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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 199 records · Page 11Linked to original sources

Acute ethanol exposure decreases the analgesic potency of morphine in mice.

Chronic (7 days), forced ethanol drinking can decrease the analgesic potency of opioid agonists in mice. In the present study, the effect of short-term ethanol treatment was examined using forced ethanol access and ethanol injection protocols. Mice were given forced access to 1, 3 or 7% (v/v) ethanol for 24 hr and then tested for s.c. morphine analgesia using the tailflick assay. Controls had access to water. Another group of mice was injected i.p. with 2.5 g/kg ethanol or water 4 times over a 21 hr period and tested 3 hr after the final injection for morphine analgesia. Other mice were injected once i.p. with 1, 2 or 3 g/kg ethanol or water and tested 24 hr later using the tailflick. In the forced access study, ethanol dose-dependently decreased morphine's analgesic potency with the highest dose (7%) producing a 1.6-fold shift in the ED50. This decrease in morphine potency was similar to that found in a related study using 7% ethanol for 7 days (1.8-fold shift). Repeated ethanol injections significantly reduced the analgesic potency of morphine (1.9-fold shift), whereas, a single injection of 1, 2 or 3 g/kg ethanol did not alter the potency of morphine. Control studies indicated that neither 24 hr water nor food deprivation affected morphine potency. Overall, these data show that sustained exposure to ethanol over a 24 hr period will dose-dependently decrease morphine's analgesic potency.

Analgesics, Opioid↗

Latex allergy and latex sensitization in children and adolescents with meningomyelocele.

BACKGROUND: The high prevalence of clinical latex allergy and latex sensitization in children with meningomyelocele has been widely reported. It has also been noted that these same children have a higher than expected prevalence of atopic disease. It would be useful to have a safe, sensitive, and specific skin test to detect latex sensitivity and to know how well this test compares with available in vitro tests. It would likewise be helpful to know as fully as possible the characteristics of the individual and to evaluate the relative importance of factors suspected to contribute to clinical latex allergy and latex sensitization in this population. METHODS: A group of 116 children and adolescents 1 to 20 years of age were recruited for the study. An extensive history of latex allergy, atopic diseases, and surgical procedures was taken on all subjects. Each subject had either a latex skin test or an in vitro study for latex-specific IgE, and 67 subjects had both tests simultaneously. Eighty-five subjects had epicutaneous skin tests to a panel of environmental allergens. RESULTS: Overall, 25 of 116 (21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%) were sensitized to latex. The sensitivity and specificity of skin tests for clinical latex allergy were slightly greater than for the in vitro test (100% vs 95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and negative predictive value of skin testing for clinical latex allergy were also greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a significant variable for both latex allergy and latex sensitization. The number of surgical procedures undergone and the presence of positive skin test responses to environmental allergens were significantly correlated with latex sensitization but not with clinical allergy to latex. CONCLUSIONS: A sensitive, specific, and safe skin test for latex sensitivity appears superior to in vitro testing for latex allergy. Age, number of surgical procedures, and the presence of positive allergen skin test responses are significantly correlated with latex sensitization. Age alone is significantly correlated with clinical allergy to latex.

Adolescent↗

Predictability of spherical photorefractive keratectomy for myopia.

OBJECTIVE: This study aimed to examine the effects of purely spherical excimer laser photorefractive keratectomy (PRK) for myopia. DESIGN: Consecutive case series. PARTICIPANTS: A total of 3218 eyes with a mean preoperative mean spherical equivalent (MSE) of -3.75 diopters (D) +/- 1.73 D standard deviation (SD) (range, -1.00 D to -11.88 D) underwent PRK with a Nidek EC-5000 excimer laser. Eyes were divided into groups based on the degree of preoperative myopia in 1 D steps. INTERVENTION: All eyes underwent PRK with a Nidek EC-5000 excimer laser. MAIN OUTCOME MEASURE: Visual and refractive outcome of PRK treatment was measured. RESULTS: After a mean follow-up period of 52.6 weeks (range, 26-150 weeks), the final MSE was -0.07 D (+/-0.68 D) (range, -5.50 D to +4.50 D). Of the 3218 eyes, 2919 (90.7%) were within 1.00 D of emmetropia, and 3038 (94.4%) of eyes had an uncorrected visual acuity of 20/40 or better, with 1886 (58.6%) achieving 20/20 or better visual acuity. Eyes in the lower preoperative myopia groups had a greater chance of attaining 20/40 unaided visual acuity than those in the higher groups (e.g., 98.3% of the -2D group and 53.6% of the -9D group achieved 20/40 unaided visual acuity). Overall, mean postoperative haze was 0.29+/-0.39 SD (scale, 0-3), and 29 eyes (0.9%) lost 0.3 or more logarithm of the minimum angle of resolution (LogMAR) unit of best-corrected visual acuity. CONCLUSIONS: Excimer laser PRK is an effective treatment for myopia of up to -9.00 D. The outcome parameters are less predictable for eyes with greater than -9.00 D of myopia.

Adult↗

Modulation of sensory nerve function in the airways.

Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms thought to account for the bronchoconstriction induced by these agents is via reflex activation of the cholinergic pathway. An increase in sensory nerve (afferent) activity in asthma might account for the increased responsiveness to these agents. If so, a number of strategies are available to inhibit the function of afferent nerves which could lead to a suppression of bronchial hyperresponsiveness, including (1) inhibition of afferent activity, (2) inhibition of neuropeptide release and (3) antagonism of tachykinin receptors. As there are numerous reviews dealing with the latter, in this review Domenico Spina, Saloni Shah and Selena Harrison focus on the first two strategies.

Anti-Asthmatic Agents↗

Epithelial debridement for secondary hyperopia following myopic excimer laser photorefractive keratectomy.

BACKGROUND: To evaluate epithelial debridement for the treatment of persistent hyperopia in eyes that had photorefractive keratectomy (PRK). SETTING: Optimax Laser Eye Clinics, Manchester, London, Bristol, England. METHODS: Epithelial debridement was performed on 46 eyes to reduce the hypermetropia following excimer laser PRK. RESULTS: Mean age of the patients was 43 years +/- 9.7 (SD). Mean refractive change was -0.51 diopter (D) +/- 0.76 (range +0.75 to -2.50 D). Mean change in best corrected visual acuity (BCVA) was 0.00 Logmar units (range +0.40 to -0.20 units), although 33% of eyes lost one line or more of Logmar BCVA. Mean follow-up after debridement was 61.0 +/- 26.9 weeks (range 26 to 140 weeks). CONCLUSIONS: Epithelial debridement is an unpredictable procedure to treat secondary hyperopia after PRK, producing a small mean change in spherical equivalent with a wide range of results. A significant number of eyes lost one line or more of Logmar BCVA. We therefore do not advocate epithelial debridement after PRK.

Adult↗

The ethnic minority traveler.

Although the ethnic minority traveler is exposed to the same risks as other travelers, there are special considerations that make them vulnerable to certain diseases. In addition, many ethnic minority travelers are traditionally underserved by the medical community and often travel without the benefit of adequate counseling and immunization. The specific disease entities covered in this article include parasitic diseases (e.g. malaria, trypanosomiasis, intestinal helminths), tuberculosis, and other respiratory diseases, dengue, and sexually transmitted diseases and HIV.

Blood Transfusion↗

Comparative anti-anaerobic activity of Men 10700, a penem antibiotic.

The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third generation cephalosporins against 120 strains of anaerobes. The organisms tested comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis and speciated members of the genera Fusobacterium, Veillonella and Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and was more potent than metronidazole against all species except C. difficile and P. anaerobius. The spectrum of activity of Men 10700 suggests this agent may be useful for treating infections caused by anaerobes.

Amoxicillin-Potassium Clavulanate Combination↗

Peer-led asthma education for adolescents: impact evaluation.

PURPOSE: To examine the impact of a peer-led asthma education program on asthma knowledge, attitudes, and quality of life among adolescents. METHODS: A controlled trial was conducted in two girls' high schools situated in an area of high unemployment and low socioeconomic status, and with a large non-English-speaking community. One school received the intervention and the second school acted as a comparison school. The Triple A (Adolescent Asthma Action) program was implemented in the intervention school and involved Year 11 student peer leaders instructing Year 10 students about asthma. The Year 10 students then developed asthma-related health messages into student asthma performances which were presented to the main student body. Outcomes were evaluated by questionnaire. RESULTS: The Triple A program led to a significant improvement in asthma knowledge in both students with asthma and their peers. This effect occurred not only in students conducting the asthma performances (Year 10), but also in students in the audience (Year 7). Students held favorable attitudes toward asthma, with high degrees of tolerance and moderate internal locus of control. Asthma-related quality of life was not altered by the intervention. CONCLUSION: Peer-led asthma education was well received in the high school setting and led to important improvements in asthma knowledge among students with asthma and their peers.

Adolescent↗

Inflammatory breast carcinoma: a community hospital experience.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare form of rapidly progressive breast cancer. We reviewed the diagnosis, treatment, and outcome of IBC in our inner city community-based hospital and compared results with previous published reports. STUDY DESIGN: Twenty-five patients were diagnosed and treated for IBC at the Catholic Medical Center of Brooklyn and Queens during the 6-year period of January 1989 through December 1995. Criteria for inclusion in this study were clinical or histopathologic evidence, or both, of inflammatory carcinoma. RESULTS: IBC comprised 2.0% (25 of 1,257) of all breast cancer patients initially diagnosed during this study. All presented with clinical signs of IBC. Invasion of dermal lymphatics by neoplastic cells was demonstrated in 68% (17 of 25) of biopsy specimens. Sixty-eight percent (17 of 25) of patients presented with metastatic (ie, stage IV) disease and 28% (7 of 25) with stage IIIb; one patient (4%) died before staging. Estrogen and progesterone receptor studies were done on 72% (18 of 25) of all specimens. Of those patients who died, 85% were estrogen and progesterone receptor negative; of those surviving, 60% were estrogen receptor positive. Twenty (80%) of the 25 patients died, after a mean survival of 11.8 months and 5 (20%) remain alive, with a mean survival of 44.8 months. Of those who died, 85% were stage IV at presentation. All five survivors were stage IIIb at presentation. Patients underwent a variety of multimodal therapies. Survival was significantly associated with earlier stage at diagnosis and estrogen receptor positivity. CONCLUSIONS: IBC is characterized by rapid progression and dismal outcome. Earlier stage at diagnosis and positive estrogen receptor status suggest a more favorable prognosis. Neoadjuvant chemotherapy, as part of a multimodal approach, has significantly improved the outcome for IBC, but this is limited to patients with stage IIIb disease. Most of our patients presented with stage IV disease. If improvement is to be realized at the community level, limited health care resources must be directed toward aggressive physician and public education.

Adenocarcinoma↗

CD30 is a CD40-inducible molecule that negatively regulates CD40-mediated immunoglobulin class switching in non-antigen-selected human B cells.

We used our monoclonal model of germinal center maturation, CL-01 B cells, to investigate the role of CD30 in human B cell differentiation. CL-01 cells are IgM+ IgD+ CD30+ and switch to IgG, IgA, and IgE when exposed to CD40L and IL-4. Switching is hampered by CD30 coengagement, possibly through interference with the CD40-mediated NF-kappaB-dependent transcriptional activation of downstream C(H) genes. The physiological relevance of this phenomenon is emphasized by similar CD30-mediated effects in naive B cells. Expression of CD30 by these cells is induced by CD40L but is inhibited by B cell receptor coengagement and/or exposure to IL-6 and IL-12. Our data suggest that CD30 critically regulates the CD40-mediated differentiation of non-antigen-selected human B cells.

Antibodies, Monoclonal↗

p21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo.

The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression. In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer.

Animals↗

Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway.

1. Electrical field stimulation (EFS) of guinea-pig isolated main bronchi induced a non-adrenergic non-cholinergic (NANC) contractile response. Nociceptin (0.01-1 microm) significantly inhibited the contractile response to EFS (P<0.01), but not to capsaicin (P>0.05). 2. The mu-, delta- and kappa-opioid receptor antagonists, naloxone (0.3 microM), naltrindole (3 microM) and norbinaltorphimine (1 microm), respectively, did not significantly affect the inhibitory effect of nociceptin (0.03 microM; P>0.05). 3. The novel nociceptin antagonist, [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (0.03-1 microM); the sigma ligands, carbetapentane (30 microM), 3-phenylpiperidine (30-100 microM) and (+)-cyclazocine (10-100 microM) significantly reversed the inhibitory effect of nociceptin (0.03 microM, P<0.05). In contrast, rimcazole, did not significantly reverse the inhibitory effect of nociceptin (0.03 microM) at any concentration tested (P>0.05). 4. EFS of guinea-pig bronchial preparations significantly increased SP-LI release above basal SP-LI (P<0.05). In the presence of nociceptin (1 microM), EFS induced a significant increase in SP-LI release above basal SP-LI release (P<0.05). Nociceptin caused a 59+11% (n=5) inhibition of EFS-induced release of SP-LI. 5. Nociceptin reduces the release of sensory neuropeptides induced by EFS, but not capsaicin, from guinea-pig airways. These experiments provide further evidence for a role for nociceptin in regulating the release of sensory neuropeptides in response to EFS.

Animals↗

Trisomy 13 and myeloid malignancy--characteristic blast cell morphology: a United Kingdom Cancer Cytogenetics Group survey.

We retrospectively report data on 28 patients with haematological malignancy and trisomy 13 (25 cases) or tetrasomy 13 (three cases) as the primary acquired cytogenetic change. Peripheral blood and/or bone marrow morphology was reviewed in 25/28 cases and the final diagnosis was as follows: AML M0 (11), AML M1 (6), AML M2 (2), AML M4 (2), AML M5b (1), AML M6 (1), RAEB-t (3), RAEB (1), RA (1). All three cases with tetrasomy 13 had AML M0. Characteristic small hand-mirror blasts with cytoplasmic blebs and tails and scanty small granules were seen in 13/25 cases and 18/25 cases had small blasts which could easily be mistaken for lymphoblasts. Trilineage dysplasia was present in 8/28 cases. Median patient survival was 3 months. We conclude that trisomy 13 is particularly associated with acute myeloid leukaemia with minimal differentiation (AML MO), often has distinctive morphological features, and has a poor prognosis.

Acute Disease↗

Vancomycin susceptibility as an aid to the identification of lactobacilli.

Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two clinical isolates, have been identified by API 50 CHL and tested for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other antibiotics was not species-specific. Differential susceptibility to vancomycin may be helpful in speciation of lactobacilli.

Anti-Bacterial Agents↗

Impact of RNase L overexpression on viral and cellular growth and death.

The biologic actions of interferons (IFNs) are complex and involve multiple biochemical mechanisms, including the 2-5A system, a regulated RNA decay pathway. The 2-5A system is implicated in the antipicornavirus activity of IFN and in the control of apoptosis. To further investigate involvement of the 2-5A system in the control of viral and cellular growth and death, human RNase L cDNA was stably expressed in murine 3T3 cells from a constitutive cytomegalovirus (CMV) promoter. A clonal cell line, 3T3/pLZ, was isolated that overexpressed RNase L by >100-fold compared with levels of the endogenous murine RNase L. Interestingly, human RNase L levels in 3T3/pLZ cells decreased 3-fold as cells entered a confluent, growth arrest state, suggesting autoregulation. Overexpression of human RNase L greatly enhanced both the cell growth inhibitory activity of IFN and the proapoptotic activity of staurosporine. Furthermore, high levels of RNase L suppressed the replication of diverse viruses: encephalomyocarditis virus, vesicular stomatitis virus, human parainfluenza virus-3, and vaccinia virus. Additional reductions in viral growth were obtained by treating 3T3/pLZ cells with IFN (a + beta) before infections. These results directly demonstrate the anticellular and antiviral potential of the 2-5A system.

3T3 Cells↗

Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status.

The in-vitro activity of the novel ketolide HMR 3647 was compared with four other macrolides against 335 strains of staphylococci, pneumococci and enterococci with predetermined susceptibility status to erythromycin. HMR 3647 was the most active agent against staphylococci (irrespective of methicillin resistance) of sensitive (MIC90 = 0.25 mg/L) or inducibly resistant phenotype (MIC90 = 2 mg/L), but was inactive against constitutively resistant strains. HMR 3647 was very active against erythromycin-sensitive enterococci (MIC90 = 0.06 mg/L), irrespective of vancomycin resistance, but less active against strains that were resistant to erythromycin (MIC90 = 32 mg/L). The ketolide was highly active against pneumococci (irrespective of penicillin resistance), both erythromycin sensitive (MIC90 = 0.03 mg/L) and erythromycin resistant (MIC90 = 0.25 mg/L). A bactericidal action was found against some erythromycin-sensitive staphylococci, pneumococci and Enterococcus faecium. The microbiological properties of HMR 3647 are thus superior to those of other macrolides.

Anti-Bacterial Agents↗

The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis, and beta-lactamase production in Staphylococcus aureus.

Extracts of tea (Camellia sinensis) can reverse methicillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) and also, to some extent, penicillin resistance in beta-lactamase-producing S. aureus. These phenomena are explained by prevention of PBP2' synthesis and inhibition of secretion of beta-lactamase, respectively. Synergy between beta-lactams and tea extracts were demonstrated by disc diffusion, chequerboard titration and growth curves. Partition chromatography of an extract of green tea on Sephadex LH-20 yielded several fractions, one of which contained a virtually pure compound that showed the above-mentioned activities, at concentrations above about 2 mg/L. The observed activities are novel and distinct from the previously reported direct antibacterial activity of tea extracts. Prevention of PBP2' synthesis offers an interesting possible new approach for the treatment of infections caused by MRSA.

Bacterial Proteins↗