The average CVD and CHD risks in our cohort were 6.0% and 4.15%, respectively. The CHD risk was much lower than the 7–7.4% CHD risk seen in the Italian SIMONE cohort of HIV-infected patients ,23, whern = 245 first line users only). While many guidelines recommend adjustment of the Framingham risk for additional risk factors, this remains controversial. The Framingham risk calculator was derived from data on a mainly white working class population and predicted the correct proportion at risk in patients with HIV in DAD cohort study  and showed pronounced ethnic and gender differences. Smoking was most associated with CVD risk in men and was commoner in Caucasians. In women, the prevalence of smoking was slightly increased compared with the general population. A large proportion of the cohort was heterosexual black African, where smoking was less prevalent than among Caucasians (23% vs. 51%). Therefore, the relative contribution of smoking to CVD risk in this population is likely to be lower than in other studies.The greatest population-attributable risk in the INTERHEART study was dyslipidaemia. Dyslipidaemia is frequent in HIV . DyslipiThese findings provide a rationale for specific policies for the management of CVR in people with HIV, using adaptations of standard guidelines from the Joint British Societies  or NICE


Growth failure, according to the World Health Organization (WHO) definition, was present in one-third of children. A low GFR was associated with growth failure. Poor bladder function evidenced by history of dribbling and significant residual urine was seen in one-third of patients. Residual hydronephrosis was seen in 74%. The most common presenting symptoms of PUV were poor urinary stream followed by recurrent UTI, poor weight gain, renal failure and abdominal mass. Eighty per cent of the study population had undergone surgery in infancy. Five years after surgery, 50% children were symptomatic; 30% had stunting. 33% had a GFR <60 ml/m/1.73 m2 and a significantly greater degree of stunting than those with GFR >60 ml/m/1.73 m2. Sonologically normal kidneys on follow-up were associated with a GFR above 60 ml/m/1.73 m2. Poor bladder function was present in 30% of the children. Univariate analysis showed that statistically significant risk factors for decline in GFR in this study are oligohydramnios and surgery beyond the neonatal period.There are not many studies on long term follow up of children following surgery for posterior urethral valve in India. This study was done to assess the growth and renal function of children who had completed five years after surgery for posterior urethral valve at our hospital. Thirty children were included in this study. They were assessed retrospectively for the age and pattern of presentation, time of surgery and outcome. Outcomes measured were stunting, renal failure  and bladder functions. Fifty per cent of children were symptomatic five years after surgery with enuresis, dribbling, polyuria and recurrent urinary tract infection (UTI). GFR was <60 ml/m/1.73 m Posterior urethral valve (PUV) is the most common congenital anomaly in boys with an incidence of 1 in 8000 male births. It is the most common obstructive cause of end stage renal disease in children.Vesicoureteric reflux, recurrent UTI, voiding dysfunction and late onset renal failure are the long term major problems in these children. There are a few long term outcome studies of children with PUV from India.–3 These The study was conducted at SAT Hospital, Government Medical College, Thiruvananthapuram, between October 2006 and July 2007. Thirty children, with posterior urethral valve five years or more post surgery, were included in the study.The details of children with regard to the age, presenting symptoms, serum creatinine, presence or absence of vesicoureteric reflux at surgery and surgical interventions done were obtained from records. On follow-up, they were assessed clinically. Weight and height were measured using standardized procedures. Biochemical analysis and ultrasound abdomen were done. Outcomes measured were stunting, renal failure  and bladder functions.Stunting was classified according to the WHO norms and grading was done by Waterlows classification of height for age using NCHS standards Table 1Table 1.2) was determined by applying the Schwartz formula:[Glomerular filtration rate (GFR)  followed by recurrent UTI (70%). The other symptoms were poor weight gain, renal failure and abdominal mass. Elevated serum creatinine was present at diagnosis in 63% of patients. 37% of them were oliguric and 57.9% had poor weight gain in infancy.2 at follow-up [The age of the study population at follow-up ranged from 5-16 years with the mean of 7.78 years (2.6). 5 years after surgery, 50% of them were symptomatic. Enuresis was present in 47% patients, dribbling in 43%, polyuria in 40%, muscle cramps in 33%, recurrent UTI in 23% and bone pain in 13%. Of the 30 children included in our study, 33% had a GFR <60ml/m/1.73mollow-up .2, 4 patients ie; 66.7% had stunting.Using the WHO definition of stunting, growth failure was assessed. Stunting is defined by the WHO as a height for age more than a standard deviation of 2 below the median value of the reference population. Nine out of 30 patients i.e. 30% had growth failure. Of the six patients with GFR less than 30 ml/m/1.73 m2 and those with GFR >60 ml/m/1.73 m2. Significant correlation was observed between low GFR and degree of stunting.Using the NCHS reference standards for height and applying Waterlows classification, 43.4% had second degree stunting and 20% had third degree stunting. To study the relation between GFR and growth failure, the study population was divided into two groups – those with GFR <60 ml/m/1.73 mAbout 40% of children had polyuria. Venous bicarbonate levels were done in 26 patients. Of this, 15 patients had a bicarbonate <22 meq/L and 11 patients had a bicarbonate level >22 meq/L.2, GFR 30-60 ml/m/1.73 m2 and GFR >60 ml/m/1.73 m2. In patients with GFR <30 ml/m/1.73 m2, the mean venous bicarbonate was 18.67 meq/L with a SD of 1.5, in those with GFR 30-60 ml/m/1.73 m2, the mean venous bicarbonate was 20.50 with a SD of 1.2 and in patients with GFR >60 ml/m/1.73 m2, the mean venous bicarbonate was 21.6 meq/L with a SD of 2. The results showed statistically significant difference.To study the relation between the presence of acidosis and GFR, the patients were divided into three groups: GFR <30 ml/m/1.73 m2, 9 had acidosis with venous bicarbonate level <22 meq/L i.e.; 90% i.e. There was a statistically significant relation between the severity of acidosis and stage of CKD in this study. 88% (n=22) of the patients with GFR >30 ml/m/1.73 m2 in our study had urine specific gravity ≤1.010.Of the 10 patients with a GFR <60 ml/m/1.73 m2 had bilateral gross hydronephrosis and majority had significant residual urine – these two factors probably contributing to the more rapid deterioration of glomerular function. Those patients with a normal urinary tract on ultrasond abdomen at follow up had a GFR above 60 ml/m/1.73 m2.History of dribbling was present in 43% of children. USS abdomen showed significant residual urine in 30%. There was residual hydronephrosis in 74% patients – bilateral in 55.5% and unilateral in 18.5%. All 6 patients with GFR<30 ml/m/1.73 mUnivariate analysis was done to assess the risk factors for decline in glomerular filtration rate . StatistIn the recent decades, the immediate outcome of boys with PUV has improved continuously with the development of early diagnostic and treatment modalities. However, there is a growing concern over the long term outcome of these children as 24 to 45% of them develop renal failure in childhood or adolescence. Unfavorable prognostic indicators include antenatal presentation before 24 weeks of intrauterine life, renal dysplasia, poor corticomedullary differentiation on ultrasonography, B/L vesicoureteric reflux (VUR) and persistence of high serum creatinine.et al. one-third of patients were detected between 0-1 month, one-third between one month and one year and one-third between one and six years.[Analysis of the clinical presentation of 30 children with PUV showed that the most common symptom at presentation was poor urinary stream followed by recurrent UTI, poor weight gain, renal failure and abdominal mass. Median age at presentation was 3 months. In a study by Parkhouse ix years.Eighty per cent of the study population had undergone surgery in infancy. By univariate analysis, children whose surgery was beyond 28 days had statistically significant risk of poor glomerular function on follow up. Hydronephrosis was detected antenatally in 28.6%. If the amniotic fluid volume is low, the outcome is poor with low GFR. Those with hydronephrosis and oligohydramnios had a poorer outcome than those without oligohydramnios.et al. reported the occurrence of VUR to be 25%.[et al. unilateral VUR was present in 30% and bilateral VUR in 50%.[About 55.2% children had VUR at diagnosis and VUR was bilateral in 41.4%. Study by Parkhouse o be 25%. In a stuR in 50%. In a revet al. 35% had symptomatic voiding dysfunction, the most common symptom being nocturnal enuresis with diurnal urgency and frequency on long term follow-up.[et al. 19% patients had urinary incontinence on follow-up.[Five years after surgery, 50% children were symptomatic. The major symptoms at follow-up were enuresis, dribbling and polyuria. But urodynamic studies could not be done due to lack of facilities for the same. In a study by Lal ollow-up. In the sollow-up. These sy2 in 86.7%, <60 ml/m/1.73 m2 in 33.3% and severe reduction of GFR i.e. <30 ml/m/1.73 m2 in 20% patients. The study by Parkhouse et al. reported poor outcome in one third of patients.[et al. reported that 30% had a GFR <60 ml/m/1.73 m2.[Glomerular filtration rate was decreased i.e. <90 ml/m/1.73 m/1.73 m2.2 had a greater degree of growth failure than those with GFR >60 ml/m/1.73 m2 and the difference was statistically significant. In a study by Tejani et al. with a mean follow-up of nine years, growth failure was present in 40% of patients.[th centile in 52% children.[About 30% of children in our study group had growth failure in the form of stunting according to WHO definition. Those with GFR <60 ml/m/1.73 mpatients. In the let al. also had similar observations. They have reported that children with PUV presenting after two years have higher risk of developing chronic renal insufficiency on long term follow-up.[The severity of metabolic acidosis increased with greater decline in GFR. A statistically significant relation was present between the fall in GFR and acidosis. Poor bladder function was present in 30% of the children as evidenced by significant post void residual urine on ultrasound. This was also associated with low GFR. Statistically significant risk factors in this study for decline in GFR are oligamnios and surgery after the neonatal period. Ansari et al.[et al.[The presence of vescicoureteral reflux was not a risk factor for decline in GFR in our study. This is in contrast to the previous studies by Elisa et al. and Ansal.[et al. The “nadAntenatal detection, counseling of the couple regarding the poor outcome if there is oligohydramnios, early fulguration before 28 days, assessment of GFR before surgery, assessment of yearly GFR, renal growth, tubular functions, bladder functions, optimization of reno protective measures and surgical interventions as and when needed on follow-up are important in the management of all children with posterior urethral valve. Comprehensive care should be the rule by a team comprising pediatrician, pediatric surgeon and pediatric nephrologists for prompt diagnosis and management of upper and lower urinary tract of these children. This will go a long way in reno protection and delaying the occurrence of kidney failure in children with corrected PUV. It also helps in early planning of renal replacement therapies in children with progressive renal insufficiency.


We studied the effect of intraperitoneal COThe RR interval did not change significantly during the study but there was statistically significant increase in QT interval, QTD and QTcD. Minimally invasive surgery has been the most significant development in general surgery as it results in tiny scars and early discharge from the hospital.2 insufflation with head up position in laparoscopic cholecystectomy.12The introduction of laparoscopic cholecystectomy has seen it emerge as the gold standard for the procedure. Equally relevant, it remains the sole procedure performed by the vast majority of general surgeons. Recently much attention has focused on variations of ventricular repolarization because of their relation to cardiac arrhythmia due to prolonged CO2 insufflation on QT interval and QTD during laparoscopic cholecystectomy between the ages of 25 and 65 years.The purpose of this study was to determine the influence of a longer duration of COQT Dispersion is defined as the difference between longest QT interval in any lead and the shortest, for a given set of electrocardiographic leads.3After obtaining the approval from hospital ethics committee, we studied of QT interval and QT dispersion during laparoscopic cholecystectomy randomly in 20 patients of ASA I & II, of either sex, between the ages of 25 and 65 years scheduled for laparoscopic cholecystectomy.2 were monitored. No patients had received any medication. All patients were pre-medicated with IM glycopyrrolate (0.2 mg), IM tramadol (2 mg.kg−1), IV ranitidine (1 mg.kg−1) and IV ondansetron (0.08 mg.kg−1) half an hour before surgery.A detailed history was taken and all patients were examined thoroughly on previous day before surgery and informed consent was obtained. All patients with heart disease and lung disease were excluded from the study. In pre-operative room pulse, BP, SpO2, PETCO2, respiratory rate, temperature (BPL MULTIPARA MONITOR MPM 5553 ACCURA) were monitored before anaesthetic induction (baseline), before CO2 insufflation, every 30 min for 150 min during CO2 insufflation, five minutes after deflation and at the end of surgery.After arriving at the operation room, standard 12 lead digital ECG (BPL CARDIART 8408 VIEW) was attached. Non-invasive blood pressure, SpO−1 and tracheal intubation was facilitated with succinylcholine 2 mg.kg−1. Anaesthesia was maintained with 66% nitrous oxide in O2 supplemented with vecuronium and isoflurane 1-2%. Ventilation was controlled and PET CO2 was maintained between 35 and 40 mm of Hg before CO2 insufflation. All patients received a crystalloid solution and continuous infusion of propofol 4 mg.kg−1.hr−1 during the study.Anaesthesia was induced with propofol 2 mg.kg2 insufflator, achieving and maintaining an intraabdominal pressure 10 to 12 mm of Hg. The minute ventilation was adjusted to maintain PET CO2 between 35 to 40 mm of Hg during the procedure. Patient was moved from supine to head up tilt of 20 degrees during the surgery.42 insufflation was between 120 to 150 minutes.A veress needle was inserted at the umbilical level and connected to the COETCO2, SpO2, temperature were monitored continuously but for the purpose of study they were reached at the same interval. At the end of surgery, neuromuscular blockade was reversed with neostigmine 0.05 mg.kg−1 and glycopyrrolate 0.08 mg.kg−1.From each ECG, consecutive beat-to-beat data were digitally recorded and taken in print out form. QT intervals were determined by the use of newly developed software (BPL CARDIART 8408 VIEW) that detects the onset of Q wave and the end of T wave.6 software. Probability values <0.05 were considered significant.An unpaired students t-test was applied for data analysis. Mean, standard deviation, variance and p value were taken with the help of EPI2 (98.39 ± 0.293) and temperature (98.4 ± 1.01) did not change significantly during the study period. MAP and PETCO2 showed in 2 insufflation.The mean age(years), sex ratio and mean weight(kg) of the patient were 52.35 ± 5.05, 8:12 (M:F) and 64.1 ± 4.17 respectively. Pulse rate, RR interval showed in 2 insufflation (p <0.005) (2 insufflation (p <0.005) (2 insufflation (p < 0.001)  . Similar <0.005) . The QTD< 0.001)  & Fig 4.2 insufflation as similar to study by Joris, et al.7We did not observe changes in PR but MAP was increased during intraperitoneal CO2 insufflation during laparoscopic cholecystectomy induces hemodynamic changes.7Intraperitoneal CO2 insufflation from baseline. The reason is intraperitoneal CO2 insufflation, head up tilt, hypercapnia, inhaled anaesthetics and surgical stress may exert an influence on the QT interval and QTD.58QT interval, QTc interval, QTD and QTcD significantly increased after the start of CO2 insufflation on the QTD during laparoscopy is of considerable interest and the effect of a longer duration of CO2 insufflation on the QTD during laparoscopy remains unclear. Head up tilt induces prolongation of the QTD and QTcD due to increased sympathetic activity or decreased vagal tone.2 insufflation may induce hypercapnia.2The effect of intraperitoneal CO2 should be maintained within normal limits by adjusting minute ventilation during the procedure.PaCOIn our study arrhythmia was not observed may be because we have not included cardiac disease patients.5. Pre operatively QT, QTD was assessed in every patients. QT and QTD increases intraoperatively even in ASA class I & II as observed in our study. So risk factors should be based on that.We did not find any reference suggesting precautions that could be taken at what level but according to many studies99It is concluded that QT dispersion is a simple, non-invasive measurement from a standard 12-lead digital ECG and it makes a significant contribution to identifying the patients at risk for life threatening arrhythmias.As we studied small size population, still more study is required to reach upto definite conclusion.


Accommodative spasm is a rare condition occurring in children, adolescents, and young adults. A familial tendency for this binocular vision disorder has not been reported. I describe accommodative spasm occurring in a brother and sister. Both children presented on the same day with complaints of headaches and blurred vision. Treatment included cycloplegia drops and bifocals. Siblings of patients having accommodative spasm should receive a detailed eye exam with emphasis on recognition of accommodative spasm. Accommodative spasm (AS) is an involuntary condition when there is greater than normal accommodative response than accommodative stimulus. It may b2A 13-year-old Hispanic girl was examined on January 29, 2008 with complaints of severe headaches interfering with her daily activities and blurred vision. Past ocular history was significant for lost glasses for slight myopia which were prescribed by another practitioner. The patient denied any head trauma and was not taking any medication. Presenting visual acuities were 20/400 in each eye. Orthophoria existed at distance, and 2 prism diopters (PD) esophoria at near. Stereopsis was 100 sec of arc. Versions were full as were pupillary responses to light and accommodation. There was no convergence spasm. Dynamic retinoscopy was unstable and could not be quantified. Her refractive error by retinoscopy was -8.00 diopter sphere (DS) – 1.00 Dcylinder (Dcyl) × 162 in the right eye and -4.25 DS – 0.50Dcyl × 108 in the left eye. With 1% cyclogyl, her refraction was -1.00 DS in the right eye and -0.25 DS -0.25 Dcyl × 180 in the left eye which improved visual acuities to 20/80 in each eye. Dilated ophthalmoscopy revealed normal findings. Treatment consisted of prescribing the cycloplegic refraction with a ± 2.50 DS bifocal. On March 4, the patient still had blurred vision at distance with the glasses but reported clear vision at near. Visual acuities were 20/70 in each eye. Repeat cycloplegic refraction was similar to that performed on the first visit. Cyclogyl 1% twice daily was added to the treatment. One month later, the patient reported stinging on instilling the medication and thus used it only one day since the last visit. Visual acuities were 20/80 in each eye. Retinoscopy was -11.75DS -0.25 Dcyl × 117 in the right eye and -11.25DS – 0.25Dcyl × 144 in the left eye. Visual field testing with the tangent screen revealed constricted and tubular fields . TreatmeThe 10-year-old brother was examined on the same day. Similar to his sister, he was suffering from severe headaches and blurred vision. The headaches were worse when reading. This was the child's first eye examination. There was no history of either head trauma or medication. Visual acuities were 20/40 in the right eye and 20/200 in the left eye. Orthophoria existed at distance and near. With the Randot stereo test, 100 sec of arc was measured. Refraction was variable and revealed -2.50DS – 0.50 Dcyl × 90 in the right eye and -3.00 DS in the left eye. With cyclogyl 1%, the refraction was ±0.75 DS in both eyes which improved visual acuity to 20/25 in each eye. All ocular health examination including color vision was normal. Treatment consisted of the cycloplegic refraction findings and a ±2.50 DS addition for near. Compliance with treatment was poor and the glasses were worn infrequently. Visual acuities on March 4, 2008 were 20/50 in right eye and 20/60 in left eye. Cycloplegic refraction was consistent with the prior examination. Added treatment included cyclogy l 1% twice daily in each eye. At the visit on April 1, 2008, the patient had only used the drops once because of its sting. Visual acuities were 20/150 in each eye. Dynamic retinoscopy showed a large lead of accommodation. Refraction was -2.25 DS – 0.50 Dcyl × 82 in right eye and -5.50 DS– 0.50 Dcyl × 13 in left eye. Visual fields with the tangent screen were constricted and tubular . TreatmeTo the best of this author's knowledge, these case reports are the first documentation of AS occurring in siblings. Both children manifested AS without pupillary miosis and convergence spasm, despite the AS measuring more than 11 D for one child (Case 1) on follow-up. The AS in these children may merely be coincidental. On questioning, an older sibling and both parents denied any history of AS. The association in theses siblings suggests a hereditary influence for AS but with no other reported family members and no prior case reports, it remains speculation.in situ keratomileusis (LASIK),[The etiology of AS has been associated with diverse organic causes including closed head trauma,3 multipl (LASIK), acute re (LASIK), and cert (LASIK), AS more  (LASIK), However,Although nonorganic AS can resolve spontaneously over time, treatment is usually indicated because of the severe symptoms. Treatment for AS involves inhibiting the excessive accommodative tone by prescribing bifocals with or without cycloplegic drops. Bifocals alone were insufficient and atropine drops given on weekends were added. Presently, both patients are using atropine drops one day per week with the bifocals. The goal is to wean entirely from the drops and the bifocals and not have the AS recur.In summary, siblings of patients having AS should receive a detailed eye examination with emphasis on recognizing AS.


To the Editor:Ixodes scapularis, the black-legged tick, is the predominant vector of reportable human vectorborne disease in the United States. It transmits agents that cause Lyme borreliosis, human anaplasmosis, and human babesiosis. I. scapularis–borne disease is becoming more frequent as this tick expands its range from tick-endemic foci in the northeastern and upper midwestern United States.I. scapularis established in the state before 2002 were in Menominee County in the Upper Peninsula , active and passive surveillance data indicated that the only populations of I. scapularis populations. Over a 1.5-week period in April–May 2006, we collected adult I. scapularis by drag sampling at 3 recently invaded sites in southwestern Michigan and 2 tick-endemic sites in Menominee County. We targeted adult I. scapularis in the spring because this life stage has had 2 chances of becoming infected and because the adult questing peak in Michigan is greater in spring than fall . We used 3 PCRs to assay for I. scapularis and 2 adult Dermacentor variabilis from tick-endemic sites. Of the adult I. scapularis, 17 (60.7%) were positive for B. burgdorferi, 4 (14.3%) were positive for A. phagocytophilum, and 2 (7.1%) were positive for Babesia odocoilei  were positive for B. burgdorferi, 1 (1.1%) was positive for A. phagocytophilum, and 4 (4.4%) were positive for Babesia odocoilei. All 4 Babesia odocoilei–positive ticks were co-infected with B. burgdorferi .Tick densities were highest overall at tick-endemic Menominee County sites; in southwestern Michigan, they were highest at those sites closest to the putative source of the Indiana invasion. We collected 28 adult and 1 nymphal docoilei . We alsoB. burgdorferi infection rate in adult ticks increased from 31.3% in 1992 to 60.7% in the present survey . A similar increasing trend was evident in the invasion area, where prevalence increased from 37.0% in 2002–2003  to 47.3% in 2006. This latter trend was only marginally statistically significant due to small sample size and the short period between surveys .Within the tick-endemic area, comparison with prior survey data  from US ticks were not detected in our sample. I. scapularis nymphs, which are epidemiologically important . Incidence in the invasion zone has been much lower  but appears to be increasing. Further increases in tick population size, infection, and co-infection can be expected as the invasion continues (These data imply a risk for Lyme borreliosis and human anaplasmosis in areas endemic for and recently invaded by


P < 0.01).The mean level of sTfR in CKD patients was 3.23 ± 2.07 mg/l while in controls this was 5.16 ± 3.64 mg/l. sTfR had no statistically significant correlation with the levels of hemoglobin, iron, ferritin, TIBC and TSAT. We conclude that owing to complexity of iron metabolism in CKD, sTfR can not be used as a reliable marker of iron deficiency anemia.Anemia in patients with chronic renal failure is multifactorial with an absolute or functional iron deficiency present in 60–80% of patients. In this study, 102 patients of stage 5 chronic kidney disease (CKD) were enrolled. Thirty six age- and sex-matched anemic patients without any known renal disease were taken as controls. Their sTfR levels were measured with anemia profile.. The patients were followed up twice, at four weeks and six months. There was a significant statistical difference in the mean sTfR levels in patients when compared to controls ( Chronic kidney disease (CKD) is an important, chronic, noncommunicable epidemic disease that affects the world, including India. Anemia aIn recent years, soluble transferrin receptor (sTfR) has been introduced as a sensitive, early and highly quantitative new marker of iron depletion, increasing in proportion to tissue iron deficit. The tranSynthesis of transferrin receptor and the iron storage protein ferritin are reciprocally linked to cellular iron content. UntranslThe sTfR number on the cell surface reflects the iron requirement of the body. Iron deprivation has been shown to result in prompt induction of sTfR synthesis, whereas no effect is seen in anemia of chronic disease. Erythropoietic activity of bone marrow also affects the levels of sTfR; being decreased by diminished erythropoietic activity and increased when erythropoiesis is increased.The present study was done to ascertain the role of sTfR as a marker of iron deficiency anemia in the patients of CKD undergoing hemodialysis.The study group consisted of 102 adult patients diagnosed to have chronic kidney disease with a GFR < 10 ml / min/1.73 sqm BSA. All patients were on maintenance hemodialysis. Patients with megaloblastic anemia were excluded.Out of 102 patients enrolled in the study, five patients died before the time of first follow up. Out of the rest 97, 55 came for follow up at 4 weeks. One of the patients underwent renal transplantation and four patients died before the time of second follow up at six months. Out of the 50 remaining patients, 25 patients continued the treatment and came for second follow up.These patients were on maintenance hemodialysis biweekly. They were being given weekly injections of recombinant human erythropoietin, subcutaneously as per their requirement. Intravenous iron supplementation was given using Iron (III) hydroxide polymaltose complex or iron sucrose as indicated.The control group (C) consisted of 36 subjects. These patients were being investigated for iron deficiency anemia and had no known renal disease. sTfR levels were measured in 20 samples of apparently healthy individuals also during the study.Anemia was treated in all subjects as per National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF/DOQI) which recommends starting workup for anemia when the hemoglobin is less than 11 g/dl in pre-menopausal females and pre-pubertal patients, and hemoglobin is less than 12 g/dl in adult males and post-menopausal females.Iron was estimated by ‘Ferene-S’ Method and TIBC was quantitatively estimated by Magnesium Carbonate Method on a semi-automated auto analyzer – Clima Plus using Clonital kits. Ferritin was estimated by Electrochemiluminiscene (ECLIA) immunoassay kit from Roche on the Elecsys 1010.sTfR was quantitatively estimated by particle enhanced Immunoturbidimetric Assay kit (Orion Diagnostica) on semiautomated analyzer (Erba Chem. 5 Plus).r’.Results obtained were analyzed using chi-square test, student's‘t’ test and Pearson's coefficient of correlation ‘P < 0.01) [The study included 102 patients and control group of 36 patients. The mean age was 48.56 ± 16.34 years in the study group and 45.91 ± 17.45 years in the control group. Diabetes mellitus was the commonest cause of CKD, with 50 patients (49.02%) suffering from it . The mea < 0.01) .In the 55 patients who were followed up for a minimum of one month there was no statistically significant change in sTfR levels. The 25 patients, who were followed up for 6 months, also did not show any statistically significant change in sTfR levels.μg/dl at baseline and in controls was 66.65± 28.52 μg/dl. This difference was statistically significant. The serum ferritin was much higher in study group (513.82 ± 505.07 ng/ml) than in the control group (88.66 ± 132.92 ng/ml). TIBC was lower (297.2 ± 100.1 μg/dl) in CKD patients with a higher TSAT values (32.2 ±15.2%) as compared to the control group. The difference was statistically significant [On analyzing the correlation of Hb with sTfR, a negative correlation was found, though this was statistically insignificant . The meanificant .The patients of CKD suffering from iron deficiency anemia may have functional or absolute iron deficiency. To differentiate between them, the patients were divided into iron replete and iron deplete groups based on TSAT<20% and ferritin < 100 ng/ml.P <0.05) [Seventy-three (71.57%) patients had sufficient iron stores as per the guidelines of NKF / DOQI. Twenty-nine (28.43%) patients had TSAT < 20% or ferritin < 100 ng/ml or both indicating depletion of iron stores. Three patients had both TSAT < 20% and ferritin < 100 ng/ml indicating absolute iron deficiency. There was a statistically significant difference in level of sTfR levels in these groups (P <0.05) .When sTfR values were correlated with iron, TIBC, TSAT and ferritin in patients with CKD and controls, no statistically significant correlations were found. The change in values of these parameters on follow up also did not show statistically significant correlation with sTfR .Many authors have used sTfR/ log ferritin ratio, sTfR F index for their analysis and given a cutoff value to diagnose iron deficiency anemia. In our study the mean of sTfR F index in cases was 1.3 (range 0.3-6.6) and in controls was 4.5 (range 1.5-15.5). It can be inferred that a ratio of >1.4 indicates co existence of iron deficiency anemia with anemia of chronic disease while ratio of up to 1.3 indicates anemia of chronic disease only.A total of 102 patients were enrolled for the study, nine patients died and one underwent renal transplantation before the completion of the study. Fifty five patients could be followed- up for 4 weeks, while only 25 patients completed the study and were followed up for the complete 6 months.The main cause of CKD in the present study was diabetes mellitus (49.02%). Agarwal in 2005 observed that in India, diabetes and hypertension were responsible for 40-50% of all cases of CKD.et al. in 2002 reported a prevalence of 94%[et al.[et al.[et al. in 1999 in Indians was 7.27 ± 1.26 g%,[et al.[et al.[The prevalence of anemia in the patients was 96.08% and the mean hemoglobin at baseline was 7.65±2.1 g%. Talwar ce of 94% while Ma4%[et al. reportedl.[et al. The mean 1.26 g%, while Br%,[et al. observedl.[et al. of 11.4 P value of < 0.01. The mean sTfR level in patients at enrolment was 3.23 ± 2.07 mg/l. The mean level of sTfR in controls was 5.16 ± 3.64 mg/l. There was no data available from India regarding the levels of sTfR in CKD patients. Being an expensive test, no work has been reported from India, the values observed by researchers in other countries were understandably different and not comparable. Fusaro et al.[et al.[On comparing the sTfR levels in controls and patients with CKD, a statistically significant difference was found, with a ro et al. observedl.[et al.On follow up of these hemodialysis-dependent CKD patients for six months, who were also receiving intravenous iron and erythropoietin, no statistically significant change in the levels of sTfR was found. Also, there was no statistically significant difference in hemoglobin levels though some improvement was seen, from 7.65±2.1 gm/dL at enrolment to 8.51± 1.88 gm/dL at 6 months. Thus, no statistically significant change in Hb and sTfR levels was observed, which is difficult to explain.et al. in 1998 reported an inverse correlation between hemoglobin and sTfR values in hemodialysis patients on recombinant erythropoietin treatment.[et al. in 2002 observed that concentration of sTfR positively correlated with hematocrit and hemoglobin.[et al. in 2001 also reported a positive correlation between hemoglobin, hematocrit and sTfR.[On studying the correlation of hemoglobin with sTfR, a negative correlation was found (r = − 0.028) which was statistically insignificant. Tonbul reatment. Chiang eμg/dl) in study group as compared to 418.10 ± 103.82μg/dl in controls. These results emphasize the limitation of these parameters to diagnose iron deficiency anemia in CRF patients as ferritin is also an acute phase reactant and TIBC a negative acute phase reactant. Uremia per se has been described as a chronic inflammatory state and these parameters can not represent the true state of iron status in these patients.[The mean values of serum ferritin, TIBC and TSAT showed statistically significant difference between cases and controls. The control group presented with the biochemical profile diagnostic of iron deficiency anemia with low ferritin and TSAT. However, in the case of the study group, ferritin levels were markedly high (515.82± 505.07 ng/ml) as compared to (88.66 ± 132.92 ng/ml) the control group. TIBC values were lower (297.2 ± 100.1patients.The levels of sTfR were lower (2.82 ± 0.98 mg /l) in iron deplete group as compared to the iron replete group(3.39 ± 2.36 mg/l) indicating that sTfR is not a good marker of IDA in CKD. Raised sTfR levels in iron replete group may be due to ongoing erythropoiesis in these patients.et al. in 2005, no correlation was found between sTfR and TSAT or between sTfR and ferritin.[In the present study no significant correlation of sTfR with iron, TIBC, ferritin or transferrin saturation was found in hemodialysis patients on follow up. Tarng and Huang in 2002 reported a significant correlation of sTfR with ferritin and transferrin saturation. However,ferritin.The role of sTfR as a marker of iron deficiency anemia in CRF patients remains doubtful. This is due to complexity of iron metabolism in these patients. They may have absolute iron deficiency as well as functional iron deficiency due to erythropoietin therapy and inadequate iron supplementation. Further, levels of sTfR can be raised in both iron deficiency and erythropoiesis.


The benefits of β-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).EBC was collected before and 30 minutes after administration of inhaled salbutamol (800 μg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) μM versus 21.21 (8.07 to 29.83) μM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).EBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaOEBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress. Collection of exhaled breath condensate (EBC) is a novel noninvasive means of obtaining lower respiratory tract samples that can be repeated several times with short intervals between sampling . The colisoPGF2α) concentration in patients with, or at risk for, ARDS as compared with normal control subjects [Several studies have reported mediator changes in EBC samples from acute respiratory distress syndrome (ARDS) patients, such as an increased hydrogen peroxide concentration  and an isubjects . A corresubjects . The EBCsubjects . In addisubjects .The potential benefits of β-adrenergic stimulation in ALI include epithelial protection, decreased neutrophil chemotaxis and activation, lower proinflammatory cytokine production, increased surfactant secretion, improved respiratory mechanics, and increased alveolar fluid clearance -9. No stThe aim of the present study was to use EBC biomarkers to investigate whether salbutamol has anti-inflammatory effects on the lungs of mechanically ventilated patients with ALI.Mechanically ventilated adult patients who met the criteria for ALI according to the American–European Consensus Conference definition  were eliThe study was approved by the local Ethics Committee and informed consent was obtained from the patients' family before inclusion.Ventilatory parameters, pulmonary gas exchange, the Lung Injury Score , and theSamples were collected before and 30 minutes after administration of inhaled salbutamol  by metered-dose inhaler . EBC was collected using a commercially available condenser , fitted with an adapter for mechanically ventilated patients . The heat and moisture exchanger was removed 1 minute before starting EBC collection. The EBC condenser cooled exhaled breath at -20°C. The collector temperature was measured at the beginning of collection. The EBC (1 to 2 ml) was collected in 25 to 45 minutes, depending on the patient's volume per minute. Samples were transferred immediately to the laboratory for processing.isoPGF2α and leukotriene B4 (LTB4), were immediately stored at -70°C, and were analyzed within 1 month after collection. The other aliquots were used to measure the conductivity and pH before and after deaeration.Each EBC sample was divided into 500 μl aliquots in two to four polypropylene tubes . The aliquots, used for the measurement of nitrites, nitrates, 8-The pH was measured in one of the aliquots immediately after deaeration with helium (350 ml/min for 10 minutes), using a model GLP 21 calibrated pH meter  with an accuracy of ± 0.01 pH. Conductivity was measured immediately after collection using a model COND 510 conductivity meter  with an accuracy of ± 1%.The nitrate/nitrite concentration was determined by a colorimetric assay based on the Griess reaction in which sample duplicates were reacted with Griess reagent  and were measured at 540 nm absorbance with a microplate reader. The assay sensitivity was 1 μM for nitrite and 2.5 μM for nitrate.isoPGF2α concentration was determined by a competitive enzyme immunoassay using a commercially available kit . The assay sensitivity was 4 pg/ml.The EBC 8-4 concentration in EBC samples was determined by a LTB4 EIA kit  after sample lyophilization and reconstitution. The assay sensitivity was 13 pg/ml.The LTBP < 0.05 (two-sided). SPSS 13.0 for Windows  was used for the statistical analyses.Descriptive statistics are expressed as the median (interquartile range). Differences between groups were analyzed by the Wilcoxon test. Spearman's rank correlation coefficient was applied to determine correlations between the various parameters studied. Significance was set at Six patients  aged 56 (46 to 76) years were studied; none were current smokers. The origin of ALI was intrapulmonary in five patients. The etiologies included pneumonia (four patients), smoke inhalation (one patient), and extrapulmonary sepsis (one patient). Before EBC collection, patients had been mechanically ventilated for 55 (37 to 76) hours, and evolution of lung injury was 58 (32 to 79) hours.2/FIO2 ratio was 133 (96 to 211) mmHg. The Sequential Organ Failure Assessment score was 9 (5.8 to 12). No significant changes were observed in the plateau pressure (27 (24 to 30) cmH2O versus 26 (21 to 29) cmH2O, P = 0.416) or in the intrinsic positive end-expiratory pressure (0.5 (0 to 2.5) cmH2O versus0.25 (0 to 0.9) cmH2O, P = 0.18) following salbutamol administration.At the time of EBC collection, the patients' Lung Injury Score was 3 (2.3 to 3.1) and the PaOPulmonary gas exchange values before and after salbutamol inhalation are summarized in Table r = -0.899, P = 0.015). A positive correlation was also found between nitrosative species and LTB4 , and between nitrosative species and 8-isoPGF2α . The tidal volume, the PaO2/FIO2 ratio, and the Lung Injury Score showed no correlations with EBC pH or biomarkers.The main results of EBC measurement are presented in Table P = 0.028). Total nitrates and LTB4 were detectable in EBC samples from all patients, whereas nitrites and 8-isoPGF2α were detectable in five patients. A tendency to decreased nitrosative species and decreased 8-isoPGF2α concentrations was observed after salbutamol inhalation (P = 0.173 and P = 0.068).Deaerated pH values were higher after salbutamol inhalation than before . The pH becomes more alkaline in the proximal airway owing to airway epithelial cell enzyme systems, ion channel activity and buffering proteins [The pH of the airway lining fluid is the result of a balance between different buffer systems and the production and release of acids and bases in the airways . In a heproteins . The norproteins .Few studies have reported EBC pH values for mechanically ventilated patients. In otherwise healthy patients undergoing lung resection for cancer, the mean EBC pH obtained using RTubes™ was 7.8 . AnotherThree essential mechanisms in ALI patients may lead to EBC acidification . Firstly2) after salbutamol inhalation were observed, which means that changes observed in the pH were not caused by changes in alveolar ventilation. In a recent study, EBC pH values were continuously monitored in mechanically ventilated patients, and EBC acidification was observed even before the clinical alteration appeared [EBC acidity is an important marker of lung inflammation, and the higher EBC pH values detected after a single dose of salbutamol in our study could be related to an anti-inflammatory effect of β-adrenergic stimulation in ALI patients. No significant changes in the partial pressure of arterial carbon dioxide (PaCOappeared . This phappeared  and asthappeared ,21, bronappeared , and othappeared ,18. To dappeared . Likewisappeared .+/K+-ATPase alveolo-capillary channel, which allows passage of water from the alveoli to the interstitium [Experimental data have shown that β-adrenergic stimulation can significantly decrease proinflammatory cytokine expression, chemokine mRNA induction, and the resultant neutrophil lung infiltrate in an animal model of endotoxin-induced ALI . More rerstitium . NeverthisoPGF2α was observed after a single dose of salbutamol. Few studies to date have used EBC in mechanically ventilated patients, particularly in ALI patients [isoPGF2α is a marker of oxidative stress [A trend towards decreased nitrosative species and 8-patients -6,18,22.patients ,6, leukopatients  and nitrpatients . Pulmonapatients . Releasepatients . The nite stress  in patiee stress . Our res4 concentration after salbutamol administration, a finding that may have been affected by the small sample size and by the fact that only single-dose administration was tested.No changes were seen in the EBC LTB4, with lyophilization being one of the methods of choice [The present study is preliminary and has some limitations related to the EBC technique and to the small size of the patient cohort. The samples obtained are extremely diluted and most biomarkers are at the low end of assay sensitivity. A potential option to overcome this problem is to increase the concentration of the samples, as was done with LTBf choice ,5,6. FurisoPGF2α concentration in patients with ALI.In summary, EBC is a novel technique that can be used to monitor ventilated patients and to assess therapeutic interventions. In the future, it may have an important role in monitoring ALI patients because it is completely noninvasive and no adverse effects have been described to date. In our small series, inhaled salbutamol significantly increased the deaerated EBC pH and showed a tendency to decrease nitrosative species and the 8-• EBC is a novel technique that can be used to monitor airspace inflammation in ventilated patients and to assess therapeutic interventions.• In ALI patients, higher EBC pH values were detected after a single dose of inhaled salbutamol, which could be related to an anti-inflammatory effect of β-adrenergic stimulation.isoPGF2α was observed after a single dose of salbutamol, suggesting that it may play a role in preventing the lipid peroxidation that occurs in ALI and ARDS patients.• A trend to decreased nitrosative species and 8-isoPGF2α = 8-isoprostane; LTB4 = leukotriene B4; PaO2/FIO2 = arterial oxygen partial pressure:fraction of inspired oxygen, ratioALI = acute lung injury; ARDS = acute respiratory distress syndrome; EBC = exhaled breath condensate; IL = interleukin; 8-The authors declare that they have no competing interests.OR conceived the study, carried out the sample collection, performed the statistical analysis and drafted the manuscript. SG-O was involved in the design of the study, carried out the EBC sample measurements and reviewed the manuscript critically for intellectual content. M-JC and XM were involved in the design of the study and reviewed the study critically for important intellectual content. MJDG reviewed the study critically for important intellectual content. JRM conceived the study, carried out the sample collection and gave the final approval to the version to be published.