Metronidazole: a potential therapeutic agent in paroxysmal nocturnal hemoglobinuria.
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Biomedical subjects
Publications and source records attributed to R Saxena.
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Nodular regenerative hyperplasia has not previously been reported in patients who have undergone orthotopic liver transplantation. In this report we describe the clinical, biochemical and histologic findings in nine liver transplant recipients in whom nodular regenerative hyperplasia developed between 6 and 144 mo (median, 64 mo) after transplantation. Six of the patients manifested features of portal hypertension (variceal bleeding, ascites, severe intractable peripheral edema), whereas three patients were asymptomatic at the time of diagnosis. All patients had elevated serum alkaline phosphatase (median, 269 IU; range, 159 to 1182 IU) and gamma-glutamyl transferase levels (median, 247 IU; range 104 to 1513 IU). Other liver function tests remained normal. In five patients, earlier biopsies had identified histological features of venous outflow block, consistent with azathioprine hepatotoxicity. All nine patients had been taking azathioprine up to the time of presentation. After withdrawal of azathioprine, liver function tests improved appreciably in five patients and histologic improvement was documented in four of these who underwent follow-up liver biopsies. In the remaining four patients progressive graft failure ensued and all subsequently underwent repeat liver retransplantation. At a certain stage, nodular regenerative hyperplasia, in the context of a liver graft, becomes an irreversible lesion, emphasizing the need for early identification and withdrawal of the agent.
Pippali rasayana (PR), an Ayurvedic herbal medicine, prepared from Piper longum (Pippali) and Butea monosperma (Palash), and prescribed for the treatment of chronic dysentery and worm infestations was tested for anti-giardial and immuno-stimulatory activity in mice, infected with Giardia lamblia trophozoites. It produced up to 98% recovery from the infection. The rasayana had no killing effect on the parasite in vitro. It induced significant activation of macrophages as evidenced by increased macrophage migration index (MMI) and phagocytic activity. Enhancement of host resistance could be one of the possible mechanisms contributing towards the recovery of animals from the giardial infection.
Nyctanthes arbor-tristis L. (Oleaceae), a plant widely used in the traditional medicinal systems of India, has recently been reported to possess hepatoprotective, antileishmanial, antiviral and antifungal activities. In the present study strong stimulation of antigen specific and non-specific immunity, as evidenced by increases in humoral and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) and in the macrophage migration index (MMI), has been demonstrated in mice fed with 50% ethanolic extract of seeds, flowers and leaves of this plant. Maximum activity was found in the seeds in which the active principle(s) appear to be mainly associated with lipids. In flowers and leaves, however, the major activity was found in the aqueous fraction of the 50% ethanol extract. The immunostimulant substance(s) found in N. arbor-tristis L. are likely to play a role in its antiamoebic, antileishmanial, antiviral and certain other activities.
The human CYP2D6 gene codes for the enzyme, debrisoquine 4-hydroxylase, which metabolizes over 25 therapeutically important drugs. The inability to metabolize these drugs, which results in a 'poor metabolizer' (PM) phenotype, can be attributed, in some cases, to the presence of any of three previously described mutations in the CYP2D6 gene. To identify new alleles responsible for the PM phenotype, we have examined the CYP2D6 gene from individuals whose phenotypes were not consistent with their apparent genotypes. DNA sequencing revealed a single base deletion in exon 3, T1795, resulting in a frame shift and generating a stop codon one codon after the deletion. A PCR-based test was designed for this new allele (designated CYP2D6(T)) and 236 unrelated individuals from a lung cancer case control study were tested for the presence of the CYP2D6(T) mutation. Eight unrelated individuals were found to carry the D6(T) allele. Four subjects also carry the non-functional D6(B) allele and the drug metabolism phenotypes of these four D6(B)/D6(T) individuals are consistent with the D6(T) allele being responsible for reduced debrisoquine 4-hydroxylase activity. The frequency of the D6(T) allele among Caucasian controls of the case-control study was 1.8% (4/220 chromosomes).
In the pre- and postnatal period of kidney development, proliferation with subsequent functional maturation of intrinsic glomerular mesangial cells (MCs) continues within the existing framework. Recent work has suggested that PKC beta isoform is responsible for the proliferation observed during maturation. We sought to ascertain whether PKC beta isoform expression is altered during the development of the mesangium. MCs were subcultured from glomerular explants of Sprague-Dawley rat kidneys, days 1, 3, 5, 8, 15 postnatally, and adult. MCs from rat kidneys postnatally days 1-5 proliferated at a significantly greater rate than adult [ > 1.169-fold, P < 0.01] but term day 8 cells did not [ < 1.34-fold, not significant)] as assessed by [3H]thymidine incorporation. Western blot analysis using isoform specific antibodies was performed on confluent neonatal and adult MC. We observed that all neonatal and adult MC express beta I PKC (n = 8 kidneys from separate primaries for each date and adult). However, unlike adult MCs, neonatal MC express beta II in postnatal days 1-5 and none thereafter. Immunofluorescent staining of postnatal kidneys confirmed that PKC beta II is present in neonatal MC up to day 5. By day 8, staining of mesangium with PKC beta II begins to disappear and assumes a parietal epithelial pattern. In adult kidneys, there was only PKC beta II staining of the parietal epithelial cells. Our results demonstrate that differential expression of PKC beta II closely parallels the proliferative behavior of the MCs of the maturing glomerulus. Therefore, PKC beta II expression and activation may play a critical role in development.
We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.
One hundred and ten patients with common bile duct (CBD) stones were treated in the Department of Surgical Gastroenterology at SGPGIMS, Lucknow, India between January 1989 and December 1992. The primary modality of treatment was surgery in 62 patients (group I) and endoscopic sphincterotomy (ES) in 48 (group II). The two groups were well matched with respect to clinical features and presence of medical risk factors. Surgical clearance of CBD stones was achieved in 58 patients (93.5%; group Ia). Four patients (7%) had retained stones following surgery (group Ib). In group II, the CBD was cleared by endoscopic means in 20 out of 48 patients (42%) and was categorized into group IIa. In the remaining patients ES was followed by CBD exploration (group IIb). Significantly higher morbidity was seen in patients needing CBD surgery following attempted endoscopic clearance, because of ES-related complications, such as bleeding, cholangitis, septicaemia and numerous others. Use of ES to treat CBD stones on a routine basis was therefore not found to be any better than one-time surgical exploration.
OBJECTIVES: To further evaluate the association of anti-entactin antibodies with clinical manifestations in patients with systemic lupus erythematosus (SLE) and related disorders. METHODS: Sera were analysed for anti-entactin antibodies from 79 patients with SLE, 38 patients with rheumatoid arthritis, 20 patients with progressive systemic sclerosis and five with Behçet's syndrome. Sera from 150 healthy blood donors and 20 patients with pneumonia were analysed as controls. To study the association of anti-entactin antibodies with severity and activity in SLE, 30 patients were assigned into three groups with 10 patients in each: (1) with mild manifestations; (2) severe disease without renal involvement and (3) frank lupus nephritis. Two blood samples from each patient were analysed, one from the active and the other from the inactive phase of the disease. Additionally, serial sera from 12 patients with SLE were also analysed. RESULTS: Thirty one patients with SLE (39%) had IgG, IgM or both anti-entactin antibodies. Twenty three of these patients (29%) had biopsy verified glomerulonephritis and 12 (50%) were positive for anti-entactin antibodies. Of the remaining 56 patients without apparent renal involvement, 18 (36%) were positive for anti-entactin antibodies. (chi squared = 2.77, p > 0.05). With the exception of rheumatoid arthritis where six patients (24%) had IgM anti-entactin antibodies, the antibodies were present much less frequently in other diseases (two patients with systemic vasculitis whilst none of the patients with PSS or Behçet's syndrome). Only one patient with pneumonia and none of the 150 sera from healthy blood donors had anti-entactin antibodies. Among Group 1, three (30%) were positive for IgG or IgM anti-entactin antibodies. Six (60%) patients in group 2, and five patients (50%) in group 3 were positive for anti-entactin antibodies. However, the difference between the presence of anti-entactin antibodies between group 1 and 2 or between group 1 and 3 was not significant (p = 0.15 and 0.19 respectively). There was no significant correlation between the titres of anti-entactin antibodies and total serum concentration of IgG (r = 0.141, p > 0.10) and IgM. (r = 0.130, p > 0.10). Furthermore, no significant correlation was observed between SLE disease activity index (SLEDAI) scores and the titres of IgG (r = 0.067, p > 0.10) or IgM (r = -0.033, p > 0.10) anti-entactin antibodies. CONCLUSION: The study demonstrates that anti-entactin antibodies are present in a significant number of patients with SLE and tend to be more common in those with severe disease, with or without nephritis, than in patients with mild disease manifestations. There is no correlation between the titre of anti-entactin antibodies and severity or activity of SLE.
The results of bile salt treatment in patients with radiolucent stones and a functioning gall bladder have been poor. In 42 of these patients awaiting cholecystectomy we determined the value of duodenal bile examination in predicting gall stone composition, and thus identifying those less likely to respond to bile salt therapy. Based on chemical analysis and scanning electron microscopy, 28 of 42 (67%) gall stones retrieved at surgery were potentially insoluble. Microscopic examination of duodenal bile correctly identified 21 (75%) of them: it predicted all four (100%) pigment stones, three of six (50%) calcium carbonate containing cholesterol stones, and 14 of 18 (78%) cholesterol stones with pigment shells. It was nearly as reliable as microscopic examination of bile aspirated directly from the gall bladder during surgery (21 (75%) v 23 (82%); p = NS). Furthermore, the presence of cholesterol crystals in duodenal bile was a more sensitive indicator than chemical detection of supersaturation (34 of 38 (89%) v 25 of 35 (71%); p < 0.05) for prediction of cholesterol gall stones. Microscopic examination of duodenal bile, if used as a screening test, could help to exclude potential non-responders and thereby improve considerably the results of oral bile salt treatment for gall stone dissolution.
One-hundred-and-forty-five cases of malignant obstructive jaundice were seen from January 1989-December 1992. Carcinoma gallbladder (74/145) and carcinoma pancreas (67/145) were the two common causes. Fifty patients underwent a palliative surgical biliary bypass procedure. Jaundice was present in all the patients. Pruritus (40/50), cholangitis (17/50) and gastric outlet obstruction (11/50) were the other predominant symptoms which required palliation. Surgical palliation was achieved with a morbidity and mortality of 38% and 8%, respectively. Jaundice, pruritus and cholangitis were relieved in 92%, 88% and 88%, respectively. All patients with gastric outlet obstruction had complete relief. The mean hospital stay was 18.5 days. The mean survival was 6.5 months and 8.6 months for carcinoma gallbladder and carcinoma pancreas, respectively.
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