Liver biopsy under ultrasound control: implications for training in the Calman era.
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Biopsy↗
Biomedical subjects
S Shah
Publications and source records attributed to S Shah.
Deprivation and excess winter mortality.
OBJECTIVE: To investigate the effect of material deprivation on the winter rise in mortality and temperature dependent variations in mortality. DESIGN: Ecological comparison of seasonal mortality at electoral ward level. Main outcome measures were ratios of winter to rest of the year mortality rates (seasonality ratios) and monthly deaths as the outcome variable in a model with monthly average temperature and Townsend score as main predictors. SETTING: Croydon, London, United Kingdom. SUBJECTS: All deaths of Croydon residents for the period 1990-1995. MAIN RESULTS: There was a clear relation between overall mortality and deprivation. There was no evidence of a relation between age and sex standardised seasonality ratios and Townsend scores for all deaths (Kendall's tau = -0.066, p = 0.63) or cardiovascular deaths or respiratory deaths. There was no evidence of an interaction between Townsend score and temperature in the model of ward mortality rates (p = 0.73). These findings were not affected by exclusion of deaths of nursing and residential home residents. CONCLUSION: This study provides no evidence of an effect of deprivation on excess winter mortality or temperature dependent variations in mortality. The findings question simple assumptions about the relation between deprivation and excess winter mortality and highlight the need for further study to guide interventions.
Cold Temperature↗
Complicated diverticulitis of the sigmoid: a prospective study concerning primary resection with secure primary anastomosis.
BACKGROUND: The Hartmann procedure remains the standard concerning the surgical treatment of acute complicated sigmoid diverticulitis. The aim of this study was to prove the possibility of performing a secure primary anastomosis without colostomy in patients with complicated acute diverticulitis. METHODS: From June 1988 to October 1996, 113 patients suffering from acute complicated sigmoid diverticulitis were included in this prospective study. Within 24-48 h of hospital admission, when symptoms of the illness persisted despite the use of antibiotic therapy, the patients underwent primary resection of the sigmoid. In all patients primary anastomosis was performed, using CEEA staplers, avoiding colostomy and intraoperative colon irrigation. RESULTS: During the observation period of 19 days, there was no anastomotic leakage found either by radiological methods or clinical parameters. Two patients died of early septic complications, 1 of therapy-resistant endocarditis. CONCLUSION: The results of this study demonstrate the safety of primary anastomosis after primary resection of the sigmoid under antibiotic conditions, avoiding the disadvantages associated with two-stage procedures.
Acute Disease↗
Issues of consent in colonoscopy: if a patient says 'stop' should we continue?
Colonoscopy is generally performed under intravenous sedation, which may alter a patient's responses and perception. What should be done if, during the procedure, a patient withdraws the consent previously given? The views of gastroenterologists and patients were ascertained by mailing questionnaires to 100 members of the British Society of Gastroenterology and to 100 patients who had undergone colonoscopy with intravenous sedation. Only 1 of 59 eligible consultants who replied said they would stop the procedure after a single request, but a further 51 would stop if repeatedly asked to do so. Of the remaining 7 who would complete the procedure, 1 nevertheless believed that a sedated patient is capable of making a rational decision. Of the 51 patients who returned a usable questionnaire, 25 thought that the procedure should be stopped immediately following a request, while 26 felt that the doctor should continue. The divergent and sometimes inconsistent views found in this study highlighted the need for further clarification of the issue of informed consent for procedures conducted with the patient under sedation.
Anesthesia, Intravenous↗
Evaluation of the factors influencing stomach-specific delivery of antibacterial agents for Helicobacter pylori infection.
Because Helicobacter pylori infection is localized in the gastric mucus layer and at the mucus layer-epithelial cell interface, we have developed amoxycillin- and metronidazole-containing chitosan microspheres for stomach-specific drug delivery. Drug-loaded porous chitosan microspheres were prepared by simultaneous crosslinking and precipitation with sodium tripolyphosphate. The release of antibacterial agents into simulated gastric fluid (SGF, pH 1.2), and the stability and permeability through gastric mucin, were examined at 37 degrees C. Because of the high porosity of drug-loaded chitosan microspheres, all the amoxycillin and metronidazole were released in 2 h. High-performance liquid chromatography assays of the antibacterial agents in SGF at 37 degrees C indicated 40% degradation of amoxycillin after 10 h. Metronidazole was completely stable for up to 24 h in SGF. Amoxycillin and metronidazole were highly permeable through the gastric mucin gel layer. The results of this study show that acid-stable antibacterial agents, such as metronidazole, that rapidly permeate the gastric mucus layer would be very effective for the complete eradication of H. pylori infection when delivered specifically at the site of infection in the stomach.
Amoxicillin↗
Long-term consequences from bladder perforation and/or violation in the presence of transitional cell carcinoma: results of a small series and a review of the literature.
PURPOSE: Perforation of the bladder during transurethral resection is a worrisome complication for most urologists. Little is known about the consequences of seeding of tumor cells into the peritoneum or retroperitoneum. We reviewed several hospital patient databases as well as the literature to determine the outcome of such situations. MATERIALS AND METHODS: We performed a local multi-institutional case and MEDLINE review using key words, such as bladder neoplasm, neoplasm seeding, perforation, rupture, transurethral resection, peritonitis and tumor. We also contacted several urologists and oncologists at major cancer centers in the United States and Europe regarding the incidence and followup of perforated/violated bladder cancer cases. RESULTS: There were 16 bladder violations in the presence of transitional cell carcinoma, including 2 partial cystectomies that had negative margins and no subsequent metastatic recurrences, a bladder tumor that was detected during suprapubic prostatectomy and perforations during transurethral resection (extraperitoneal in 4 cases and intraperitoneal in 9). Two patients died of sepsis and existing metastatic disease, respectively. The only recurrence among the remaining 11 patients developed after intraperitoneal bladder perforation during transurethral resection for Ta grade 2 tumor. Several anecdotal reports discussed local and distal tumor recurrences, suggesting that even superficial transitional cell carcinoma can behave aggressively if grown in an environment outside the bladder. However, these reports are rare. Any benefit of prophylactic chemotherapy was not proved. CONCLUSIONS: While perforation of the bladder during transurethral resection for cancer and the possibility of tumor implantation are matters of concern, our review demonstrates that few patients return with an extravesical tumor recurrence either locally or distally compared to those with a nonruptured bladder after resection. Although our patient sample is small and there are a limited number of reports in the literature, the risk of recurrence still exists and the urologist should be aware of its possibility. Since recurrences are usually rapid, they may easily manifest to the urologist at followup. However, one should also consider chest x-rays and/or computerized tomography to rule out recurrences that are not clinically obvious.
Carcinoma, Transitional Cell↗
Reasoning with uncertainty in pathology: artificial neural networks and logistic regression as tools for prediction of lymph node status in breast cancer patients.
Axillary lymph node status is an important prognostic feature for patients with breast cancer, but the therapeutic value of axillary lymphadenectomy is controversial. It would be useful to be able to predict the status of axillary lymph nodes before lymphadenectomy from prognostic features evaluated in a previous breast biopsy. This prediction would be useful to optimize the treatment of patients with breast cancer who are unlikely to have nodal metastases. We studied 279 patients with invasive breast carcinoma treated with modified radical mastectomy or with lumpectomy combined with axillary lymph node dissection. Prognostic factors evaluated were age, histologic type of invasive tumor, presence of associated ductal and/or lobular carcinoma in situ, lesion size, histologic and nuclear grades, DNA index, presence of multiploidy by flow cytometric analysis, and immunocytochemical expression of estrogen and progesterone receptors, proliferating nuclear cell antigen, and HER-2/neu oncogene. Several probabilistic neural networks (NNs) with genetic algorithms were developed using prognostic features as input neurons and lymph node status (positive or negative) as output neurons. The data were also studied with multiple regression and logistic regression analysis. The best NN model trained with 224 cases using 19 input neurons. It classified correctly 49 (89.0%) of 55 unknown cases (specificity, 97.2%; sensitivity, 80.0%; positive predictive value, 93.8%; negative predictive value, 87.5%). Several statistically significant models could be fitted with both multiple regression and logistic regression. The logistic regression model fitted with 240 cases using 6 independent variables estimated correctly 26 (66%) of 39 holdout cases. NNs and logistic regression models offer potentially useful tools to estimate the status of axillary lymph nodes of breast cancer patients before axillary lymphadenectomy. Future prospective studies with larger groups of patients and perhaps better prognostic markers are needed before these predictive multivariate models become ready for clinical use.
Adult↗
Serum leptin concentrations in hyperinsulinemia in the sets of obese, lipodystrophic and/or non-obese patients.
OBJECTIVE: To study the relationship between serum leptin and circulating insulin under basal and in response to oral glucose administration in hyperinsulinemic patients with or without obesity. MATERIAL AND METHOD: Fifteen female patients of known hyperinsulinemia provided material for the study. Leptin and insulin in sera were estimated by radioimmunoassay methods. RESULTS: Eight of the 15 hyperinsulinemic patients with high body mass index (BMI) (31 +/- 0.94 kg/m2) had significantly (p < 0.01) elevated serum leptin concentrations (26.1 +/- 2 ng/ml) as compared to the levels in the remaining seven non-obese hyperinsulinemic patients with BMI of 20 +/- 1.0 kg/m2; their mean levels of serum leptin were low 5.7 +/- 1.1 ng/ml. Four of the latter group had face-sparing partial lipodystrophy. The mean circulating leptin concentrations in the control group of seven healthy normoinsulinemic and regularly menstruating women with normal BMI (19 +/- 0.95 kg/m2) were 13.7 +/- 1.8 ng/ml. DISCUSSION: The results of the present study in 15 hyperinsulinemic patients show that circulating levels of leptin are not related to serum insulin. However, there was a positive correlation with BMI. An interesting observation of the study is that, notwithstanding the normal BMI, the group of hyperinsulinemic patients with face-sparing partial lipodystrophy had the lowest levels of circulating leptin concentrations. They were closer to the values found in prepubertal girls.
Adolescent↗
Genetic linkage analysis of multicase families with fibromyalgia syndrome.
OBJECTIVE: Based on the reports of familial aggregation of fibromyalgia (FM) syndrome, we investigated its possible genetic linkage to HLA by studying multicase families. METHODS: Forty Caucasian multicase families with a diagnosis of FM (American College of Rheumatology criteria) in 2 or more first degree relatives were investigated. Eighty-five affected and 21 unaffected members of 41 sibships were studied. Depression symptomology was assessed by Zung Self-rating Depression Scale (SDS). HLA typing was performed for A, B, and DRB 1 alleles, and haplotypes were determined with no knowledge of the subject's diagnosis. We investigated genetic linkage to the HLA region by evaluating sibships in multicase families. RESULTS: Sibship analysis showed significant genetic linkage of FM to the HLA region (p = 0.028). Subgroup analysis was also performed for 17 families where the proband was also noted to have depression (with an SDS index value > or =60). We found that the presence of depression did not influence the observed results (p = 0.22). CONCLUSION: . Our study of 40 multicase families confirms existence of a possible gene for FM that is linked with the HLA region. Our results should be regarded as preliminary and their independent confirmation by other studies is warranted.
Adult↗
The effects of antisense to Gialpha2 on opioid agonist potency and Gialpha2 protein and mRNA abundance in the mouse.
In this study, mice received a single intracerebroventricular (i.c.v. ) injection of an antisense oligodeoxynucleotide (ODN) directed towards the mRNA of Gialpha2. Controls received a saline or a nonsense ODN injection. The subsequent effects on protein levels and mRNA of Gialpha2 were determined in mouse striatum, as well as, the effect on opioid ([d-Ala2, d-Leu5]-enkephalin; DADLE) inhibition of cyclic AMP (cAMP) formation in striatum and morphine analgesic potency. At 48 h after treatment, maximal inhibition (Emax) of cAMP formation was significantly reduced for the antisense group compared to controls. Antisense ODN treatment only changed the Emax and did not significantly alter the IC50s of the dose-effect curves for inhibition of cAMP formation. Antisense ODN, but not nonsense ODN, significantly reduced morphine's analgesic potency by >2-fold, 48 h following treatment. Using a quantitative immunoblotting procedure, antisense treatment was shown to decrease striatal Gialpha2 protein 48 h after antisense injection, while there were no changes in protein levels at 2, 12 and 24 h. In contrast, no changes in Gialpha2 mRNA in mouse striatum were noted at any time after antisense treatment. Taken together, these data suggest that Gialpha2 mediates opioid-induced analgesia and opioid inhibition of cAMP production in the mouse. These data also suggest that antisense reduces target protein by a mechanism independent of changes in mRNA abundance.
Analgesics, Opioid↗
Long-term remission of AIDS-related primary central nervous system lymphoma associated with highly active antiretroviral therapy.
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Acquired Immunodeficiency Syndrome↗
T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells.
The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling and induction of T cell-specific interferon (IFN)-gamma expression in the development of T helper cell (Th)1-type pathology were examined in two different models of experimental colitis. In each model, abnormal reconstitution of the T cell compartment in immunodeficient mice by adoptive cell transfer leads to a wasting syndrome and inflammation of the colon, induced by IFN-gamma and tumor necrosis factor (TNF)-alpha-producing T cells. We show here that treatment with anti-IL-12 antibodies in one of the models, or reconstitution with T cells from Stat-4-deficient (Stat-4(null)) mice in both models resulted in a milder disease in the majority of recipient animals, compared with those that were left untreated or that had been reconstituted with wt cells. Protected mice in each group also harbored lower frequencies of IFN-gamma-producing T cells than did diseased mice, suggesting that effects on wasting and colitis resulted from the attenuation of IFN-gamma expression by T cells. To test whether the development of pathogenic T cells in the two colitis models was directly dependent on T cell-specific IFN-gamma expression, IFN-gammanull donors were used for T cell reconstitution in each system. Surprisingly, large numbers of IFN-gammanull-reconstituted mice developed wasting and colitis, which in many cases was of comparable severity to that seen in animals reconstituted with wt cells. Furthermore, T cells from these animals expressed TNF-alpha, demonstrating that they had retained the ability to produce another proinflammatory cytokine. Taken together, these results demonstrate that in some forms of chronic experimental colitis the development of pathogenic T cells is influenced predominantly, though not exclusively, by IL-12 via the actions of Stat-4 proteins. Furthermore, our data suggest that in the models of colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways are not limited to the induction of IFN-gamma gene expression in T lymphocytes.
Animals↗
Major binding sites for the nuclear import receptor are the internal nucleoporin Nup153 and the adjacent nuclear filament protein Tpr.
A major question in nuclear import concerns the identity of the nucleoporin(s) that interact with the nuclear localization sequences (NLS) receptor and its cargo as they traverse the nuclear pore. Ligand blotting and solution binding studies of isolated proteins have attempted to gain clues to the identities of these nucleoporins, but the studies have from necessity probed binding events far from an in vivo context. Here we have asked what binding events occur in the more physiological context of a Xenopus egg extract, which contains nuclear pore subcomplexes in an assembly competent state. We have then assessed our conclusions in the context of assembled nuclear pores themselves. We have used immunoprecipitation to identify physiologically relevant complexes of nucleoporins and importin subunits. In parallel, we have demonstrated that it is possible to obtain immunofluorescence localization of nucleoporins to subregions of the nuclear pore and its associated structures. By immunoprecipitation, we find the nucleoporin Nup153 and the pore-associated filament protein Tpr, previously shown to reside at distinct sites on the intranuclear side of assembled pores, are each in stable subcomplexes with importin alpha and beta in Xenopus egg extracts. Importin subunits are not in stable complexes with nucleoporins Nup62, Nup93, Nup98, or Nup214/CAN, either in egg extracts or in extracts of assembled nuclear pores. In characterizing the Nup153 complex, we find that Nup153 can bind to a complete import complex containing importin alpha, beta, and an NLS substrate, consistent with an involvement of this nucleoporin in a terminal step of nuclear import. Importin beta binds directly to Nup153 and in vitro can do so at multiple sites in the Nup153 FXFG repeat region. Tpr, which has no FXFG repeats, binds to importin beta and to importin alpha/beta heterodimers, but only to those that do not carry an NLS substrate. That the complex of Tpr with importin beta is fundamentally different from that of Nup153 is additionally demonstrated by the finding that recombinant beta or beta45-462 fragment freely exchanges with the endogenous importin beta/Nup153 complex, but cannot displace endogenous importin beta from a Tpr complex. However, the GTP analogue GMP-PNP is able to disassemble both Nup153- and Tpr-importin beta complexes. Importantly, analysis of extracts of isolated nuclei indicates that Nup153- and Tpr-importin beta complexes exist in assembled nuclear pores. Thus, Nup153 and Tpr are major physiological binding sites for importin beta. Models for the roles of these interactions are discussed.
Amino Acid Sequence↗
NHS performance tables for breast screening.
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Breast Neoplasms↗
Intra-articular tophus presenting as a loose body.
In chronic tophaceous gout, tophi may occur in various tissues of the body. The joints are one of the main tissues of the tophaceous deposits. The articular surface may be coated by heavy deposits. We present a case of a patient with chronic tophaceous gout where the tophaceous deposits formed an intra-articular mass causing symptoms of a loose body.
Gout↗
Single or triple dose piperacillin prophylaxis in elective cesarean section.
OBJECTIVE: To evaluate the efficacy and safety of piperacillin in the prevention of perioperative febrile morbidity in elective cesarean sections, a combination of cephradine plus metronidazole vs. a control group which did not receive any antibiotic prophylaxis. METHOD: 198 women undergoing elective cesarean section were included in a randomized control study to compare the prophylactic efficacy and safety of a single dose (4 g) or three doses (2 g) of piperacillin, three doses of cephradine plus metronidazole combination, when administered peri-operatively and a control group which did not receive prophylactic antibiotics. RESULT: 198 women were randomized to the study, but 14 had to be excluded leaving 184 for analysis. Statistically significant difference was reached when comparing the piperacillin groups (group A and group C) with control (group D) in the prevention of postoperative febrile morbidity inclusive of wound infection and endomyometritis (single-dose piperacillin group A: Relative Risk = 0.14, 95% CI 0.03-0.58). Multi-dose piperacillin therapy group C: R.R. = 0.27, 95% CI 0.10-0.77). The combination of cephradine and metronidazole (group B) when compared with the control group did not show any statistical significant difference in prevention of postoperative febrile morbidity (R.R.= 0.49, 95% CI 0.22-1.10). Single-dose piperacillin when compared to multi-dose piperacillin regimen appears to be more effective at reducing postoperative infective morbidity but this is not statistically significant (R.R. = 0.51, 95% CI 0.10-2.65). When febrile morbidity is separated into wound infection and myometritis, the reduction rates in either of them in each antibiotic study group A, B and C compared to the control group D are not significant except when study groups A and C are combined and compared to control group D (R.R. = 0.21, 95% CI 0.76-0.06). CONCLUSION: Piperacillin single agent therapy, either as a single dose of 4 g or a triple dose of 2 g, is effective and safe in the prevention of postoperative infection when given as prophylaxis in elective cesarean cases.
Anti-Infective Agents↗
ST segment elevation and the prediction of hospital life-threatening complications: the role of right ventricular and posterior leads.
UNLABELLED: Accurate prognosis in suspected acute myocardial infarction (AMI) is essential for appropriate use of thrombolytic therapy and primary angioplasty. However, previous models may be limited because the 12-lead electrocardiogram (ECG) does not examine the right ventricular (RV) and posterior myocardium. We evaluated ST segment elevation (STSE) in posterior (V7-V9) and RV (V4R-V6R) leads to determine their predictive value for hospital life-threatening complications (HLTCs). METHOD AND RESULTS: This prospective trial of seven Midwestern hospital emergency departments (EDs) had inclusion criteria of age 35 years, chest pain suggestive of ischemia, and coronary care unit (CCU) admission. ECG leads were test positive if STSE was > 0.1 mV. Patients were positive for HLTCs if ED or inpatient hospital course included: ventricular fibrillation or tachycardia, second- or third-degree block, shock, arrest, or death. Univariate and multivariate analyses were performed to test each lead's association with HLTCs. Of 533 patients, 64.7% (345/533) had AMI and 15.8% (85/533) had HLTCs. The sensitivity of 18 leads for HLTCS was increased by 5.8%, but specificity decreased by 8.2%. ECG subgroups by STSE were associated with the following HLTC rates: inferior/+RV (32.4%); anterior (29.5%), lateral (23.1%), inferior RV (17.9%), and posterior (16.2%). V1 (odds = 3.2) and V6R (odds = 3.1) were statistically significant independent predictors. CONCLUSION: Posterior and RV leads did not increase the ECG's overall prognostic value, but in the presence of inferior STSE, were associated with low and high complication rates, respectively. Right and left precordial leads were the best predictors of HTLCs.
Adult↗