Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.     

Spilled Gallstones: the Source of an Enigma

Spillage of gallstones may occur in the course of laparoscopic cholecystectomy. The incidence of this mishap and its consequences are variable. Ignored by many surgeons, stone spillage may be the source of significant morbidity many years after surgery. In this report, we describe the clinical course of a patient who presented with upper abdominal pain and swelling. The past history was positive for laparoscopic cholecystectomy 15 years earlier. After excision, the swelling was found to be a pseudocyst formed around spilled gallstones during a previous cholecystectomy. Apart from postoperative wound infection, the patient recovered well and remains so. Here, we discuss the problem and provide suggestions for spillage prevention and stone retrieval once spillage occurs.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Detection of low birth-weight new born babies by anthropometric measurements in Bangladesh

Birthweight is an important indicator of child survival. Appropriate and timely care of a newborn specially if he is born with low birthweight is important but this is difficult in developing countries since most of the deliveries are conducted at home where adequate facilities to weigh a new born does not exist. This study was conducted to find out a surrogate which could efficiently be used for detecting low birthweight babies at birth when no weighing machine is around. In this study 41% of the newborn babies were found to weigh less than 2,500 gm at birth. Out of this about 52% were females. The mean chest, thigh and mid-arm circumference at birth for males were 30.89 cm, 15.06 cm and 9.27 cm respectively with standard deviations of 1.83 cm, 1.30 cm and 1.04 cm. Corresponding figures for female babies were 30.69 cm, 15.14 cm and 9.25 cm respectively with standard deviations of 2.08 cm, 1.70 cm and 1.16 cm. Correlation co-efficient between normal birthweight and the chest, thigh and mid-arm circumference were 0.867, 0.845 and 0.842 respectively. A liner regression analysis showed that a chest circumference of 30.14 cm, a thigh circumference of 14.56 cm and a mid-arm circumference of 8.90 cm corresponded well with a birthweight of 2,500 gm. On this basis sensitivity, specificity and predictive values of the chest circumference was better than the other two measurements. However, the mid-arm circumference was observed to be more reliable than the other two measurements for detecting birthweight less than 2,000 gm. A home made measuring tape has been devised on this basis to detect brithweights with cut-off values for 2,500 gm, 2,000 gm to 2,500 gm and 2,000 gm in different shades of colour for illiterate birth attendants.     

Relapsing polychondritis presenting with stridor from bilateral vocal cord palsy.

A case of bilateral vocal cord palsy caused by relapsing polychondritis is presented. The diagnosis was not suspected preoperatively and was made solely on histopathology. A case is made for histological examination of cartilage removed during routine tracheostomy.     

Comparison of the interaction of agmatine and crude methanolic extracts of bovine lung and brain with alpha 2-adrenoceptor binding sites.

1. In the present study we have evaluated whether alpha 2-adrenoceptor binding sites on bovine cerebral cortex membranes labelled by [3H]-clonidine, [3H]-idazoxan and [3H]-RX-821002 can distinguish between known agonists and antagonists. This model has then been used to compare the binding profiles of the putative non-catecholamine, clonidine-displacing substance (CDS), agmatine and crude methanolic extracts of bovine lung and brain. 2. Saturation studies carried out in the presence and absence of noradrenaline, 10 mumol 1(-1), revealed that the maximum number of binding sites on bovine cerebral cortex membranes for [3H]-idazoxan and [3H]-RX-821002 were approximately 60-80% greater than those for [3H]-clonidine (62.6 fmol mg-1 protein). Rauwolscine, the selective alpha 2-adrenoceptor antagonist, was approximately 100 fold more potent against each of the ligands than the selective alpha 1-adrenoceptor diastereoisomer, corynanthine. Also, the pKi value for the selective alpha 1-adrenoceptor prazosin against each ligand was less than 6. 3. Adrenaline, UK-14034, rauwolscine, corynanthine, RX-811059 and prazosin produced concentration-dependent inhibition of binding of all three 3H-ligands. The agonists, adrenaline and UK-14304, were approximately 5 and 10 fold less potent against [3H]-idazoxan and [3H]-RX-821002, respectively, than against [3H]-clonidine. In marked contrast, the antagonists, rauwolscine, corynanthine, RX-811059 and prazosin exhibited a different profile, being approximately 2-3 fold more potent against sites labelled by [3H]-RX-821002 and [3H]-idazoxan compared to sites labelled by [3H]-clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is spironolactone safe for dialysis patients?

BACKGROUND: Spironolactone is useful in heart failure, but is not given to dialysis patients for fear of hyperkalaemia. This study evaluated the safety of spironolactone administration in haemodialysis patients. METHODS: Fifteen haemodialysis outpatients with mean serum potassium <5.6 mEq/l over the preceding 4 months were treated with spironolactone 25 mg daily for 28 days. Serum potassium was measured before every haemodialysis during the study. Aldosterone and renin were measured at the beginning and end of the study. Patients were monitored for side effects. Data were examined with a paired t-test, with patients serving as their own controls and P < 0.05 considered significant. A sample size of 14 was required to achieve a power of 0.8 and a P = 0.05 to detect a potassium difference of 0.5 +/- 0.6 mEq/l. All patients were analysed as intention-to-treat. RESULTS: The mean potassium level was 4.6 +/- 0.6 mEq/l at baseline and 4.9 +/- 0.9 mEq/l at study completion (P = 0.14). Thirteen patients completed the trial with no potassium levels >6.0 mEq/l. Four patients had potassium levels between 5.5 and 6.0 mEq/l. One patient was withdrawn at day 20 after developing hyperkalaemia (7.6 mEq/l). Another patient was withdrawn at day 25 after missing a dialysis treatment. There were no differences in either baseline or 28 day aldosterone or renin levels (16.8 +/- 28.8 vs 11.7 +/- 6.1 ng/dl and 3.5 +/- 3.9 vs 3.5 +/- 3.5 ng/ml/h, respectively). Infrequent side effects included dry mouth, nosebleed, pruritis, gynecomastia and diarrhoea. No significant leukopenia or anaemia was noted. CONCLUSIONS: Spironolactone may be considered as a treatment option for selected chronic haemodialysis patients with heart disease.