Emerging trends in the management of the impalpable testis.
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Anesthesia↗
Biomedical subjects
S Ahmed
Publications and source records attributed to S Ahmed.
Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B.
We have analyzed the molecular dynamics of emergence of drug-resistant strains in patients receiving lamivudine therapy for chronic hepatitis B. Twenty consecutive patients with lamivudine resistance were studied (13 hepatitis B e antigen [HBeAg]-positive patients and 7 HBe antibody [anti-HBe]-positive patients). Determination of viral genotype, precore mutants, and polymerase gene mutants (L528M, M552V, M552I) was performed using the research version of Lipa-HBV. Quantitative analysis of HBV DNA was performed using both branched DNA (bDNA) and polymerase chain reaction (PCR) assays. Polymerase mutants (genotypic resistance) were found in 16 of 20 patients. Genotypic resistance was detected earlier than the phenotypic resistance (P =.004). Quantitative PCR allowed detection of viral DNA throughout the entire study period in 16 of 20 patients. Analysis of pretreatment variables showed that high alanine transaminase (ALT) levels (>3 x the upper limit of normal [ULN]) was associated with a more rapid selection of drug-resistant mutants (P =.027) and a high hepatitis B virus (HBV) DNA level (>1,497 Meq/mL, bDNA) with a more rapid occurrence of phenotypic resistance (P =.04). At the time of viral breakthrough, the mean serum HBV-DNA values were not different from the pretreatment values (P =.37). ALT levels were higher in anti-HBe-positive patients compared with pretreatment values and to HBeAg-positive patients (P =.01). In 8 patients, antiviral therapy was modified after viral breakthrough, with the introduction of famciclovir and/or interferon alfa. Viral DNA became undetectable by bDNA in 3 patients who received interferon. Our results suggest that genotypic assays for polymerase mutant detection and quantitative determination of viremia with highly sensitive assay are warranted for an optimal monitoring of antiviral therapy of chronic hepatitis B.
2-Aminopurine↗
Post-traumatic amnesia after closed head injury: a review of the literature and some suggestions for further research.
Post-traumatic amnesia (PTA) is a transient sequela of closed head injury (CHI). The term PTA has been in clinical use for over half a century, and generally refers to the subacute phase of recovery immediately after unconsciousness following CHI. The duration of PTA predicts functional outcome after CHI, but its pathophysiological mechanism is not known. This paper compares current methods of determining the duration of PTA, summarizes reports on neuropsychological deficits in PTA, reviews available data that allow inferences about its mechanism, and suggests methods for further exploration of its pathophysiology.
Amnesia↗
Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE) in the treatment of advanced pancreatic carcinoma: a phase II study.
Encouraging results using cisplatin, cytarabine, and caffeine for the treatment of pancreatic carcinoma prompted a phase II study using these agents and adding continuous intravenous infusion (CI) 5-fluorouracil (5-FU) (PACE). Patients with advanced pancreatic adenocarcinoma who had not received prior cytotoxic therapy were eligible. Treatment consisted of the following: on day 1, the administration of cisplatin 100 mg/m2 IV, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and on days 3 to 21, 5-FU 250 mg/m2/day given by CI. Cycles were repeated every 28 days. Thirty eligible patients were entered in the study. The median number of cycles received was three. Grade IV neutropenia and thrombocytopenia occurred in 53% and 27% of patients, respectively. Among 30 treated patients, complete remission (CR) was seen in 2 patients and partial remission (PR) in 3 patients, for an overall response rate of 16.7% (95% confidence interval 6.8-32.4%). The median survival was 5.0 months (range: 0.3-32.4 months) and 16.7% and 10% of patients were alive at 1 and 2 years. respectively. Changes in the serum level of CA 19-9 provided an early marker of response which translated in differences in survival. Those with increasing or decreasing/stable levels of CA 19-9 after the first cycle of therapy had median survivals of 1.7 and 8.3 months, respectively (p = 0.0002). Although PACE chemotherapy produced durable responses in pancreatic cancer, the toxicity was substantial. A modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity. Also, the monitoring of the serum CA 19-9 level may provide a means to assess response and predict survival.
Adenocarcinoma↗
Pyogenic liver abscess: a geriatric problem.
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Age Distribution↗
Salmonella enterica serovar typhimurium surA mutants are attenuated and effective live oral vaccines.
A previously described attenuated TnphoA mutant (BRD441) of Salmonella enterica serovar Typhimurium C5 (I. Miller, D. Maskell, C. Hormaeche, K. Johnson, D. Pickard, and G. Dougan, Infect. Immun. 57:2758-2763, 1989) was characterized, and the transposon was shown to be inserted in surA, a gene which encodes a peptidylprolyl-cis, trans-isomerase. A defined surA deletion mutation was introduced into S. enterica serovar Typhimurium C5 and the mutant strain, named S. enterica serovar Typhimurium BRD1115, was extensively characterized both in vitro and in vivo. S. enterica serovar Typhimurium BRD1115 was found to be defective in the ability to adhere to and invade eukaryotic cells. Furthermore, S. enterica serovar Typhimurium BRD1115 was attenuated by at least 3 log units when administered orally or intravenously to BALB/c mice. Complementation of the mutation with a plasmid carrying the intact surA gene almost completely restored the virulence of BRD1115. In addition, S. enterica serovar Typhimurium BRD1115 demonstrated potential as a vaccine candidate, since mice immunized with BRD1115 were protected against subsequent challenge with S. enterica serovar Typhimurium C5. S. enterica serovar Typhimurium BRD1115 also showed potential as a vehicle for the effective delivery of heterologous antigens, such as the nontoxic, protective fragment C domain of tetanus toxin, to the murine immune system.
Administration, Oral↗
Phosphatidylinositol 3-kinase, Cdc42, and Rac1 act downstream of Ras in integrin-dependent neurite outgrowth in N1E-115 neuroblastoma cells.
Ras and Rho family GTPases have been ascribed important roles in signalling pathways determining cellular morphology and growth. Here we investigated the roles of the GTPases Ras, Cdc42, Rac1, and Rho and that of phosphatidylinositol 3-kinase (PI 3-kinase) in the pathway leading from serum starvation to neurite outgrowth in N1E-115 neuroblastoma cells. Serum-starved cells grown on a laminin matrix exhibited integrin-dependent neurite outgrowth. Expression of dominant negative mutants of Ras, PI 3-kinase, Cdc42, or Rac1 all blocked this neurite outgrowth, while constitutively activated mutants of Ras, PI 3-kinase, or Cdc42 were each sufficient to promote outgrowth even in the presence of serum. A Ras(H40C;G12V) double mutant which binds preferentially to PI 3-kinase also promoted neurite formation. Activated Ras(G12V)-induced outgrowth required PI 3-kinase activity, but activated PI 3-kinase-induced outgrowth did not require Ras activity. Although activated Rac1 by itself did not induce neurites, neurite outgrowth induced by activated Cdc42(G12V) was Rac1 dependent. Cdc42(G12V)-induced neurites appeared to lose their normal polarization, almost doubling the average number of neurites produced by a single cell. Outgrowth induced by activated Ras or PI 3-kinase required both Cdc42 and Rac1 activity, but Cdc42(G12V)-induced outgrowth did not need Ras or PI 3-kinase activity. Active Rho(G14V) reduced outgrowth promoted by Ras(G12V). Finally, expression of dominant negative Jun N-terminal kinase or extracellular signal-regulated kinase did not inhibit outgrowth, suggesting these pathways are not essential for this process. Our results suggest a hierarchy of signalling where Ras signals through PI 3-kinase to Cdc42 and Rac1 activation (and Rho inactivation), culminating in neurite outgrowth. Thus, in the absence of serum factors, Ras may initiate cell cycle arrest and terminal differentiation in N1E-115 neuroblastoma cells.
Cell Differentiation↗
Novel polymorphism in the coding region of the IL-13 receptor alpha' gene: association study with atopic asthma in the Japanese population.
Interleukin (IL)-4 and IL-13 play key roles in the development of atopic asthma. The IL-13 receptor (R) alpha' chain is a component of both IL-4R and IL-13R complexes. By screening the whole coding region of the IL-13Ralpha' gene for polymorphisms, we identified a new polymorphism at nucleotide position 1050 from the ATG start codon. The allelic frequency of the C/T polymorphism in the Japanese population was found to be 0.97:0.03. Because of the low frequency of the T allele, the association study failed to indicate any significant association between this polymorphism and atopic asthma in the Japanese population. Further studies are required in other racial groups with higher frequencies of this polymorphism to elucidate the association.
Alleles↗
Lack of association between CD28/CTLA-4 gene polymorphisms and atopic asthma in the Japanese population.
Atopic asthma occurs in genetically susceptible individuals in the presence of environmental factors. Recently, the costimulation signal from CD80-CD86 to CD28/CTLA-4 has been suggested to play an important role in the development of atopic asthma. In the present study, we analyzed three polymorphic regions within the CTLA-4 gene, an A/G substitution in exon 1 position 49, a C/T base exchange in the promoter position -318 and an (AT)n repeat polymorphism in the 3'-untranslated region of exon 4, and a CD28 gene polymorphism with a T/C substitution in intron 3 position +17 in 120 patients with atopic asthma and 200 normal controls. The polymorphism frequencies of CTLA-4/CD28 genes in patients did not differ from those in normal controls. Thus, the present study was unable to reveal any association between CTLA-4/CD28 gene polymorphisms and atopic asthma in the Japanese population.
Abatacept↗
The changing spectrum of Group B streptococcal (GBS) infection in infants of Saudi Arabia.
This study describes the incidence, clinical presentation and outcome of neonatal Group B streptococcal (GBS) infection in a Saudi Arabian Hospital. Charts of all neonates with GBS infection admitted to our hospital during a 5-year period (1990-1994) were reviewed retrospectively. Of the 29,601 live births, 23 neonates had GBS infection, giving an overall incidence rate of 0.8 per 1000 live births. The incidence rate appeared to increase from 0.2 per 1000 live births in 1990 to 1.2 per 1000 live births in 1994 (not statistically significant (P=0.07)). Of the 23 neonates with GBS infection, 16 (70%) were full term infants (gestation > or = 37 weeks). In contrast, 7 (30%) were preterm infants (gestation < 37 weeks). Ten (44%) mothers had premature rupture of membrane. Intrapartum fever and/or urinary tract infection was observed in 9% of the mothers. Nineteen (82%) of the neonates had early onset GBS infection, whereas only 4 infants (18%) had late-onset infection. Blood and CSF cultures were positive in 21 (91%) and 5 (21%), respectively. Complications of GBS infection were as follows: sepsis without focus of infection 15 (65%); meningitis 5 (22%); pneumonia 3 (13%); urinary tract infection 2 (9%). None of these complications had any significant association with the onset of infection (P>0.1). The overall case-fatality rate was 9%. The incidence of GBS infection appears to be increasing in Saudi neonates and measures to prevent perinatal transmission need to emphasized and implemented.
Adult↗
The management of alcohol-related seizures: an overview.
Alcohol-withdrawal seizures are one of the common medical emergencies. The seizures are generalized and usually occur abruptly between 6-8 hours after cessation of alcohol use (peak 12-24 hours). These patients are often uncooperative and therefore need careful assessment. Lorazepam is the first-line drug for termination and prophylaxis of alcohol-withdrawal seizures.
Adult↗
Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country.
A service for prenatal diagnosis of beta-thalassaemia was introduced in Pakistan in May 1994. Two renowned Islamic scholars, consulted before the service was introduced, ruled that a pregnancy can be terminated if the fetus is affected by a serious genetic disorder, and if termination is before 120 days (17 weeks) of gestation. During the first 3(1/2) years of the service 300 couples requested the test. Almost all the couples had been informed by their treating doctors. Most diagnoses were made between 10 and 16 weeks of gestation, and only 15 (5%) were reached after the 16th week. DNA analysis was by the amplification refractory mutation system (ARMS). A multiplex ARMS was developed in which three primer combinations identified the mutations in 91.5% of the couples. In 13 couples (4. 3%) linkage analysis was required for the fetal diagnosis. In 47/53 (88.7%) women carrying an affected fetus the pregnancy was terminated. In six cases it was declined principally on religious grounds. Postnatal confirmation of the prenatal diagnosis was possible in 117 unaffected children. One year after the start of the service, interviews with 141 couples with an affected child showed that 72% knew of the availability of prenatal diagnosis. Thirty-two of the informed couples had had a pregnancy, but only 18 (56%) used prenatal diagnosis. The main reasons for non-utilization of prenatal diagnosis were the cost of the test and fear of undergoing the test, though some gave no clear explanation. This study demonstrates that prenatal diagnosis is feasible and acceptable in a Muslim country such as Pakistan.
Attitude↗
Temporary balloon occlusion of internal carotid artery : a simple and reliable clinical test.
Balloon test occlusion of internal carotid artery has been frequently used in preoperative evaluation of patients with carotid aneurysms, fistulas and skull based neoplasms in whom arterial sacrifice is planned or considered as a possible part of therapy. We present our experience of the test in 28 patients. The test was positive in four and negative in twenty four patients. The results are compared with cross-compression angiography and the outcome following internal carotid artery sacrifice. There were no complications related to the test and the results accurately predicted the tolerance to occlusion of artery. We found the test safe, simple to perform and reliable to preoperatively detect patients at risk of ischaemic stroke following surgical ligation or endovascular occlusion of internal carotid artery.
Adolescent↗
Distribution of tuberculosis cases in inner cities.
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Female↗
Improved indicators of infant mortality for integrated primary healthcare programmes.
Mortality and fertility rates are decreasing rapidly in many developing countries. It is argued that the indices commonly used as measures of these changes, i.e. infant mortality rate and fertility rate, ignore the interaction between mortality and fertility, and do not reflect their combined impact in lowering overall infant mortality. The paper proposes new indicators of infant mortality, termed fertility-adjusted infant mortality ratio (FIMR), age-specific, fertility-adjusted IMR (AFIMR), and total infant mortality ratio (TIMR) that are more sensitive to rapid demographic changes. These indicators include the combined effects of changes in both fertility and infant mortality rates on overall infant mortality in a region and appear to measure the effects of integrated health programmes better. Further, these conceptualize the mother-infant pair as an appropriate unit with which to monitor mortality, and may be used for guiding allocation of resources intended to lower infant mortality. The application and usefulness of these indicators have been illustrated, using one hypothetical example and empirical data from the maternal-child health and family-planning programme in Matlab, Bangladesh, as well as data from white and black population groups in the U.S.A. The results of these examples demonstrate that the new indicators are more sensitive than traditional measures when describing infant mortality, and may better reflect the perception in infant mortality status in the community.
Adolescent↗
Massive pelvic hemangioma in a patient with blue rubber bleb nevus syndrome.
Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by gastrointestinal and cutaneous hemangiomas. Patients typically present with gastrointestinal bleeding and anemia. Management of gastrointestinal bleeding may be challenging, since these lesions may be diffusely distributed throughout the gastrointestinal tract. The most common location is the small bowel, and recurrence is common. We describe a patient with BRBNS and lower gastrointestinal bleeding resulting from a large pelvic hemangioma eroding into the rectal wall.
Adult↗
Do health care workers need to wear masks when caring for patients with pulmonary tuberculosis?
Outbreaks of hospital acquired tuberculosis (TB) in the 1990s, some of which affected staff, highlight the fact that TB still poses a risk to health care workers (HCWs). This risk is best minimised by the primary controls of early identification and treatment, good infection control practice such as early isolation, patients covering mouths when coughing, and engineering controls such as negative pressure isolation. There is no direct evidence to prove that the use of respiratory protective devices has prevented HCWs from acquiring TB, but modelling has shown that environmental controls are not enough to prevent exposure. Masks that filter aerosols (including TB) and have at least 95% efficiency of filtering particles 0.3 micron in diameter can reduce exposure. Environmental controls in the United Kingdom (UK) do not (always) include a specified minimum number of air-changes per hour or negative pressure. Therefore it seems reasonable to advise that HCWs should use masks as advocated by national guidelines for high risk procedures. Masks are also of value when entering any body cavity or dissecting any viscus/organ in which TB is suspected, as in the necropsy room or operating theatre. This is recommended in current guidelines from the United States but not those from the UK.
Guidelines as Topic↗
Endothelial cell E- and P-selectin up-regulation in murine contact sensitivity is prolonged by distinct mechanisms occurring in sequence.
The selectins are adhesion molecules that mediate the tethering and rolling of leukocytes on vascular endothelium. Although E-selectin and P-selectin are known to be expressed by endothelial cells (EC) in response to proinflammatory stimuli, their pattern and mechanisms of expression in immune-mediated inflammation remain poorly understood. By quantifying luminal endothelial selectin expression via i.v. administration of radiolabeled mAb, we detected constitutive expression of P-selectin, but not E-selectin, in mouse skin. Both selectins were transiently up-regulated after intradermal TNF-alpha, IL-1alpha, or IL-1beta. In contrast, during a contact sensitivity response to oxazolone, expression of both selectins was prolonged, with distinct peaks at 6 and 48 h. Experiments with P-selectin gene-targeted mice showed that the P-selectin measured was exclusively expressed by EC rather than platelets. The early and late phases of selectin expression in contact sensitivity were differentiated in terms of their requirement for prior sensitization, and the action of IL-1. Whereas the early phase was a nonspecific 'irritant' response to oxazolone, the late phase was Ag specific and was partially IL-1 dependent. Therefore, persistence of both E- and P-selectin expression in vivo can occur as a result of sequential and distinct EC activation processes that appear to be at least partially different from those previously reported as stimulating ICAM-1 and VCAM-1 expression. The further elucidation of mechanisms of EC activation in this model may help determine the relative roles of selectins and ligands for leukocyte integrins in the sequential recruitment of T cells and other leukocyte subsets during ongoing immune-mediated inflammatory responses.
Animals↗