Intermediate care and diversity: principles and practice.
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Biomedical subjects
Publications and source records attributed to I Singh.
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OBJECTIVE: To determine the quality, and especially the dissolution properties of rifampicin, of fixed-dose combination (FDC) formulations of anti-tuberculosis agents manufactured by major market holders in the anti-tuberculosis sector and supplied for use in national tuberculosis control programmes. METHODS: Dissolution studies were performed for four formulations supplied by four different manufacturers in four dissolution media (0.1N and 0.01N HCl, phosphate buffer [PB] and 20% vegetable oil in PB), at four different agitation rates using USP apparatus II. The formulations were subjected to 4-week accelerated stability studies (40 degrees C / 75% RH) and evaluated for physical, chemical and dissolution stability. RESULTS: The formulations tested complied with pharmacopeial quality control (QC) tests. The extent of rifampicin release was independent of dissolution medium; however, a slight decrease in the dissolution rate was observed in two products. More than 75% of drug was released in 45 min at all agitation intensities except 30 rpm, and 20% oil in the medium reflected fed state. Formulations were stable in the packaging conditions recommended by the manufacturer for at least 4 weeks. CONCLUSIONS: The formulations tested passed the QC tests and were found to be stable. A decrease in the rate, although not the extent, of dissolution necessitated multiple point dissolution in gastric and intestinal pH conditions to ensure consistency in in vivo bioavailability.
BACKGROUND: Monocytes may have an important role in the resolution of venous thrombosis. Increased expression of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) is associated with an ingress of monocytes into the thrombus. This study was designed to evaluate the importance of these activators in thrombus resolution. METHODS AND RESULTS: Inferior caval vein thrombosis was induced in cohorts of adult wild-type, uPA gene-knockout (uPA-/-), and tPA gene-knockout (tPA-/-) mice in a flow model. Thrombi were harvested from wild-type and uPA-/- mice (n=60 per group) between 1 and 60 days. Thrombi were also obtained from groups of wild-type and tPA-/- mice (n=24 per group) between 1 and 28 days. Thrombus size and macrophage content were measured by computer-assisted image analysis. Thrombus resolution was significantly impaired in the uPA-/- mice compared with wild-type controls (P<0.0001) but was unaffected in tPA-/- mice. Monocyte content in wild-type mice was highest at 14 days after thrombus induction and was approximately 4 times greater than in uPA-/- mice (P=0.0043). Thrombus size in uPA-/- mice transplanted with wild-type marrow (0.29+/-0.06 mm2) was significantly smaller than in uPA-/- mice given uPA-/- bone marrow (3.9+/-1.1 mm2) (P=0.0022). Donor bone marrow-derived cells expressing LacZ were present in the thrombus after transplantation. CONCLUSIONS: The resolution of experimental venous thrombus is dependent on uPA but is unaffected by the absence of tPA. Absence of uPA is also associated with delayed monocyte recruitment into the thrombus. Transplanting wild-type bone marrow restores thrombus resolution in uPA-/- animals, suggesting an important role for bone marrow-derived cells in this process.
Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia - 8 and oligoasthenospermia - 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (approximately 5%) is much lower than the frequency (approximately 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.
A case of tubercular osteomyelitis of zygoma is reported. It is difficult to diagnose because of its rarity unless a high index of suspicion is kept in mind more so in an endemic area.
The rapid engulfment of apoptotic cells is a specialized innate immune response used by organisms to remove apoptotic cells. In mammals, several receptors that recognize apoptotic cells have been identified. Previous analysis of the engulfment gene ced-6 in Caenorhabditis elegans (C. elegans) has suggested that CED-6 is an adapter protein that participates in signal transduction pathway that mediates the specific recognition and engulfment of apoptotic cells. Here, we describe our isolation and partial characterization of a mouse cDNA, which is like an orthologue of C. elegans CED-6. PCR screening of mouse cDNA pool with primers designed from the C. elegans CED-6 cDNA sequence resulted in about 300 bp PCR product which was partially sequenced and then screened to a mouse full-length cDNA library. Thus in this study we report the identification of a novel C. elegans CED-6-like orthologue in mouse, which has probable apoptotic like function.
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Mesonephric or mesonephroid adenocarcinoma of the bladder may be a malignant form of nephrogenic adenoma or nephroid metaplasia. The lesion is rare, and to the best of our knowledge only 9 cases have been reported in the world literature. We report another case of mesonephroid adenocarcinoma of the bladder and urethra which was treated with transurethral resection and subsequent chemotherapy.
The authors describe two patients with leiomyoma of the bladder who presented with bladder outlet obstruction. The results of magnetic resonance imaging are presented and their management discussed. Complete resection was curative in both patients, by enucleation in the first case and by transurethral resection in the second.
A key issue in health provision is the approach to health inequalities. In the UK, black and ethnic minority populations are disadvantaged in this respect. We obtained annual/public health reports from 13 health authorities (HAs) and 22 primary care trusts/groups (PCT/Gs) serving conurbations with large black and ethnic minority populations, and examined them for mention of special health issues for these groups and the action being taken. 22 of the 35 reports referred to such issues but only 17 referred to special initiatives; the most frequently mentioned were diabetes and coronary heart disease. We recommend that HAs and PCT/Gs serving large black and ethnic minority populations state specifically in their annual reports their awareness of health-equality issues and the action being taken to address them.
Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.
Mononuclear cell infiltration into the CNS and induction of inflammatory cytokines and iNOS in diseases like multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) have been implicated in subsequent disease pathogenesis and progression. We report that Lovastatin treatment blocks the clinical disease and induction of inflammatory cytokines and iNOS in spinal cords of MBP induced EAE rats. A significant number of the infiltrating cells in CNS were ED1+ cells of monocyte/macrophage lineage. To understand the mechanism of efficacy of Lovastatin against EAE, we examined the effect of Lovastatin on the transmigration of mononuclear cells into EAE spinal cord. The data presented here documents that Lovastatin treatment attenuates the transmigration of mononuclear cells possibly by down regulating the expression of LFA-1, a ligand for ICAM, in endothelial-leukocyte interaction. These results indicate that Lovastatin treatment prevents infiltration by mononuclear cells into the CNS of rats induced for EAE, thereby lessening the histological changes and clinical signs and thus ameliorating the disease. These observations indicate that Lovastatin treatment may be of therapeutic value against inflammatory disease process associated with infiltration of activated mononuclear cells into the tissue.
A survey of health authorities and primary care groups with high ethnic minority populations in England showed HAs were further advanced in addressing the special needs of ethnic minorities than PCGs. More than three-quarters of HAs cited initiatives for ethnic minorities compared with only 36 per cent of PCGs. Only a minority of organisations reported schemes to address health inequalities. Commissioning organisations covering large communities of people from ethnic minorities should do more to address their special health needs.
A rare case of congenital malformation of the nose that was successfully corrected surgically is reported.
Minimal inhibitory concentrations (MICs) of five antibiotics namely amikacin, gentamicin, tetracycline, ciprofloxacin, and nitrofurantoin for pork isolates of Yersinia enterocolitica increased two- to eightfold after bacteria were grown in the presence of 5 mm arsenite. For Y. enterocolitica isolates obtained from wastewater (sewage effluents), an unequivocal increase in MICs was seen with amikacin and gentamicin. No change was discernible in the outer-membrane proteins after isolates were grown in the presence of arsenite.
OBJECTIVES: The efficacy, safety, feasibility, and outcome of in situ treatment applied to select proximal ureteral calculi was assessed and analyzed with a view to avoiding auxiliary interventions and providing high clearance rates in the shortest possible time. We studied the impact of several clinically important variables, including power index, degree of hydroureteronephrosis (HDUN), stone size, and composition on the efficacy of sequential in situ boosted extracorporeal shock wave lithotripsy (ESWL) in a select group. The power index requirement for the in situ boosted protocol and the impact of the stone size/composition, degree of HDUN, and clearance rates were also analyzed. METHODS: An in situ (no instrumentation) boosted protocol was applied to 130 primary unimpacted proximal ureteral calculi with no prior intervention. A typical session with the Siemens Lithostar Plus comprised 3000 shock waves, in installments of 500, deployed at a power setting of 1 to 4 kV with a gradual stepwise escalation. Sequential boosted additional sessions of ESWL were administered on days 2, 7, and 14, tailored to the degree of fragmentation, clearance status, and amount of residual stone bulk. Several parameters (shock waves, kilovolts used, fluoroscopy time, number of sessions, stone size, composition, fragmentation, clearance, and HDUN) were recorded and the results analyzed statistically. RESULTS: The results were excellent in 83.8%, with a mean duration to complete clearance of 11.3 days. In situ ESWL failed in 7.69%, and the auxiliary intervention rate was 10.7%. Pre-ESWL HDUN was present in 78.3%, the mean power index was 184.6/session/case, and the average stone burden was 8.9 mm(2). Calcium oxalate monohydrate was the most common stone (56%). Renal colic was the most common side effect observed. The power index, fragmentation at the first session, and stone size were found to be the most favorable significant variables affecting stone clearance. The degree of HDUN, number of sessions, and stone composition did not significantly impact the clearance rates. CONCLUSIONS: In situ boosted ESWL should be the first-line therapeutic modality in select unimpacted primary proximal ureteral stones.
OBJECTIVES: To review the management of heavily encrusted and stuck JJ ureteral stents. We report our experience and review current published reports in managing heavily encrusted and stuck JJ stents, the guidelines for management, and the prevention of such problems. METHODS: We reviewed our stent records from January 1994 to December 2000 and analyzed our stent complications and their final outcome. Fifteen patients had heavily encrusted and stuck stents. Of these, 14 were encountered in patients with a sizable stone burden (400 to 650 mm(2)) and 1 occurred in a patient with malignant ureteral obstruction. Sandwich combinations of multiple extracorporeal shock wave lithotripsy/traction and endourologic procedures were used to render them stone and stent free. The stent was examined and the encrustation was analyzed by x-ray crystallography. RESULTS: Of 15 patients, 13 were available for evaluations; 1 patient was lost to follow-up and 1 patient died. The average stone burden was 625 mm(2). The encrustation was localized to the upper end in eight and to the lower and upper end in three. In 4 cases, the entire stent was encrusted, and the lumen was occluded in 12. All 13 patients with stuck, fragmented, and encrusted stents were rendered stone and stent free; 2 of the 13 had clinically insignificant residual stones (less than 2 mm). Calcium phosphate and monohydrate stones were the most commonly encountered stone encrustations. CONCLUSIONS: Stent encrustation is one of the most serious complications of polyurethane JJ stents. Multimodal endourology should form the cornerstone of therapy for heavily encrusted stuck stents. It is important to maintain an efficient computerized stent log under the direct supervision of a physician. Patients with probable risk factors should be monitored even more frequently to avoid mishaps and morbidity.
The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates cells through a family of G-protein-coupled EDG receptors. The present article examines the role of lipid phosphate phosphatase-1 (LPP-1, or phosphatidate phosphate 2A) in regulating cell activation by LPA. Overexpressing LPP-1 approximately doubled the rate of dephosphorylation of exogenous LPA by Rat2 fibroblasts. The amount of LPA dephosphorylation was restricted to less than 10% of the total exogenous LPA. Over-expression of LPP-1 attenuated cell activation as indicated by diminished responses including cAMP, Ca2+, activation of phospholipase D and ERK, DNA synthesis and cell division. LPP-1 therefore provides a novel level of regulation for controlling cell signalling by exogenous LPA.