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Biomedical subjects

N Khan

Publications and source records attributed to N Khan.

At least 163 records · Page 9Linked to original sources

Responding to cough: Boholano illness classification and resort to care in response to childhood ARI.

A qualitative study into the health seeking behaviour of caretakers in response to ARI in children under five years of age was conducted in the province of Bohol, the Philippines. The study was designed to compliment survey data generated from a long running ARI intervention project, specifically to explain behaviours identified as problematic by the project. Results indicate the importance of folk diagnosis as a basis for selection of first resort for care in the management of childhood ARI. A cultural category, piang, was identified as a major factor influencing health seeking behaviour and delay in consulting the biomedical system where serious ARI exists. In addition, caretakers' financial situation and social contacts are important in their decision to seek biomedical assistance and are often implicated in delay in presentation and acting upon referral to hospital.

Acute Disease↗

Ocular health status of chemical industrial workers.

BACKGROUND: Approximately 1.2 million workers are employed within chemical industries throughout South Africa. Very little basic data exists regarding the ocular health status and prevalence of occupationally related eye disorders of these workers. METHOD: A questionnaire was administered and an ocular health examination was carried out on 78 workers in a chemical factory. Workers and the ocular disorders found were then classified according to those exposed and those not exposed to chemicals. RESULTS: Ocular disorders were more prevalent in exposed workers (73.1%) than in nonexposed workers (43.6%). Statistically significant differences between exposed and nonexposed workers were found with respect to the prevalence of certain anterior segment disorders, viz., tear disorders, dry eye conditions, allergic conjunctivitis, and conjunctival melanosis. In respect to the prevalence of ocular disorders found, 40.8% were attributed to occupational exposure to chemicals. CONCLUSION: This pilot study shows that further research is required to explore the cause-effect relation between chemical exposure and development of certain anterior segment disorders. Occupational exposure to chemicals should be reduced and exposure protocols at work need to be revised in order to reduce the prevalence of occupationally related eye disorders.

Adult↗

[Antibody response, cortisolemia and prolactinemia in rainbow trouts].

We have studied the humoral immune response (production of anti-Yersinia ruckeri antibodies), and measured the levels of plasmatic hormones (cortisol and prolactin) in rainbow trout (Oncorhynchus mykiss) subjected to hyperosmotic stress (NaCl, 22 / 1000). Under acute stressful conditions (saline stress during 7 days), high blood cortisol and prolactin (PRL) levels were correlated with a weak anti-Yersinia ruckeri antibody response, as evidenced by late and low antibody titres as compared to normal fish. Interestingly, the group of fish subjected to chronic stress (till 30 days) exhibited no significant differences in blood cortisol and prolactin levels despite low antibody titres as compared to control group. Hence, it is possible that in acute stress, cortisol and prolactin levels might exert immunosuppressive effects on antibody production, whereas in chronic stress other neuroendocrine hormones might result in curtailed humoral immunity.

Adaptation, Physiological↗

5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down-regulation.

The connection between agonist-induced desensitization and down-regulation of 5-hydroxytryptamine2A (5-HT2A) receptors was examined in a clonal cell line that stably expresses the 5-HT2A receptor. Brief (2-hr) and prolonged (24-hr) exposure to the agonist quipazine or the agonist 4-iodo-(2,5-dimethoxy)- phenylisopropylamine (DOI) diminished 5-HT2A receptor-mediated phosphoinositide hydrolysis; no change in 5-HT2A receptor number or affinity was measured after 24 hr of exposure to DOI or quipazine. Immunohistochemical studies demonstrated that a 24-hr exposure to DOI did not alter surface 5-HT2A receptor immunoreactivity. Western blot analysis with G alpha q- and G alpha 11-selective antibodies indicate that a 24-hr agonist exposure did not alter the levels of phospholipase C-dependent G proteins. These results suggest that desensitization after prolonged DOI exposure can occur via a process independent of the levels of phospholipase C-coupled G proteins. Studies with a mutant 5-HT2A receptor (F340L) indicated that binding per se is not sufficient for desensitization. Down-regulation of the protein kinase C isozymes alpha and epsilon by overnight exposure to phorbol-12,13-dibutyrate attenuated the intermediate phase (i.e., after 2-6 hr of agonist exposure) of DOI- and quipazine-induced desensitization. These results indicate that the intermediate phase of DOI-induced desensitization is mediated by the alpha- and/or epsilon-protein kinase C isozymes but that neither is involved in the later phase (i.e., after 24 hr of agonist exposure) of desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Cytokine regulation of endothelin-1 release from bovine aortic endothelial cells.

The action of cytokines on the endothelium is a pivotal event in a number of vascular pathologies and inflammatory conditions. Here we have tested the effect of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-2 on endothelial-1 (ET-1) release from cultured bovine aortic endothelial cells. TNF-alpha and IL-1 beta caused concentration-dependent increases in ET-1 release. IL-2 up to concentrations of 100 ng/ml did not stimulate ET-1 release. The induction of ET-1 synthesis by cytokines may be of underlying importance in the endothelial cell dysfunction observed in a number of vascular diseases.

Animals↗

Ambulatory blood pressure and heart rate in adolescents with insulin-dependent diabetes mellitus.

There is little information regarding ambulatory blood pressure in adolescents with insulin-dependent diabetes. Twenty-four-hour ambulatory blood pressure and heart rate was studied in 28 normotensive adolescents with insulin-dependent diabetes mellitus (IDDM) and normoalbuminuria, and adolescent controls. Ambulatory heart rate was higher during day and night (P = .001) in the IDDM patients, with normal mean diurnal variation of heart rate and blood pressure. Duration of diabetes related to diastolic ambulatory blood pressure (r = 0.69, P = .0001) and diastolic blood pressure burden (r = 0.61, P = .0001) independent of age, gender, height, body mass index, metabolic control, and albumin excretion rate. The ambulatory blood pressure monitor was well accepted in patients and controls. Ambulatory blood pressure monitoring in adolescents detects early changes in relation to duration of insulin-dependent diabetes.

Adolescent↗

Limbic encephalitis: a case report.

We report a case of a 24 year old patient, who presented with simple and complex partial epileptic seizures, progressive changes in behaviour and affect including marked aggression, and a decline in memory to the point of inability to learn. Extensive work-up resulted in a final diagnosis of limbic encephalitis. This diagnosis was supported by a number of investigations performed during the follow-up of 6 years and ranging from the basic EEG to the more sophisticated investigations of magnetic resonance tomography, magnetoencephalography and positron emission tomography.

Adult↗

A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, and efficacy.

BACKGROUND: Previous clinical trials have shown that the use of recombinant human erythropoietin (EPO) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation. However, the role of EPO therapy in nonanemic patients remains undefined. To identify this role, a randomized, controlled, multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent (0.39). STUDY DESIGN AND METHODS: EPO (150, 300, or 600 units/kg) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period. Sixteen (14%) of 116 patients were unable to complete the treatment protocol because of adverse events (n = 11) or for personal reasons (n = 5); 2 patients (1 EPO and 1 placebo) experienced serious adverse events. RESULTS: In 91 evaluable patients, additional red cell production during the study period was 440 +/- 176, 621 +/- 215, 644 +/- 196, and 856 +/- 206 mL (mean +/- SD), respectively, for patients receiving placebo and EPO at 150, 300, and 600 units/kg (p < 0.05 for all EPO groups compared to placebo). However, the percentages of patients in each group who received allogeneic blood did not differ: 2 (9%) of 23 placebo patients and 6 (9%) of 68 EPO patients. CONCLUSION: It is concluded that, while EPO therapy increased preoperative red cell production, no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation.

Adolescent↗

Mammary ductal epithelial cell hyperproliferation and hyperplasia induced by a nutritional stress diet containing four components of a western-style diet.

We have studied effects of several nutrients on the proliferation of mammary ductal epithelial cells in C57BL/6J virgin female mice, using morphometry and [3H]dT in vivo labeling. A nutritional stress diet was given based on the AIN-76A semi-synthetic diet modified to contain four significant risk factors of a Western-style diet: high fat and phosphate and decreased calcium and vitamin D. The numbers of large, intermediate and terminal ducts and proliferating epithelial cells in mammary glands were assayed in control and stress diet groups. An increased number of mammary ducts and increased number of proliferating cells were found at the level of the small terminal ducts, a cancer-prone region in the mammary gland in the stress diet group compared to the control group after 20 weeks of diet administration. Thus, mammary terminal ductal hyperproliferation, expansion in the size of the proliferative epithelial cell compartment and excessive duplication of mammary ductal epithelial cells were found after this Western-style diet containing decreased dietary calcium and vitamin D. These changes are similar to those developing in colonic epithelium of mice maintained on the same diets and during chemically induced colonic carcinogenesis.

Animals↗

Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy.

Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150 U/kg, n = 16, 300 U/kg, n = 18, or 600 U/kg, n = 19) or placebo (n = 18). Using data from the three preoperative study visits, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO-treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia.

Adult↗

Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride.

We investigated in vivo D2 receptor binding using 11C-raclopride and PET in the striatum of 17 subjects with the narcoleptic syndrome. Putamen and caudate nucleus 11C-raclopride uptake was comparable in the total patient group and controls, and the tracer uptake was similar in the HLA-DR2-positive (n = 12) and HLA-DR2-negative (n = 5) narcoleptic subjects. There was a significant increase in 11C-raclopride uptake in the putamen of narcoleptic subjects older than 31 years (n = 11) when compared with age-matched controls (n = 15). There was no evidence of involvement of the striatal D2 dopaminergic neurotransmitter system in the basic pathophysiology of the narcoleptic syndrome despite an age-related increase in putaminal 11C-raclopride uptake.

Adolescent↗

Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy.

We have studied 25 patients with interictal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after selective surgery for temporal lobe epilepsy (TLE). Based on the findings of the presurgical evaluation, including ictal intracranial EEGs, histopathologic findings, and the postoperative outcome, we classified the patients in three subgroups: (1) patients with TLE of lateral temporal origin (n = 5), (2) patients with mesiobasal limbic TLE associated with mesial gliosis (n = 14), and (3) patients with mesiobasal limbic TLE and small mesial tumors (n = 6). Postoperatively, patients with mesiobasal limbic TLE and mesial gliosis and five of six patients with mesiobasal limbic TLE and mesial tumors were seizure-free; the remaining sixth patient had one generalized seizure. Patients with TLE of lateral temporal origin had more than 90% reduction of seizure frequency. The main postoperative metabolic findings were as follows: (1) marked increase of regional cerebral metabolic rate of glucose (rCMRglu), both in the ipsilateral and, significantly, in the contralateral hemisphere in patients with mesiobasal limbic TLE and mesial gliosis-the changes of brain metabolism were characteristic for patients with the syndrome of "mesial temporal lobe epilepsy" (MTLE); (2) decrease of rCMRglu values in the contralateral mesiobasal temporal lobe (TL) cortex in all patient groups--the reduction of rCMRglu in homologous brain structures contralateral to the operated side provides evidence for stronger interhemispheric connections between both mesial TL structures than were hitherto supposed; and (3) a trend toward a normalization of rCMRglu values in the ipsilateral temporal neocortex 12 months after surgery in patients with MTLE syndrome.

Adolescent↗

Low-birth-weight infants show earlier onset of IDDM.

OBJECTIVE: Pancreatic beta-cell mass increases rapidly during gestation and early infancy. Infants who are small for gestational age, which is a marker for poor intrauterine nutrition, have reduced beta-cell mass. We examined whether weight and length in early infancy, and in inference beta-cell mass, is related to age at onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Data from infant records of 232 patients with IDDM, including birth weight, birth length, gestational age, weight at 6 months of age, and feeding history during the first 6 months of life, were analyzed. Maternal recall was not used for data collection. RESULTS: Low-birth-weight infants (<2.5 kg) showed a significantly earlier onset of diabetes (4.3 [3.2-6.0] years vs. 9.0 [5.3-11.8] years, median [25-75th percentile]; P < 0.0001). Infants small for gestational age also had earlier onset than those with birth weight above the 10th percentile after correction for gestational age (6.2 [3.6-10.5] vs. 9.2 [5.4-11.8] years; P < 0.0001). Infants with corrected birth weight: length ratio below the 10th percentile had earlier onset, as did infants with corrected 6-months weight below the 10th percentile (4.9 [2.8-6.0] years vs. 8.8 [5.2-11.8] years; P < 0.0001). Infants who were exclusively breast-fed for 6 months showed a slightly later onset of diabetes than those who were bottle- or mixed-fed, independent of weight (9.4 [5.0-11.3] years vs. 8.3 [4.2-11.7] years; P < 0.0001). CONCLUSIONS: Weight and growth parameters in utero and early infancy may influence the age at onset of IDDM. beta-cell mass is likely to be a significant factor.

Age of Onset↗

Validity of the ten questions screened for childhood disability: results from population-based studies in Bangladesh, Jamaica, and Pakistan.

An international study to validate the Ten Questions screen for serious childhood disability was undertaken in communities in Bangladesh, Jamaica, and Pakistan, where community workers screened more than 22,000 children ages 2-9 years. All children who screened positive, as well as random samples of those who screened negative, were referred for clinical evaluations. Applying comparable diagnostic criteria, the sensitivity of the screen for serious cognitive, motor, and seizure disabilities is acceptable (80-100%) in all three populations, whereas the positive predictive values range from 3 to 15%. These results confirm the usefulness of the Ten Questions as a low-cost and rapid screen for these disabilities, although not for vision and hearing disabilities, in populations where few affected children have previously been identified and treated. They also show that the value of the Ten Questions for identifying disability in underserved populations is limited to that of a screen; more thorough evaluations of children screened positive are necessary to distinguish true- from false-positive results and to identify the nature of the disability if present.

Bangladesh↗

Fatal sepsis due to Pseudomonas cepacia.

Pseudomonas cepacia is known as an opportunistic pathogen in the patients with altered host defence. We report a case of hospital-acquired fatal sepsis due to P. cepacia in a child with no known defect in immune system. Virulence of the organism was indicated by the high magnitude of septicaemia. The organism was successfully eliminated by ceftriaxone but the patient died of renal failure.

Bacteremia↗

The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture.

In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put (N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4-butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect. In a first step (1-48 h after treatment), cells exposed to these compounds show large intracellular vacuoles. We failed to detect any acid phosphatase activity in these intracellular structures revealing that they were not lysosomes. Electron microscopy observations argue for the conclusion that these vacuoles are an hypertrophy of the endoplasmic reticulum (ER) and/or of the Golgi vesicles. Our hypothesis is that this typical effect of the analogs reveals that ER could be a physiological target of endogenous polyamines. At a later stage (6 days after treatment), the cells undergo morphological and biochemical changes: thin and long expansions characterize the cells and the GFA protein is overexpressed. Correlated to both these effects, karyotypic modifications are found in chromosomes 3 and 6. These changes evoke a differentiation of the treated cells. The work provides evidence that N-methylated polyamine analogs taking the place of endogenous putrescine demonstrate a hopeful antitumor effect.

Cell Differentiation↗

Calcium ionophores inhibit the release of endothelin-1 from endothelial cells.

We have determined the effect on endothelin-1 (ET-1) release of stimulating cultured endothelial cells for 24 h with Ca2+ ionophores. The results obtained using cultured bovine aortic endothelial cells (BAECs) were compared with those using the human endothelial cell line (EA.hy 926). ET-1 was measured using a radioimmunoassay specific for the C-terminal ET[16-21] sequence. Ionomycin (1 microM) lessened ET-1 accumulation over 24 h in the conditioned medium from BAECs (-37%) and EA.hy 926 (-25%). A23187 was a more potent inhibitor of ET-1 release. With BAECs, ET-1 release was inhibited by 28% and 77% at 0.1 microM and 1 microM A23187, respectively. The corresponding decreases for EA.hy 926 were 20% and 98%. A23187 at 0.2 microM lowered ET-1 concentrations in the medium after 24 h by 44% and 24% for BAECs and EA.hy 926, respectively. Neither NG-monomethyl-L-arginine (0.2 mM) nor indomethacin (10 microM), either alone or in combination, affected the inhibition by A23187. Thus, this inhibitory effect is not dependent on the stimulation of nitric oxide or prostacyclin synthesis. Additional factors in endothelial cells, activated by elevated Ca2+ levels, may be important in exerting an inhibitory influence on ET-1 formation.

Animals↗

Effects of phosphoramidon in endothelial cell cultures on the endogenous synthesis of endothelin-1 and on conversion of exogenous big endothelin-1 to endothelin-1.

Several studies have shown that phosphoramidon (PHOS) reduces the release of endothelin-1 (ET-1) from cultured endothelial cells. Moreover, the main endothelin-converting enzyme (ECE) activity in these cells is a membrane-bound metallopeptidase that is also inhibited by PHOS. We have investigated further the role of the PHOS-sensitive ECE in the conversion of big ET-1 to ET-1. ET-1 was measured using a radioimmunoassay specific for the C-terminal ET[16-21] sequence. The effect of PHOS on the production of ET-1 from endogenous precursors was determined using cultured bovine aortic endothelial cells (BAECs) and the human endothelial cell line (EA.hy 926). The concentrations of ET-1 accumulating in the medium over 24 h from BAECs were lowered by PHOS (-27% 10 microM, -76% 100 microM). In contrast, with EA.hy 926 cells, the same concentrations of PHOS increased by five- to sixfold the amount of ET-1 present in the medium after 24-h incubation. In other experiments, incubation of big ET-1 (1 microM) with intact BAECs or EA.hy 926 cells resulted in the generation of ET-1, and with both cell types this was inhibited by PHOS (IC50: BAECs = 6.4 microM; EA.hy 926 = 0.26 microM). These results are consistent with both cell types having a PHOS-sensitive ECE that is readily accessible to exogenous big ET-1 and is therefore probably located on the plasma membrane. Furthermore, another intracellular ECE may play a part in the endogenous intracellular formation of ET-1 in EA.hy 926 cells.

Amino Acid Sequence↗