Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1 receptor antagonists and their biological evaluation.

Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model.

End-stage renal disease patients on hemodialysis: a study from a tertiary care center in a developing country.

The exact number of patients with chronic renal failure requiring renal replacement therapy in developing world is not known. Unlike the developed world, most developing countries lack renal registries. This study was initiated to know demographic and clinical data of end-stage renal disease (ESRD) patients presenting to maintenance hemodialysis (MHD) at a government funded tertiary care centre in a developing country. A prospective analysis of all new ESRD patients attending to hemodialysis at our centre from 2004 to 2007 had been done. There were 237 new hemodialysis patients during a three-year period. Males were 153 and females were 84, with the mean age 44.92 years. Diabetes mellitus (31.22%) was the most common cause of ESRD. Only 29.95% of patients had education on renal replacement therapy. 65.40% patients had emergency hemodialysis. Internal jugular catheter was the most common form of vascular access at initiation of hemodialysis. Arteriovenous fistula was secured in 29.95% of patients at presentation. Catheter-related infection appeared in 13.55% of patients on catheter. The most common infection in dialysis patients was urinary tract infection (37.14%). Renal transplantation was opted by 9.7% patients and continuous ambulatory peritoneal dialysis in 20.25% and 103 (43.45%) were lost to follow up. The rest (8.86%) continued on MHD. There were 42 (17.72%) deaths over a three-year period. The present study provided the information of the practice of hemodialysis, its population characteristics and outcomes from a developing country.

Pulse cyclophospamide in severe lupus nephritis: Southern Indian experience.

To evaluate the efficacy and safety of the monthly pulse IV cyclophosphamide (IVC) therapy in patients with severe lupus nephritis, we studied 39 patients of lupus nephritis on IVC therapy between 1998 to 2002. Single monthly cyclophosphamide (0.75-1 g/m(2)) was infused intravenously with oral prednisolone (0.5 mg/kg per day) and appropriate hydration. Of the 39 patients 25 (86.2%) patients were females and 4 (13.8%) were males. Six (2%) cases had irregular follow-up and 3 patients had expired during the initial cycles and were excluded from the study. The mean age was 25.6 + 6.72 years (range 10-40 years). The mean duration of the disease from the onset to renal biopsy was 24.2 + 18.5 months. The clinical presentations included nephrotic syndrome (34.5%), acute glomerulonephritis (31.0%), Pyrexia of unknown origin (PUO) (10.3%), and rapidly progressive renal failure (6.7%). Renal insufficiency was present in 47.2% cases. Twenty-two (75.9%) patients had diffuse proliferative glomerulonephritis (class IV), 6 (20.7%) focal proliferative glomerulonephritis (class III), and one (3.4%) class Vd. After a mean follow-up of 15.8 months, out of 29 patients, 13 (44.8%) had achieved complete remission, 7 (24.1%) partial remission and 9 (31.0%) cases did not respond to the therapy. Side effects of the therapy included vomiting and nausea (100%) and hair loss during the first few doses of IVC. In addition, one case had dysfunctional uterine bleeding and two patients had avascular necrosis of femoral head. We conclude that our data indicate that IVC in severe lupus nephritis is effective in Indian patients though longer follow-up is required.

Right atrial thrombus due to internal jugular vein catheter.

Right atrial thrombus is rare complication of hemodialysis central venous catheter. Literature survey revealed 49 documentations of right atrial thrombus due to a central venous catheter. We report a 58-year-old type 2 diabetic, hypertensive, end-stage renal disease patient, who 2 months after initiation of hemodialysis through a right internal jugular vein catheter, developed clinical features suggestive of pulmonary thromboembolism. An echocardiography revealed presence of a serpentine thrombus in right atrium. The internal jugular vein catheter was removed and unfractionated heparin was initiated. At the end of 6 weeks he was symptom free. We compared conservative treatment with surgery for RAT. Conservative management with central venous catheter removal and anticoagulation therapy is not inferior to the surgery.

Pseudoaneurysm of left colic artery after Tenckhoff catheter removal, with unrecognized fungal peritonitis.

A 42-year-old continuous ambulatory peritoneal dialysis patient had presented to us with symptoms and signs of peritonitis, complicated by intestinal obstruction. On fourth day after admission, the Tenckhoff catheter was removed, as there was no response to intraperitoneal antibiotic. He developed hypotension during one of the hemodialysis sessions and was found to have low hemoglobin of 4 g/dL. Computed tomography revealed high-density fluid suggestive of fresh blood and clots in the peritoneal cavity. Conventional visceral angiogram with selective inferior mesenteric arterial cannulation revealed pseudoaneurysm arising from the descending branch of the left colic artery. An effort to embolize the pseudoaneurysm failed on 2 occasions. At laparotomy the pseudoaneurysm of the left colic artery was identified after evacuation of blood clots. The pseudoaneurysm was then excised and a lateral rent in the descending branch of left colic artery was repaired. The pus showed septate hyphae on potassium hydroxide mount. He was treated with injections of amphotericin B and oral voriconazole as the culture showed growth of Aspergillus flavus. The early fibrinous, ''easy'' flimsy adhesions formed during the initial intestinal obstruction phase might have resulted in formation of the pseudoaneurysm when the Tenckhoff catheter was removed with traction. The removal of the Tenckhoff catheter, drop in hemoglobin and distension of the abdomen were temporally so closely related that the pseudoaneurysm as a result of the traction removal of the catheter was undeniable. A controlled trial would provide firm evidence either in favor or against formal dissection for the removal of Tenckhoff catheters.

Endophthalmitis: a rare complication of arteriovenous fistula infection.

Vascular access infection is a frequent problem in patients undergoing maintenance hemodialysis. Infection of arteriovenous fistula (AVF) is less common than dialysis catheter-associated infection. Previous case reports described endophthalmitis secondary to hemodialysis catheter-related infection, but not secondary to native AVF infection. We report a rare patient of endophthalmitis as a metastatic infection of AVF cannulation site abscess. A 19-year-old girl on maintenance hemodialysis for the past 2 years has presented with a history of fever, chills, and rigor of 3-days duration and painful dimness of vision in the left eye of 1-night duration. It was followed by redness of the eye, photophobia, and ocular discharge. On examination, the patient was febrile with an abscess near cannulation site of AVF. There was no perception of light in the left eye, conjunctiva was congested, cornea was clear, hypopyon present, and pupil was mid-dilated, not reacting to light. Lens was clear. Vitreitis and exudative retinal detachment was present. Methicillin sensitive Staphylococcus aureus was isolated from blood, pus from AVF abscess and vitreous fluid. Diagnosis of endophthalmitis was confirmed by B-scan ultrasound. She was treated with both intravenous and intraocular antibiotics and drainage of pus from AVF abscess and therapeutic vitrectomy. Though arteriovenous abscess responded to sensitive antibiotics and drainage, vision has not improved much. Strict aseptic precautions during regular AVF cannulation are required. Lapses may lead to loss of vision apart from described complications like access closure, endocarditis, and osteomyelitis.

Isolated skin ulcers due to Mycobacterium tuberculosis in a renal allograft recipient.

BACKGROUND: A 27-year-old male renal allograft recipient presented to hospital with isolated skin ulcers on both lower limbs. At presentation, he also had a low-grade continuous fever, malaise and anorexia. INVESTIGATIONS: Physical examination, laboratory studies, histopathological examination of tissue biopsy samples from the ulcer edges and ulcer floor, culture of the biopsy tissue, chest radiograph, bone marrow biopsy, abdominal ultrasound, tuberculin skin test and examination of three early morning samples of gastric juice and urine for acid-fast bacilli. DIAGNOSIS: Isolated cutaneous ulcers caused by Mycobacterium tuberculosis. MANAGEMENT: Four-drug antituberculosis therapy with pyrazinamide, of loxacin, ethambutol and isoniazid.