Applying for preregistration posts in scotland
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Journal Article↗
Biomedical subjects
A Hussain
Publications and source records attributed to A Hussain.
Detection of TNFalpha expression in the bone marrow and determination of TNFalpha production of peripheral blood mononuclear cells in myelodysplastic syndrome.
TNFalpha is a highly active cytokine which plays an important role in the regulation of apoptotic cell death, a mechanism involved in the pathophysiology of myelodysplastic syndrome (MDS). In this study we investigated the expression of TNFalpha of the bone marrow trephine biopsies by immunohistochemical method and the TNFalpha production of peripheral blood mononuclear cells by ELISA method in 15 patients affected by MDS. Five of seven patients without excess of blasts showed high or intermediate TNFalpha expression in the bone marrow biopsies, whereas two patients with excess of blasts were negative and one had low expression. The five CMML patients revealed low or intermediate expression. The production of TNFalpha by the PBMC was analysed in 10 patients, four patients with RA and two with CMML produced higher level of TNFalpha which increased after stimulation with phorbol myristic acetate, but none of the RAEB patients revealed increase in TNFalpha production. In conclusion we suppose that increased TNFalpha expression and production by PBMC may be an indirect evidence of the role of increased apoptosis in low risk MDS patients.
Adult↗
No difference in serum sialic acid in type 2 diabetic patients from the United Arab Emirates with and without diabetic retinopathy.
Serum total sialic acid (TSA) has recently been shown to be related to diabetic retinopathy. However, there is some controversy as this may be true in European Type 2 diabetic patients but not South Asians. There are few data looking at serum TSA expression in Arab Type 2 diabetic patients from the United Arab Emirates (UAE) and we wished to test the hypothesis that there may be different serum TSA expression in Arab Type 2 diabetic patients as regard to retinopathy. Sixty-five Type 2 diabetic patients from the UAE were studied (19 male and 46 female, age 57.5+/-9.8 (45-74) years, duration of diabetes 9.4+/-5.7 (0-22) years. The serum TSA in 13 patients with diabetic retinopathy was 757+/-130 mg/l and 782+/-163 mg/l in those without retinopathy (NS). There was no significant correlation between serum TSA and patient age, serum fructosamine, diabetes duration, or blood pressure. As in South Asians serum TSA does not appear to be elevated in Type 2 diabetic patients from the United Arab Emirates with diabetic retinopathy.
Aged↗
In vitro effects of sildenafil and phentolamine, drugs used for erectile dysfunction, on human sperm motility.
OBJECTIVE: The aim of this study was to determine the effects of sildenafil and phentolamine on sperm motility in vitro. STUDY DESIGN: Semen or washed sperm was mixed with various doses of sildenafil or phentolamine and analyzed for motility during a 30-minute period. The pH was measured for each of the samples tested. Statistical analyses were performed with analysis of variance. RESULTS: A 200-microg/mL dose of sildenafil had no effect on sperm motility. However, the highest dose (2000 microg/mL) significantly reduced motility by about 50%. The pH was reduced in this high-dose sample. The lowest dose of phentolamine (20 microg/mL) had no effect, whereas a dose of 200 microg/mL resulted in a significant reduction in sperm motility. The highest dose (2000 microg/mL) stopped virtually all sperm from moving. CONCLUSION: This study demonstrated a direct dose-related effect of phentolamine on reducing sperm motility. Only the highest dose of sildenafil had an effect, which may have been caused by a decline in pH.
Dose-Response Relationship, Drug↗
Involvement of Sarco/endoplasmic reticulum Ca(2+) ATPases in cell function and the cellular consequences of their inhibition.
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Adaptation, Physiological↗
Cloning and characterization of a human genotoxic and endoplasmic reticulum stress-inducible cDNA that encodes translation initiation factor 1(eIF1(A121/SUI1)).
We report the cloning and characterization of a DNA damage-inducible (DDI) transcript DDI A121. The full-length human DDI A121 cDNA contains an open reading frame of 113 amino acids, corresponding to a protein of 12.7 kDa. The deduced amino acid sequence of A121 shows high homology to the yeast translation initiation factor (eIF) sui1 and also exhibits perfect identity to the partial sequence of recently purified human eIF1. Expression of human A121 corrected the mutant sui1 phenotype in yeast, demonstrating that human A121 encodes a bona fide translation initiation factor that is equivalent to yeast sui1p. The mammalian A121/SUI1 gene exhibits two transcripts (1.35 kilobases and 0.65 kilobases) containing a common coding region but differing in their 3'-untranslated region. The long and short A121/SUI1 mRNAs are differentially regulated by genotoxic and endoplasmic reticulum stress. The genotoxic stress induction of A121/SUI1 mRNA is conserved in both humans and rodents and occurs in a p53-independent manner. Our identification of a stress-inducible cDNA that encodes eIF1 suggests that modulation of translation initiation appears to occur during cellular stress and may represent an important adaptive response to genotoxic as well as endoplasmic reticulum stress.
Amino Acid Sequence↗
Effects of various amino acid 256 mutations on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase function and their role in the cellular adaptive response to thapsigargin.
Upon direct selection of mammalian cells for resistance to thapsigargin (TG), a potent inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase (SERCA), the ATPase can acquire specific mutations at amino acid position 256 (aa256). In particular, Phe256 --> Leu and Phe256 --> Ser substitutions can occur upon TG selection, with each substitution resulting in a SERCA that is 4- to 5-fold resistant to TG inhibition (M. Yu et al., J. Biol. Chem. 273, 3542-3546, 1998). We have now identified a third substitution, i.e., Phe256 --> Val, that occurs when the Chinese hamster lung fibroblast cell line DC-3F is selected for TG resistance. Although the Phe256 --> Val substitution at codon 256 results in a SERCA whose enzymological properties in terms of Ca2+ transport and ATP hydrolysis are essentially similar to that of wild-type (wt) SERCA, the mutant enzyme is more than 40-fold resistant to TG inhibition. To analyze further the role of aa256 in TG-SERCA interactions, mutational analysis of this particular residue was also carried out. Of all the mutations introduced, only the Phe256 --> Glu substitution interferes with expression of the ATPase. The Phe256 --> Arg substitution does not interfere with SERCA expression, but the resulting enzyme is totally inactive. In terms of sensitivity of the various mutants to TG, maximal reduction in the ATPase's affinity for TG occurs with amino acid substitutions containing branched side chains, i.e. with the Phe256 --> Val, Phe256 --> Ile, and Phe256 --> Thr mutants. Since a corresponding Phe is conserved in the Na+, K+-ATPase which is not sensitive to TG, our findings suggest that this amino acid provides stabilization of the stalk segment with respect to the membrane interface, thereby optimizing specific interactions of TG with neighboring S3 residues (L. Zhong and G. Inesi, J. Biol. Chem. 273, 12994-12998, 1998). It is likely that a relatively high frequency of codon 256 mutations favor the aa256 mutants as a specific adaptive response to TG selection.
ATP Binding Cassette Transporter, Subfamily B↗
Bax is frequently compromised in Burkitt's lymphomas with irreversible resistance to Fas-induced apoptosis.
We have analyzed the Fas-mediated death pathway in a panel of 11 Epstein-Barr virus (EBV)-negative and 10 EBV-positive Burkitt's lymphoma (BL) cell lines. We show that the increased expression of Fas in EBV-positive cell lines is mediated via LMP-1. Four of the 21 BL cell lines are readily responsive to Fas-mediated cell death signals. Of the remaining 17 cell lines, 10 can be sensitized by up-regulating Fas either via exogenous expression of LMP-1 or via treatment with CD40L. These same cell lines can also be sensitized by treatment with cycloheximide (CHX), which, however, does not result in up-regulation of Fas. Neither up-regulation of Fas, nor treatment with CHX, restore Fas sensitivity in seven BL cell lines. Further analyses indicated that 5 of the 7 cell lines (and none of the 14 responsive cell lines) were also compromised in the integrity/expression of the proapoptotic gene Bax. Thus, in most BL cell lines, the Fas pathway seems to be inhibited, although the mechanism of inhibition varies. The correlation between Bax mutation and irreversible (by CD40L or CHX) Fas resistance raises the possibility, for the first time, that Bax may play a critical function in Fas-mediated cell death in BL.
Animals↗
Improved clinical outcomes in patients undergoing coronary artery bypass grafting with coronary endarterectomy.
BACKGROUND: Coronary artery bypass grafting (CABG) with coronary endarterectomy (CE) has been associated with increased morbidity and mortality. We sought to evaluate the impact of recent advances in operative and perioperative management on outcomes after CE. METHODS: One hundred fifty-one consecutive patients undergoing first-time CABG with CE between 1991 and 1997 were compared with a concurrent group of 757 patients undergoing CABG without CE (Control). RESULTS: Age, gender, left ventricular ejection fraction, percent nonelective were similar in both groups. Compared with control, the CE group had a higher incidence of hypertension (80% versus 71%, p = 0.02), diabetes (42% versus 32%, p = 0.01), prior myocardial infarction (MI) (68% versus 59%, p = 0.05), peripheral vascular disease (36% versus 16%, p < 0.001), renal failure (15% versus 4%, p < 0.001), and three-vessel coronary disease (81% versus 70%, p = 0.007), resulting in higher Society of Thoracic Surgeons database predicted mortality (4.9+/-5.9% versus 3.9+/-4.6%, p = 0.05). Despite the higher risk profile of the CE group, hospital mortality (CE 2.0%, Control 1.2%) and the incidence of major complications such as cerebrovascular accident (CVA) (0.7% versus 1.5%), major respiratory complications (8% versus 5%), and postoperative MI (3% versus 1.4%) were similar between the groups (all p = NS). In a multiple logistic regression analysis, prolonged cardiopulmonary bypass time was an independent predictor of postoperative MI (odds ratio 1.2, CI 1.05 to 1.39, p < 0.01) and the use of heparin-bonded cardiopulmonary bypass circuits of reduced MI rate (odds ratio 0.25, CI 0.08 to 0.76, p < 0.01). Mean follow-up for 94% of patients was 30+/-19 months (range 1 to 83 months). Five-year survival after CE was 70+/-5%, with 96% of patients in Canadian Cardiovascular Society class I/II. CONCLUSIONS: In a contemporary series of carefully selected patients, mortality and major complications after CE are now similar to CABG without CE. CE itself is not an independent predictor of postoperative MI. Functional class of hospital survivors is excellent.
Aged↗
Clinical usefulness of Doppler spectral analysis of graft dysfunction in living-related donor renal transplants.
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Cyclosporine↗
Tubulointerstitial nephritis associated with minimal self reexposure to rifampin.
We report the case of a 27-year-old Asian man who self-medicated with two capsules of rifampin 1 year after completing a continuous course of chemotherapy for tuberculosis that included that drug. He developed flank pain and edema and presented with uremia requiring dialysis; despite this, he had a serum potassium of only 3.5 mEq/L. Renal biopsy showed interstitial infiltrate with inflammation of the tubules. Renal function began to improve after a 3-week course of prednisone. This case is remarkable for the severity of the renal failure despite such a minimal self-exposure.
Acute Disease↗
Elevation of serum cardiac troponin I in noncardiac and cardiac diseases other than acute coronary syndromes.
This study evaluated the role of serum cardiac troponin I as a biochemical marker for the diagnosis of acute coronary syndromes in the presence of noncardiac diseases. Diagnostic characteristics were examined in 102 consecutive patients who were found to have serum cardiac troponin I levels higher than the upper reference limit of 0.6 ng/mL. Of 102 patients with cardiac troponin I levels of >0.6 ng/mL, 35 did not have the final diagnoses of acute coronary syndromes (myocardial infarction or unstable angina) but had various other final diagnoses, including nonischemic dilated cardiomyopathy, muscular disorders, central nervous system disorders, HIV disease, chronic renal failure, sepsis, lung diseases, and endocrine disorders. The mean value of serum cardiac troponin I in the patients with diseases other than acute coronary syndromes was significantly lesser than in those with acute coronary syndromes (2.0+/-1.9 [SD] v. 24.7+/-28.2 ng/mL; P<.0001). There were significantly fewer histories of chest pain and prior myocardial infarction in patients with diseases other than acute coronary syndromes than in those with acute coronary syndromes (history of chest pain, 3 v. 48 patients [P<.001]; history of prior myocardial infarction, 0 v. 30 patients [P<.001]). In conclusion, elevated serum levels of cardiac troponin I, especially in the lower ranges, should be interpreted with caution, particularly in patients suffering from acute illnesses who lack other diagnostic features suggestive of acute coronary ischemic events.
Acute Disease↗
In vitro protein adsorption to 2 intraocular lens materials.
PURPOSE: To study in vitro protein adsorption to poly(methyl methacrylate) (PMMA) and foldable AcrySof intraocular lenses (IOLs). SETTING: Department of Ophthalmology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, United Kingdom. METHODS: Poly(methyl methacrylate) (Alcon Surgical, model MC60BM) and AcrySof (Alcon Surgical, model MA60BM) IOLs were incubated in physiological concentrations of radiolabeled albumin or fibronectin at 37 degrees C for periods between 5 minutes and 1 week. The IOLs were removed and rinsed in buffered saline, and the amount of adsorbed protein was calculated by measuring the radioactivity with scintillation spectrometry. RESULTS: The adsorption of both proteins occurred rapidly over the first 2 hours; the rate of adsorption was concentration dependent. Quantitative differences were found: PMMA lenses bound significantly greater quantities of albumin. Initial fibronectin adsorption to both materials was similar, but increased adsorption to AcrySof IOLs was found at days 1 and 7. CONCLUSIONS: The differences in protein absorption to PMMA and AcrySof IOLs in vitro may contribute to the differences in the biological response to these IOLs, including the lower rates of posterior capsule opacification associated with acrylic lenses.
Acrylic Resins↗
Para-incisional tattooing with electrocautery.
The authors present a technique using electrocautery diathermy to make surgical tattoos. This method has been used in over 300 patients who underwent head and neck surgery at Aberdeen Royal Infirmary and Albany Medical College, New York, over a period of five years. A wide variety of operative procedures such as total laryngectomies and neck dissections were performed. The electrocautery surgical tattoos have a major advantage of persisting until the end of the operative procedure by which time other types of tattoos have faded. The technique is widely available, inexpensive, and has to date been complication free.
Electrocoagulation↗
Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy.
The purpose of this study was to examine the effect of pre-treatment anaemia on tumour recurrence and survival in patients treated with primary radiotherapy for early squamous cell carcinoma of the larynx. A retrospective analysis of 117 patients with previously untreated T1N0M0 and T2N0M0 squamous cell carcinoma of the larynx was carried out. Patients were considered anaemic if their pre-treatment haemoglobin levels were below 13 g/dl in males and 11.5 g/dl in females. The influence of pre-treatment haemoglobin levels on local control and survival were evaluated using Cox proportional hazards regression models. Two- and five-year local-regional control estimates for anaemic patients were 58 per cent and 53 per cent respectively while patients with normal haemoglobin levels had two and five-year local-regional control rates of 90 per cent and 81 per cent respectively (p = 0.002). Multivariate Cox regression analysis showed pre-treatment haemoglobin significantly influencing recurrence-free survival (p = 0.0094). Patients with a low haemoglobin level prior to radiation therapy suffered higher levels of local-regional failure.
Adult↗
Artificial neural networks applied to the in vitro-in vivo correlation of an extended-release formulation: initial trials and experience.
Artificial neural networks applied to in vitro-in vivo correlations (ANN-IVIVC) have the potential to be a reliable predictive tool that overcomes some of the difficulties associated with classical regression methods, principally, that of providing an a priori specification of the regression equation structure. A number of unique ANN configurations are presented, that have been evaluated for their ability to determine an IVIVC from different formulations of the same product. Configuration variables included a combination of architectural structures, learning algorithms, and input-output association structures. The initial training set consisted of two formulations and included the dissolution from each of the six cells in the dissolution bath as inputs, with associated outputs consisting of 1512 pharmacokinetic time points from nine patients enrolled in a crossover study. A third formulation IVIVC data set was used for predictive validation. Using these data, a total of 29 ANN configurations were evaluated. The ANN structures included the traditional feed forward, recurrent, jump connections, and general regression neural networks, with input-output association types consisting of the direct mapping of the dissolution profiles to the pharmacokinetic observations, mapping the individual dissolution points to the individual observations, and using a "memorative" input-output association. The ANNs were evaluated on the basis of their predictive performance, which was excellent for some of these ANN models. This work provides a basic foundation for ANN-IVIVC modeling and is the basis for continued modeling with other desirable inputs, such as formulation variables and subject demographics.
Computer Simulation↗
Determinants of mortality among children in the urban slums of Dhaka city, Bangladesh.
The growing slum population in the developing world is an increasing challenge for local health authorities. Little is known of the patterns of disease occurrence including treatment types offered in this population. The paper describes reported child mortality and its determinants, including the main diseases affecting children and treatments, in the slum population of Dhaka city, Bangladesh. 1500 households in three slum communities were included in a cross-sectional survey. Reported death rates in the households per 1000 children (0-107 months) within the last year from the interview were 20.5 for boys and 27.0 for girls. More girls than boys died in infancy (age < 12 months). The most frequent reported causes of deaths were tetanus in infancy and diarrhoea among children aged < or = 12 months. Vaccination coverage (DPT, polio, measles and BCG) was 73% for children < 3 years of age. The results showed that gender difference in mortality may have been influenced by the patterns of treatment received during sickness and the choice of treatment was determined by the financial ability of the households. Household income, children's vaccinations, TT immunization of mothers and personal cleanliness appeared to be significantly associated with child mortality. Despite the relatively high vaccination coverage for this population, child mortality remained alarmingly high, indicating that socioeconomic and environmental conditions must be improved to substantially reduce morbidity and mortality in this population.
Accidents↗
Congenital rhabdomyosarcoma.
A congenital rhabdomyosarcoma presented as a partially necrotic mass on the left forearm on delivery at term. Ulceration and persistent bleeding were managed by primary curettage followed by local resection including partial excision of the muscles of the extensor compartment of the forearm. The defect was resurfaced with a split skin graft. The surgery was followed by chemotherapy according to the IVA regime. There was no recurrence at 2 years of age and the limb was fully functional. The presentation and management of rhabdomyosarcoma are discussed.
Female↗