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Biomedical subjects

K Shah

Publications and source records attributed to K Shah.

At least 37 records · Page 2Linked to original sources

Clinical manifestation of pulmonary embolism.

Results of prospective studies have shown that physicians' estimate of clinical likelihoods of PE have predictive value. The ability of clinicians to assess the factors that determine the probability of disease based on clinical manifestations such as history and signs and symptoms at presentation, and to make bedside estimates of that probability, has not been systematically studied. Data suggest that that this would be a fruitful area of future investigation. Susec et al noted that there has been a total of three studies (including their own) which have examined the clinical features such as risk factors, signs, and symptoms associated with PE in ambulatory outpatients. Hence, the data collected thus far might not be generalizable to the ED patient population. As with other illnesses, the ED patients usually present later and more atypically. The prevalence of PE could be lower among this population compared with hospitalized patients, causing a lower positive predictive value, derivable from the clinical features and risk factors at presentation. Finally, the ED patient population is usually healthier and younger than the hospitalized patients, and it is well recognized that PE can be clinically silent in young patients and that 28% have no associated risk factors. Based on their finding, the authors argue that clinical pathways to risk stratify patients in an ambulatory setting could be less useful than anticipated. The validity of these findings needs further investigation, however.

Adult↗

ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation.

Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) is one of a family of 20 proteins that are involved in transcription and post-transcriptional messenger RNA metabolism. The mechanisms that underlie regulation of hnRNP-K activities remain largely unknown. Here we show that cytoplasmic accumulation of hnRNP-K is phosphorylation-dependent. Mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) efficiently phosphorylates hnRNP-K both in vitro and in vivo at serines 284 and 353. Serum stimulation or constitutive activation of ERK kinase (MEK1) results in phosphorylation and cytoplasmic accumulation of hnRNP-K. Mutation at ERK phosphoacceptor sites in hnRNP-K abolishes the ability to accumulate in the cytoplasm and renders the protein incapable of regulating translation of mRNAs that have a differentiation-control element (DICE) in the 3' untranslated region (UTR). Similarly, treatment with a pharmacological inhibitor of the ERK pathway abolishes cytoplasmic accumulation of hnRNP-K and attenuates inhibition of mRNA translation. Our results establish the role of MAPK/ERK in phosphorylation-dependent cellular localization of hnRNP-K, which is required for its ability to silence mRNA translation.

Arachidonate 15-Lipoxygenase↗

Pharmacological differences between the human and rat vanilloid receptor 1 (VR1).

Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells. Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC(50) values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90+/-0.20 microM; human=1.90+/-0.30 microM: CHO cells: rat=0.20+/-0.06 microM; human=0.19+/-0.08 microM). In CHO cell lines co-expressing either rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the EC(50) values for capsaicin-induced responses were similar in both cell lines (rat=0.35+/-0.06 microM, human=0.53+/-0.03 microM). The threshold for activation by acidic solutions was lower for human VR1 channels than that for rat VR1 (EC(50) pH 5.49+/-0.04 and pH 5.78+/-0.09, respectively). The threshold for heat activation was identical (42 degrees C) for rat and human VR1. PPAHV was an agonist at rat VR1 (EC(50) between 3 and 10 microM) but was virtually inactive at the human VR1 (EC(50)>10 microM). Capsazepine and ruthenium red were both more potent at blocking the capsaicin response of human VR1 than rat VR1. Capsazepine blocked the human but not the rat VR1 response to low pH. Capsazepine was also more effective at inhibiting the noxious heat response of human than of rat VR1.

Amino Acid Sequence↗

Hyaluronic acid skin fillers: adverse reactions and skin testing.

BACKGROUND: Hyaluronic acid (HA) fillers have been proposed as alternatives to other temporary skin fillers, such as bovine collagen, for treating facial skin lines and for providing lip augmentation. Several types of commercial HA fillers are now available in many countries. They include Restylane, which is produced by microbiologic engineering techniques, and Hylaform, which is HA extract derived from rooster combs. They have been approved for use in several countries, but not currently in the United States. There are no recommendations to perform pretreatment skin testing by the manufacturers. OBJECTIVE: Our purpose is to describe and comment on our experiences with Hylaform and Restylane fillers. Observation of any side effects and skin testing results were documented. METHODS: Between September 1996 and September 2000, 709 patients were treated with Hylaform and Restylane and were followed up clinically for at least 1 year. Three of these patients (0.42%) developed delayed skin reactions. Three other patients were referred for evaluation of their skin reactions from other practitioners. Five of these 6 patients agreed to skin testing of their forearms. RESULTS: In the 5 patients tested, challenge intradermal skin testing was positive in 4 patients; the reactions started approximately 8 weeks after injection. CONCLUSIONS: There was a slight incidence of delayed inflammatory skin reactions to two HA fillers. Both of these reactions occurred after the first and repeat injections. Challenge skin testing was positive in 4 of 5 tested patients.

Biocompatible Materials↗

Human papillomavirus-associated cervical cytologic abnormalities among women with or at risk of infection with human immunodeficiency virus.

OBJECTIVE: Correlates of abnormal human immunodeficiency virus cervical cytologic findings were examined among women infected with human immunodeficiency virus and uninfected women. STUDY DESIGN: We performed a cross-sectional analysis of baseline data on demographically similar women with infection or risk factors for it. RESULTS: Among 1050 women without hysterectomy, squamous intraepithelial lesions were more common among women infected with human immunodeficiency virus than among uninfected women (18.8% vs 5.3%; P <.001). In multivariate analysis the association of squamous intraepithelial lesions with human papillomavirus infection was strong; adjusted prevalence ratios were 27 for high-risk, 25 for intermediate-risk, and 10 for low-risk types (95% confidence intervals, 12-58, 12-54, and 4-25, respectively). Much lower adjusted prevalence ratios were seen for the only other factor significantly associated with squamous intraepithelial lesions, namely, infection with human immunodeficiency virus in conjunction with a reduced CD4(+) cell count. Adjusted prevalence ratios were 1.9 for CD4(+) cell counts <200 and 1.6 for CD4(+) cell counts between 200 and 500 (95% confidence intervals, 1.2-3.0 and 1.0-2.5, respectively). Adjusted attributable fractions calculated for this study population indicated that if both human immunodeficiency virus and human papillomavirus were removed, 47.6% of the observed lesions with atypical squamous cells of uncertain significance and 93.4% of the observed squamous intraepithelial lesions would be prevented. CONCLUSION: Squamous intraepithelial lesions are more common among human immunodeficiency virus-infected women and are associated most commonly with high- and intermediate-risk human papillomavirus types and secondarily with human immunodeficiency virus-associated immune compromise.

CD4 Lymphocyte Count↗

PCR-based methylation testing for Prader-Willi or Angelman syndromes using archived fixed-cell suspensions.

All Prader-Willi syndrome (PWS) and 75% of Angelman syndrome (AS) patients have specific DNA methylation pattern alterations that can be used for diagnostic evaluation. The methylation testing identifies a significantly higher proportion of patients as compared to fluorescence in situ hybridization (FISH)-based microdeletion analysis and is thus a useful diagnostic evaluation for clinically suspect, but FISH-negative, patients. We used two independent PCR-based protocols for methylation testing on fixed cell specimens archived after FISH analyses. Changes in DNA methylation due to the procedure of cell fixation were ruled out by testing control specimens before and after fixation. Then methylation testing was carried out on 20 standard fixed-cell supsensions from people suspected for PWS or AS. These fixed specimens were stored after negative FISH analysis for up to 4 years at 4 degrees C in 3:1 methanol/acetic acid. Methylation patterns associated with AS (one specimen) and with PWS (one specimen) were identified for both protocols. The observed methylation patterns were concordant with the phenotypes of the positive individuals and for the two protocols used. We have, thus, shown that archived fixed-cell suspensions from individuals suspected as PWS or AS that were negative for cytogenetic/FISH microdeletions, can now be re-evaluated with PCR-based methylation testing without the need for additional blood samples from the previously studied individuals.

Angelman Syndrome↗

Effect of amoxycillin with or without clavulanate on adenoid bacterial flora.

The effect of antimicrobial therapy with amoxycillin (AMX) or co-amoxiclav (AMC) on the adenoid bacterial flora of 45 children with recurrent otitis media (ROM), scheduled for elective adenoidectomy, was studied. Patients were randomized before surgery into three groups of 15, having had either no antibiotic therapy (control), or 10 days of therapy with AMX or AMC. Core adenoid tissues were quantitatively cultured for aerobic and anaerobic bacteria. Polymicrobial aerobic-anaerobic flora was present in all instances. The predominant aerobes in all groups were alpha-haemolytic and non-haemolytic streptococci, Haemophilus influenzae, Staphylococcus aureus, group A beta-haemolytic streptococci and Moraxella catarrhalis. The prominent anaerobes were Peptostreptococcus spp., Prevotella spp. and Fusobacterium spp. The number of isolates was significantly reduced in those treated with AMX (110; P < 0.05) or AMC (54; P < 0.001) compared with control (148). The number of bacteria per gram of tissue was lower in those treated with both antibiotics. The number of potential pathogens was lower in those treated with AMC compared with the other two groups (P < 0.001 ). The number of beta-lactamase- producing bacteria (BLPB) was lower in those treated with AMC compared with those treated with AMX (P < 0.025) or no antibiotic (P < 0.001). These data illustrate the ability of AMX and AMC to reduce the bacterial load as well as potential pathogens and BLPB from the adenoids of children with ROM.

Adenoids↗

Microbiology of serous otitis media in children: correlation with age and length of effusion.

The purpose of this study was to correlate the microbiology of serous otitis media in children with the duration of the condition and the patient's age. Aspirates of serous ear fluids from 114 children were examined for aerobic and anaerobic bacteria. Bacterial growth was noted in 47 patients (41%). Aerobic organisms only were recovered in 27 aspirates (57% of the culture-positive aspirates); anaerobic bacteria only in 7 (15%); and mixed aerobic and anaerobic bacteria in 13 (28%). A total of 83 bacterial isolates were recovered, accounting for 1.8 isolates per specimen (1.2 aerobes and 0.6 anaerobe). There were a total of 57 aerobic isolates, including Haemophilus influenzae (15 isolates), Streptococcus pneumoniae (13), and Staphylococcus sp (12). Twenty-six anaerobes were recovered, including anaerobic gram-positive cocci (10), Prevotella spp (8), and Propionibacterium acnes (4). The rate of positive cultures (20 of 36; 56%) was higher in patients younger than 2 years of age than in those older than 2 years of age (27 of 78; 35%). Streptococcus pneumoniae and H influenzae were more often isolated in children younger than 2 years of age and those with effusion for 3 to 5 months, whereas anaerobes were recovered more often in those older than 2 years of age and those with effusion for 6 to 13 months. These data illustrate the effects of the length of effusion and age on the recovery of aerobic and anaerobic bacteria in serous otitis media.

Age Factors↗

Bacteriology of adenoids and tonsils in children with recurrent adenotonsillitis.

Adenoids and tonsils electively removed from 25 children with a history of recurrent group A beta-hemolytic streptococci (GABHS) adenotonsillitis were cultured for aerobic and anaerobic bacteria. Two hundred twenty-four organisms (112 aerobes and facultatives, 110 anaerobes, and 2 Candida albicans) were isolated from the tonsils, and 229 (111 aerobes and facultatives and 118 anaerobes) were isolated from the adenoids. Mixed infection was present in all instances, with an average of 9.1 isolates per specimen. The predominant aerobes were Streptococcus sp, Haemophilus influenzae, and GABHS, and the prevalent anaerobes were Peptostreptococcus, Prevotella, and Fusobacterium spp. Beta-lactamase-producing bacteria were detected in 72 isolates recovered from 22 tonsils (88%) and in 74 isolates recovered from 21 adenoids (84%). Discrepancies in the organisms recovered were found between the tonsils and adenoids. Of the aerobic isolates, 20% were isolated only in tonsils and 18% only in adenoids. Of the anaerobes, 20% were found only in tonsils and 26% only in adenoids. This study demonstrates a polymicrobial aerobic-anaerobic flora in both adenoids and tonsils, and discrepancies in recovery of pathogens such as GABHS. The adenoids may serve as a potential source of tonsillitis caused by GABHS.

Adenoids↗

Research in brief: what do medical students know about autism?

Although recent research indicates the importance of early recognition and intervention for children with autism, it is clear that many families remain very dissatisfied with the diagnostic process. In order to improve this situation, it is essential that primary care practitioners, such as GPs, are fully aware of the core symptoms of autism. The present study reports on autism awareness amongst 250 medical students at different stages of their training. Differences between first-year and fourth-year students were compared with respect to their knowledge of various aspects of autism, including diagnosis, cause, symptomatology, treatment and outcome. Fourth-year students were significantly more likely to respond correctly to questions related to diagnostic criteria and core symptoms. However no significant differences were found between first-year and fourth-year students for other aspects, such as possible causes, IQ profiles, prognosis and treatment. These findings suggest that more emphasis needs to be placed on teaching medical students about autism if diagnosis and access to intervention are to be improved.

Adult↗

Key factors in the optimization of paediatric X-ray practice.

Justification of radiological requests, standardization of procedures and optimization of protection measures are key principles in the protection of individuals exposed to ionizing radiation for diagnostic purposes. Nowhere is this more pertinent than in the imaging of children and, following the recent introduction of the Ionising Radiation (Medical Exposure) Regulations, there is now a regulatory requirement for diagnostic radiology departments to demonstrate compliance with these principles. A study was undertaken to compare all aspects of paediatric radiological practice at two specialist and two non-specialist centres. An initial study involved analysis of nearly 3000 patient doses. The second phase of the project involved assessment of referral criteria, radiographic technique and approximately 100 radiographs at each centre by two consultant paediatric radiologists. While all radiographs were found to be diagnostically acceptable, major differences in technique were evident, reflecting the disparity in experience between staff at the specialist and non-specialist centres. The large number of sub-optimum films encountered at the latter suggests that there is a need for specific training of less experienced radiographic and clinical staff.

Child↗

Src-Abl tyrosine kinase chimeras: replacement of the adenine binding pocket of c-Abl with v-Src to swap nucleotide and inhibitor specificities.

Engineered protein kinases with unnatural nucleotide specificity and inhibitor sensitivity have been developed to trace kinase substrate targets. We first engineered unnatural nucleotide specificity into v-Src by mutating one residue, isoleucine 338, to alanine. This position is highly conserved among all kinases in the sense that it is always occupied by either a large hydrophobic residue or threonine. Because of the conservation of this residue and the highly conserved fold of the kinase family, we have attempted to generalize the engineering of all kinases on the basis of our success with v-Src. Although many kinases can be similarly engineered using v-Src as a blueprint, we encountered one kinase, c-Abl, which when mutated, does not display the ability to accept unnatural ATP analogues. To overcome this failure of the engineered c-Abl (T315A) to accept unnatural nucleotides, we developed a new strategy for introducing unnatural nucleotide specificity into kinases. We generated a chimeric kinase in which regions of the kinase domain of c-Abl were swapped with the corresponding regions of v-Src (I338A). Specifically, we engineered two chimeras in which the N-terminal lobe of the SH1 domain of c-Abl was swapped with that of v-Src. These kinase chimeras were found to have the same unnatural nucleotide specificity as that of v-Src (I338A), while retaining the peptide specificity of c-Abl. Thus, these chimeric kinases are suitable for identifying the direct substrates of c-Abl. These engineered chimeric enzymes provide a new strategy for constructing kinases with tailor-made ligand binding properties.

Adenosine Triphosphate↗

Salinity induced behavioural changes in malate dehydrogenase and glutamate dehydrogenase activities in rice seedlings of differing salt tolerance.

The activities of malate dehydrogenase in whole tissue extract (NAD(+)-MDH) as well as in mitochondrial (NAD(+)-MDH) and chloroplastic (NADP(+)-MDH) preparations of aminating (NADH-GDH) and deaminating(NAD(+)-GDH) glutamate dehydrogenases were studied in two sets of rice cultivars differing in salt tolerance grown under moderate (7 dS m(-1)) and high (14 dS m(-1)) NaCl salinity levels. A contrasting response to salinity on enzyme activities was found between the sensitive and tolerant cultivars during a 5-20-day growth period of study. NaCl salinity in situ caused increase in all three MDH activities in salt tolerant cvs. CSR-1 and CSR-3 whereas in salt sensitive cvs. Ratna and Jaya 16-100% inhibition in activities was noted. Chloroplastic MDH was extremely sensitive to NaCl. In seedlings of salt tolerant cultivars concomitant increase in both aminating and deaminating GDH activities was observed with increase in salinity level, whereas in sensitive cultivars under higher salinity level decrease in GDH activity was noted. Under in vitro conditions NaCl concentration in the range 1-1000 mM caused gradual inhibition in MDH activity. With 400 mM NaCl in vitro, complete loss of mitochondrial and chloroplastic MDH activities was observed. GDH activity increased with increasing concentration of NaCl up to 200 mM NaCl and other salts in vitro and was inhibited thereafter. However 800 mM NaCl caused complete loss of deaminating GDH activity from sensitive cultivar but not from tolerant cultivar. Results suggest varying behaviour of MDH and GDH in two sets of rice cultivars differing in salt tolerance and that inhibition in the activities of dehydrogenases in salt sensitive rice cultivars due to salinity may be one of the possible reasons for decreased growth of rice plants under saline conditions.

Journal Article↗

Cervical neoplasia and repeated positivity of human papillomavirus infection in human immunodeficiency virus-seropositive and -seronegative women.

Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4+ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200 cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV-participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN.

Adult↗

Aerobic and anaerobic bacteriology of concurrent chronic otitis media with effusion and chronic sinusitis in children.

OBJECTIVE: To correlate the aerobic and anaerobic microbiologic findings of concurrent chronic otitis media with effusion and chronic maxillary sinusitis. METHODS: Cultures were obtained from 32 children with concurrent chronic otitis media with effusion and maxillary sinusitis who underwent tympanostomy tube placement. RESULTS: A total of 42 isolates, 24 aerobic and 18 anaerobic, were recovered from 30 patients; 27 were isolated from both sites, 4 from the ear only, and 11 from the sinus only. The most common isolates were Haemophilus influenzae (9 isolates), Streptococcus pneumoniae (n = 7), Prevotella species (n = 8), and Peptostreptococcus species (n = 6). Microbiological concordance between the ear and sinus was found in 22 (69%) of culture-positive patients. CONCLUSION: The concordance in recovery of organisms in more than two thirds of the patients illustrates the common bacterial etiology between chronic otitis media with effusion and chronic sinusitis in children.

Bacteria, Aerobic↗

The cost of juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To assess the medical costs and the number of quality-adjusted life years lost owing to juvenile-onset recurrent respiratory papillomatosis (JORRP). DESIGN: We examined hospital and physician charges for JORRP surgical procedures in Maryland in 1994 adjusting for inflation and the cost-charge ratio. Centers for Disease Control and Prevention data on treatment intensity for JORRP were augmented with a review of treatment records for 18 patients with JORRP. Sensitivity analyses were performed. To illustrate the application of our cost estimates, we compare the costs of JORRP to the costs of the surgical procedures that would be necessary to prevent it. RESULTS: We find that the present value at birth of the cost of a single case of JORRP is $201,724 (range, $61,822-$474,334). The annual cost for a single case of JORRP is $57,996 (range, $32,407-$94,114). The annual cost of JORRP in the United States is between $40 million and $123 million depending on the prevalence. Cesarean section (CS) for women with condyloma has been suggested as a potential strategy to prevent JORRP, but its efficacy remains to be determined. Our results suggest that if only 1% of the CSs actually prevented JORRP, this strategy would be a cost-effective means to prevent JORRP. CONCLUSIONS: Studies to reduce the uncertainty surrounding the efficacy of CS and the effect of both CS and JORRP on families need to precede consideration of a policy of CS for women with clinically evident genital condyloma. Patients should be kept thoroughly informed about the role of CS for the prevention of JORRP and the nature of the remaining uncertainties.

Adolescent↗

Radio frequency perforation of cardiac tissue: modelling and experimental results.

Radio frequency (RF) current delivered through a thin catheter can be used to perforate the pulmonary valve or the atrial septum to treat pulmonary atresia in newborns. To understand better the mechanisms of RF perforation, a numerical model is developed, and experiments are performed in isolated canine cardiac tissue. The model consists of a cylindrical domain with a tissue layer between two blood layers. The finite-difference method is used to compute both the potential and temperature distributions. When the tissue temperature exceeds 100 degrees C in all points that are directly in front of the catheter, these points are considered to be instantly vaporised, and the catheter advances over these points. The computed temperature time course coincides with measured temperature at small voltages (< 16 V). Simulated perforation occurs when the voltage exceeds a threshold of 70-80 V for a catheter diameter of 0.30-0.44 mm, which coincides with experimental observations in the myocardium. A voltage exceeding this perforation threshold tends to decrease tissue damage. Shorter electrodes (0.7 mm as against 2.4 mm) with smaller diameters produce a more rapid perforation. In conclusion, numerical simulations provide insights into aspects of RF perforation, such as electrode size, current, speed of perforation and collateral damage.

Animals↗