A systematic review of Demand-based & Supply-based Interventions on continuum of maternal and child healthcare in south Asian countries

Journal of Public Health - In this study, we conduct a systematic review of literature to understand the effectiveness of interventions on continuum of maternal and child healthcare services, the...     

Clinical presentation,viral kinetics,and management of human monkeypox cases from New Delhi,India 2022

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. All five cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen (HBsAg) in one case. All the cases were mild and had a good recovery. A higher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus (MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.     

Anaesthetic management of a child with Bartter’s syndrome

We report the anaesthetic management of an eight-year-old asthmatic boy with Bartter’s syndrome who had bilateral orchidopexy with caudal epidural analgesia. Bartter’s syndrome is a rare congenital disorder characterized by hypokalaemic hypochloraemic metabolic alkalosis, hyperaldosteronism, hyperreninaemia and hyperplasia of the juxtaglomerular apparatus of the kidneys. Characteristically, although these patients are normotensive they may be hypovolaemic. They may have unstable baroreceptor responses and show marked resistance to vasopressors. Hence, fluid, acid-base and electrolyte imbalances along with haemodynamic instability pose particular problems in their anaesthetic management. Previous case reports have described the management of these patients with general anaesthesia, our patient had his orchidopexy with caudal epidural analgesia using plain bupivacaine 0.5%. The patient was haemodynamically stable throughout surgery and was comfortable with caudal analgesia as the sole anaesthetic. Hypovalaemia, acid-base status and electrolyte imbalance were treated before instituting caudal epidural analgesia. We present this case report which describes the anaesthetic considerations in the light of the pathophysiology of Bartter’s syndrome.     

A case of cerebral toxoplasmosis

A histopathologically proven case of cerebral toxoplasmosis in a young HIV positive patient has been presented. The clinical problems in management are highlighted.     

Dismal rehabilitation in predominantly type II diabetics on dialysis in Inner-City Brooklyn

AIM: In order to define their demographics and medical conditions, 218 diabetic patients undergoing hemodialysis in Brooklyn were interviewed and their charts reviewed. METHODS: Patient rehabilitation was assessed with the Karnofsky score, and the urea reduction rate as well as serum albumin and hematocrit levels evaluated adequacy of hemodialysis. RESULTS: The majority of patients (167) were African-American, 25 were Whites, 19 patients were Hispanic and 6 were Asian. One patient was a Native American. The mean age was 60.5 years (range 16-88), and the majority, 52%, were women. Rehabilitation was poor, the mean Karnofsky score being 65.1+/-20.8, and only 6% of patients were working. By linear regression, there was no difference in the Karnofsky score according to gender, age, race, type of diabetes, education, family income or hematocrit level. Only the patients' self-perception of their psyche function, or how well they thought they were doing, was significant. CONCLUSION: Further work is needed to examine the reasons for the poor rehabilitation of diabetics on dialysis in Brooklyn.     

Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II trial.

PURPOSE: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. METHODS: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. RESULTS: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. CONCLUSION: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.     

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.     

Pharmacokinetics of the hypoxic cell cytotoxic agent tirapazamine and its major bioreductive metabolites in mice and humans: retrospective analysis of a pharmacokinetically guided dose-escalation strategy in a phase I trial

 Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide; SR 259075) is a selective hypoxic cell cytotoxic agent that is bioreductively activated in tumours to a reactive-drug free radical. Preclinically the agent has been shown to possess additive and synergistic anti-tumour activity in combination with radiotherapy and chemotherapy regimens. In the present study the pharmacokinetics and metabolism of tirapazamine were investigated in mice and patients as part of pre-clinical and phase I investigations. The objectives of this work were twofold; firstly, to evaluate retrospectively the utility of a pharmacokinetically guided dose-escalation (PGDE) strategy for tirapazamine, and secondly, to investigate if pharmacologically relevant plasma concentrations could be achieved at tolerable doses. Pharmacokinetic studies for PGDE were conducted in mice at four dose levels ranging from one-tenth of the LD₁₀ to the LD₅₀. The AUC at the LD₁₀ (2932 μg ml^-1min) was used to determine a target AUC value of 1173 μg ml^-1min (equivalent to 40% of the mouse LD₁₀ AUC) for clinical studies. A phase I study to investigate the tolerance of a single i.v. infusion of tirapazamine (once every 3 weeks) was initiated with close pharmacokinetic monitoring. The starting dose (36 mg/m²) was based on toxicity data obtained in the mouse, rat and dog. Doses were escalated by increases in the volume and duration of infusion. A retrospective analysis of the pharmacokinetic and toxicity data was then made to determine the utility of a PGDE approach. The drug exhibited a steep dose-lethality relationship in mice (LD₁₀ 294 mg/m², LD₅₀ 303 mg/m²). The major gross toxicities were body-weight loss (15–20%), pilo-erection and hypoactivity at all dose levels. Sporadic ptosis and conjunctivitis were observed at doses of >300 mg/m². The plasma elimination of tirapazamine fitted a monoexponential open model, with rapid elimination from the plasma (t _1/2=36±0.65 min) occuring at the LD₁₀ dose of 294 mg/m². A 10.3-fold increase in dose resulted in a 25.0-fold increase in AUC. Clinically, doses were escalated over the range of 36–450 mg/m². Ototoxicity (tinnitus and reversible hearing loss) was dose-limiting at 450 mg/m² and the MTD was 390 mg/m² for this schedule. Pharmacokinetic analyses in patients revealed that the elimination of tirapazamine in patients was generally bi-phasic, with low inter-patient variability being found in clearance. A 12.5-fold increase in dose resulted in a 19.0-fold increase in AUC. There was good quantitative agreement in metabolite formation between mice and humans with respect to the two- and four-electron bioreductive metabolites. AUC values recorded for tirapazamine at the MTD of 390 mg/m² (range 1035–1611 μg ml^-1min) were similar to the target AUC in mice. Importantly, these levels are consistent with the levels required for radiation-dose enhancement and effective combination with cisplatin in mice. Given (a) the similarities in plasma pharmacokinetics and metabolism observed at the target AUC/MTD in mice, rats, dogs and humans, (b) the similar degree of plasma protein binding seen between species and (c) the relatively low inter-patient variability noted in drug clearance, a successful PGDE approach should have been feasible. The results also indicate that potentially therapeutic levels of tirapazamine are achievable in patients at tolerable doses. Received: 27 May 1996 / Accepted: 30 September 1996