Search PubMed⌕ Search

Biomedical subjects

H Shah

Publications and source records attributed to H Shah.

At least 55 records · Page 3Linked to original sources
PubMed1998

Systematic development of a block copolymer adjuvant for trivalent influenza virus vaccine.

The current influenza virus vaccines induce systemic humoral immunity and short lived cellular immunity in young adults. Unfortunately these vaccines are only 50% efficacious in the elderly (> 65 years) and high risk groups of the very young. The use of a vaccine adjuvant to correct this deficit would therefore be very beneficial to these population groups. We have developed high molecular weight synthetic non-ionic block copolymers with adjuvant activity. These copolymers are compatible with, and active in, aqueous, physiological formulations in which they spontaneously assemble into 500-3000 nm particles. By varying both the molecular weight and the proportions of hydrophilic and hydrophobic components of the molecule, we have designed the optimal copolymer adjuvant for use with influenza hemagglutinin. This copolymer, termed CRL-1005, was investigated for its ability to augment the immune response of mice to the commercially-available human influenza vaccine, Fluogen. Co-formulation of CRL-1005 with the vaccine resulted in markedly increased antibody titres measured by both ELISA and the functional haemagglutination inhibition assay, indicating that critical immunogen epitopes were not destroyed. A single dose of copolymer and vaccine produced both long term rising antibody titres (six months) and primed for a potent secondary response. This high molecular weight copolymer is non-toxic and should therefore be well suited for widespread use.

Adjuvants, Immunologic↗
PubMed1997

Outcome of tunneled hemodialysis catheters placed via the right internal jugular vein by interventional radiologists.

PURPOSE: To assess the outcome of interventional radiologic placement of tunneled hemodialysis catheters via the right internal jugular vein. MATERIALS AND METHODS: In 194 patients, the catheter was placed via the right internal jugular vein unless thrombosis was present. Real-time ultrasound-guided puncture and fluoroscopic guidance were used. Patients were followed up until catheter removal or death. Outcomes evaluated included infection, thrombosis, and catheter malfunction. RESULTS: In 175 patients, 250 consecutive catheters were placed via the right internal jugular vein with 100% success. All catheters functioned immediately after placement. Procedural complications were limited to clinically unimportant air embolus (n = 2). No instances of pneumothorax, hemothorax, or substantial bleeding complications occurred. Follow-up was available in 173 (99%) patients. Mean and median "catheter duration" were 87 and 56 days, respectively. Catheter-related symptomatic venous thrombosis or stenosis was not observed. The rate of infection was 0.08 per 100 catheter days, and the rate of malfunction that necessitated removal was 0.22 per 100 catheter days. Definite or possible catheter thrombosis that necessitated removal occurred at a rate of 0.16 per 100 catheter days. CONCLUSION: Interventional radiologic placement of tunneled hemodialysis catheters via the right internal jugular vein showed equal or better long-term results than those reported for surgical placement. Interventional radiologic placement should be the method of choice.

Catheterization↗
PubMed1996

Reversal of multi-drug resistance in vitro by fatty acid-PEG-fatty acid diesters.

Fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, that modulate multi-drug resistance (MDR) have been described; however, the drug potential of these preparations is unclear because of the molecular heterogeneity of these and other commercial surfactants. In previous experiments, an active but still polydisperse preparation, designated CRL 1337, was synthesized by reacting purified oleic acid with a 20-fold molar excess of ethylene oxide. We have subjected this preparation to chromatographic separation, and infrared analysis of the active fractions revealed a significant component of diester structures (fatty acid-PEG-fatty acid). A new generation of diester compounds has now been synthesized. Preparations comprised of 99% diesters were significantly more potent than monoester preparations for MDR modification activity in vitro. As previously determined for ethylene oxide-derived preparations similar to CRL 1337, the nature of the fatty acid domains proved to be important for activity, as was the relative length of the polyethylene glycol domain (which determines the hydrophile-lipophile balance). The ester linkage appeared unimportant since homologous diethers and diamides had activity similar to that of diesters. Stearic acid diester was 1.5- to 7-fold more potent than CRL 1337 when tested in cell proliferation inhibition assays. In light of these structural restrictions on drug potentiation, and since these surfactants are active at relatively low concentrations (below 1 microgram/ml), investigations of their mechanism of action were initiated by exploring specific interactions with P-glycoprotein. Both active and inactive diesters inhibited azidopine labeling of P-glycoprotein, suggesting that fatty acid-PEG diesters can interfere with P-glycoprotein substrate binding. Other attributes of these preparations must contribute to their ability to reverse MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Influence of CD26 and integrins on the antigen sensitivity of human memory T cells.

The antigen sensitivity of class II MHC restricted human CD4 T-cell clones is demonstrated to increase gradually with time after restimulation. This is manifested in a requirement of less antigen in culture, as well as decreased numbers of peptide-MHC complexes per APC for T-cell activation, and in an increased resistance to inhibition by class II MHC blockade. The increase in antigen sensitivity is accompanied by increased cell-surface expression of CD26, LFA-1, and VLA-1, whereas the expression of TCR and a series of other cell-surface molecules remains unchanged. Using appropriate monoclonal antibodies, we have shown that CD26 and LFA-1 contribute directly to the increased antigen sensitivity of "late-stage" T-cell clones. The late-memory T-cell phenotype established in this study is shown to occur also among T cells activated in vivo. We suggest that increasing the antigen sensitivity via antigen-nonspecific molecules is a physiologic mechanism for maintaining T-cell memory in face of decreasing antigen concentration, and for ensuring preferential activation of memory T cells upon repeated encounter with antigen.

Antigen Presentation↗
PubMed1996

Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis?

BACKGROUND: Hepatitis E virus, which is endemic in our region, can cause severe liver dysfunction in pregnant women and this can be clinically confused with acute fatty liver of pregnancy. METHODS: We studied the clinical and laboratory data as well as the maternal and fetal outcomes of 12 pregnant women presenting with fulminant hepatic failure in order to determine the etiology of the disease. The clinical diagnoses were subsequently correlated with serologic assays for acute HEV infection. All patients were severely ill with deep jaundice, grade 3-4 encephalopathy and abnormal prothrombin times. RESULTS: A clinical diagnosis of acute viral hepatitis was made in nine patients and of acute fatty liver in the other three cases. IgM and IgG antibodies confirmed acute viral hepatitis E in six of the nine patients while one had acute hepatitis A infection. HEV IgM and IgG antibodies were, however, also positive in two of the three patients thought to have acute fatty liver. Maternal and fetal mortality were 16.6% and 50%, respectively. CONCLUSIONS: We conclude that hepatitis E is the usual cause of acute liver failure in our pregnant women and that clinical and laboratory features do not permit accurate distinction between acute HEV infection and acute fatty liver of pregnancy. The prognosis in patients with acute HEV infection is much better than in other groups with severe liver failure (mortality 16% vs 68%).

Acute Disease↗
PubMed1996

Community acquired and post-transfusion hepatitis C "is there a difference?".

We analyzed 77 consecutive hepatitis C antibody positive patients to compare the history, laboratory data and histological features of community acquired (CA) and post-transfusion (PT) hepatitis C. Forty-six patients had "CA" and 31 "PT" hepatitis C. Mean age in both groups was same (45.67 vs 46 years). Male to female ratio was 2:1 in the CA group and 1:2.4 in the PT group. Mean duration between jaundice and first presentation was 8.9 years in the CA group and the mean duration between transfusion and first presentation was 9.8 years in PT group. No significant difference was found between two groups in the laboratory data. Liver biopsy was done in 32 patients (19 CA and 13 PT group). Mean histological score for disease activity was 9.3 in both groups, although more (68%) patients in the CA group had cirrhosis with chronic active hepatitis, (CAH) as compared to the PT (54%) group. Hepatitis C is an important cause of CA hepatitis. PT hepatitis C is more common in females because of increased likelihood of receiving transfusion for obstetric and gynaecological reasons. There is no significant difference in the laboratory and histological features between CA and PT hepatitis C.

Adult↗
PubMed1995

Self tolerance to T cell receptor V beta sequences.

T cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V beta 8.1 and V beta 8.2 TCR proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V beta protein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks.

Amino Acid Sequence↗
PubMed1995

Mycoses of the breast: diagnosis by fine-needle aspiration.

Fungal infections of the breast are unusual and may clinically mimic carcinoma. When studied by fine-needle aspiration (FNA), such masses may yield necrosis, granulomatous inflammation, reactive histiocytes, and atypical epithelial cells. Cohesive groups of atypical epithelial cells featured nuclear enlargement and overlapping, as well as prominent nucleoli. The organisms may be widely scattered, so that careful evaluation was required for their identification. In concert with provocative clinical findings, these features may lead to an erroneous diagnosis of malignancy. We describe three women with mycotic masses of the breast initially studied by FNA. The first patient presented at age 31 with a large, firm breast mass, chest wall extension, and radiographic evidence of vertebral bone involvement. FNA was requested to confirm the clinical diagnosis of advanced breast carcinoma. In addition to the atypia described above, the smears showed yeast forms indicative of blastomycosis surrounded by neutrophils. She remains well, following antifungal treatment. The second case of Blastomycosis was diagnosed by FNA of a breast mass in a 64-yr-old woman, who also responded to treatment. The third patient's preoperative needle aspiration showed granulomas, but no organisms were identified, even with special stains; silver stains of surgically excised tissue showed histoplasmosis.

Adult↗
PubMed1995

A retrospective review of cases of anaerobic empyema and update of bacteriology.

We conducted a retrospective study to update the bacteriology of 46 cases of anaerobic empyema that were originally studied between 1976 and 1993 at the Wadsworth Anaerobic Bacteriology Clinical Research Laboratory (Los Angeles). Anaerobic bacteriologic studies were completed for all 46 pleural fluid specimens, and aerobic bacteriologic studies were completed for 41 of these specimens. Thirty-seven clinical charts were available for review. A total of 161 anaerobic isolates (3.5 per patient) representing 64 species or groups were recovered. The most common isolates were as follows: Fusobacterium nucleatum (19); Prevotella oris-buccae group (13, 9 of which were P. oris); Bacteroides fragilis group (11, 4 of which were B. fragilis); pigmented Prevotella species (17, 8 of which were in the Prevotella intermedia-nigrescens group); Peptostreptococcus species (17, 9 of which were Peptostreptococcus micros); Eubacterium species (7); Lactobacillus species (8); Actinomyces species (7); and Clostridium species (7). Nineteen if the cases were of purely anaerobic etiology; of these, eight were caused by a single organism: F. nucleatum (five cases); B. fragilis (two cases); and Prevotella mangus (one case). Of the 45 aerobic isolates (1.1 per patient), viridans streptococci were most common (21 isolates), followed by group D nonenterococcal streptococcus (four isolates). Only nine gram-negative rods (six enteric and three nonenteric organisms) and one Staphylococcus aureus isolate were recovered. The susceptibility to penicillin of 64 isolates was examined with the use of the spiral gradient method; 21 (33%) of these isolates were beta-lactamase positive (MICs ranged from 1.1 to > or = 54 micrograms/mL vs < or = 0.27 micrograms/mL for beta-lactamase-negative strains).

Adult↗
PubMed1995

Benign tumors of the tracheobronchial tree. Endoscopic characteristics and role of laser resection.

We conducted a review of all the bronchoscopies performed at our institutions for benign tumors from 1980 to 1991 to determine the endoscopic characteristics of these lesions. We reviewed the charts, the endoscopic characteristics from our video records, and finally the pathologic findings of these cases. We tried to identify the effectiveness of laser resections in each group. Of a total of 3,937 patients, 185 (4.7%) were benign tumors. On these patients, 317 procedures were carried out. There were 3 myoblastomas, 53 papillomas, 1 adenoma, 8 chondromas, 4 fibromas, 45 hamartomas, 15 hamartochondromas, 6 lipomas, 19 angiomas, 5 leiomyomas, 4 schwannomas, 1 neurofibroma, and 21 amyloidomas. Results of laser resection were "very good" in 115 (62%) and "good" in 70 (38%). Complications were minimal: two mediastinal emphysemas, one pneumothorax, and one anesthesia-related cardiac arrest leading to the single death in this series. In general, benign tumors of the proximal endobronchial tree responded well to laser resection when their endoscopic appearance is recognized and prognosis known. Even when recurrent, repeated procedures can be performed easily with good results. This series is probably the largest in the world's literature about endoscopic recognition and the role of laser resection in patients presenting with benign endobronchial tumors.

Adult↗
PubMed1994

Turpentine poisoning: a case report.

The use of turpentine oil for suicidal and homicidal purposes has become quite infrequent with the increased availability of pesticides and toxic substances. Available literature exhibits few case reports of turpentine poisoning. Such a case is reported here which presented as status epilepticus, unresponsive to the usual line of treatment. Detailed clinical examination and inquiry into the case history revealed turpentine poisoning.

Adolescent↗
PubMed1993

Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule.

Synthetic peptides corresponding to microbial epitopes stimulate T cell immunity but their immunogenicity is poor and their half-lives are short. A viral epitope inserted into the complementarity-determining region 3 (CDR3) loop of the heavy chain of a self immunoglobulin (Ig) molecule was generated from the Ig context and was presented by I-Ed class II molecules to virus-specific, CD4+ T cells. Chimeric Ig-peptide was presented 100 to 1000 times more efficiently than free synthetic peptide and was able to prime virus-specific T cells in vivo. These features suggest that antigenized Ig can provide an improved and safe vaccine for the presentation of microbial and other peptides.

Amino Acid Sequence↗
PubMed1993

Microscopic colitis: a diagnosis to consider.

Microscopic colitis is a syndrome of chronic watery diarrhoea for which no cause can be identified other than the presence of diffuse, chronic inflammation in the lamina propria on colonic biopsy. Endoscopically and radiologically the colon appears normal. We studied case records of 215 patients presenting to our institution over a three year period with chronic diarrhoea. Nineteen patients were included in the study where two pathologists agreed on the presence of chronic inflammation on colonic biopsies. All patients had watery diarrhoea with urgency. Stool examination, laboratory indices, radiology of the large and small bowel and colonoscopy were normal in all patients. Patients did not respond to a variety of drugs. A significant improvement was noted in one patient given salazopyrin. In developing countries chronic diarrhoea is most often attributed to infection and treated with antibiotics. Microscopic colitis should be considered in the diagnosis of such patients.

Adult↗
PubMed1993

Outcome of biliary tract surgery in unknown cirrhotics: a case-control study.

The substantial risk of biliary surgery in patients with liver cirrhosis may be reduced by preoperative preparation but the problem of the unknown cirrhotic remains. We studied 18 patients found incidentally to have cirrhosis at surgery. The perioperative complications and the outcome in these patients was compared with 18 non-cirrhotic patients, computer matched for age and sex, undergoing the same operations. Mean blood loss at operation was 324 ml (SD 218.1 ml) in the cirrhotic group and 105 ml (SD 74.7 ml) in the control group (P < 0.01). The postoperative complication rate was 38% in cirrhotics, but zero in controls (P < 0.01). The length of hospital stay was significantly increased in the cirrhotic group (P < 0.01). There was no mortality in either group. The incidental finding of cirrhosis at biliary surgery is associated with increased peroperative bleeding and increased morbidity. There is no increase in mortality in such patients.

Cholecystectomy↗