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Biomedical subjects

N Khan

Publications and source records attributed to N Khan.

At least 73 records · Page 4Linked to original sources

Effects of kaliuretic peptide on sodium and water excretion in persons with congestive heart failure.

Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four- to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 212 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5- and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two- to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention.

Adult↗

A convergent strategy for the synthesis of beta-carba-galacto-disaccharides.

[reaction in text] A convergent strategy for the synthesis of beta-carba-galacto-disaccharides is illustrated by the preparation of 1 and 4, from a central "glycone" component 22, and the corresponding "aglycone" segments, monosaccharide alcohols, 23a or 23b. The key step is the formation of the carbasugar ring via an oxocarbenium ion-enol ether cyclization.

Cyclization↗

Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia.

Cytoarchitectural abnormalities have been reported in the cortex in schizophrenia. These suggest a developmental origin for this disorder. The Wnt signalling pathway is involved in the regulation of brain development; disruption of this pathway may lead to abnormal cortical development. In this study levels of three components of the Wnt signalling pathway; glycogen synthase kinase-3beta(GSK-3beta), beta-catenin and dishevelled-2 (Dvl-2) were determined in the prefrontal cortex of ten schizophrenic and ten control individuals using immunoblotting. GSK-3beta levels were significantly reduced in the schizophrenic group, while levels of beta-catenin and Dvl-2 did not differ between groups. This provides further evidence for an abnormality of the Wnt signalling pathway in schizophrenia.

Adaptor Proteins, Signal Transducing↗

Severe arterial occlusive disorder and brachysyndactyly in a boy: a further case of Grange syndrome?

We report on a 15-year-old boy with stenosis and occlusion of multiple cranial, renal, and celiac arteries, aneurysm of the basilar artery, bilateral cutaneous syndactyly between fingers IV-V, partial cutaneous syndactyly between fingers III-IV on the right hand, brachydactyly, and borderline mental retardation. The clinical course was characterized by recurrent abdominal pain, gastritis, and high blood pressure. The pattern of the clinical and radiological findings is different from fibromuscular dysplasia (FMD) and Moyamoya disease, and highly suggestive of a syndrome described by Grange in four siblings (MIM#602531) Grange et al. [1998: Am J Med Genet 75: 469-480].

Abnormalities, Multiple↗

Patterns of alcohol use and misuse among elderly rest home residents in Christchurch.

AIMS: To determine the prevalence of alcohol use and misuse among elderly rest home residents in Christchurch. METHODS: A cross-sectional prevalence survey was conducted among 175 residents aged 65 years and over, randomly selected from 30 rest homes in Christchurch, in 1998. Hazardous patterns of alcohol consumption in the past twelve months were determined by the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and alcohol dependence in the past 12-months and lifetime was determined by a strctured clinical interview using DSM-IV criteria. RESULTS: Of 246 eligible participants, 175 (71.1%) residents were interviewed, 115 women and 60 men, mean age, 82.6 years (SD=7.8) compared with 83.2 years (SD=6.3) for non-participants. The prevalence of hazardous patterns of alcohol consumption in the past twelve months by the AUDIT (cut-off score 8) was 5.1% (95% CI = 1.8-8.4). According to DSM-IV criteria, the prevalence of lifetime alcohol dependence was 20.5% (95% CI = 13.5-27.6) and for the past twelve months was 0.5% (95% CI = 0-1.7). The prevalence of lifetime alcohol dependence was significantly higher in men 36.7% (95% CI = 23.2-50.1) than women 12.2% (95% CI = 5.6-18.8) (p = 0.0001). CONCLUSIONS: In spite of advanced age, a small proportion of elderly rest home residents consumed quantities of alcohol that put them at risk of future damage to physical or mental health. Lifetime prevalence of alcohol dependence was comparable to the general population estimates and was higher in men than women.

Aged↗

Inhibition of depolarisation-evoked [(3)H]noradrenaline release from SH-SYFY human neuroblastoma cells by muscarinic (M1) receptors is not mediated by changes in [Ca(2+)].

The aim of this study was to obtain further understanding of the mechanism by which activation of muscarinic M(1) receptors inhibits K(+)-evoked noradrenaline (NA) release in the human neuroblastoma SH-SY5Y. Previous studies have found that muscarinic M(1) and M(3) receptors couple to the activation of phospholipase C in SH-SY5Y cells leading to an increase in (a) intracellular calcium ([Ca(2+)](i)) and (b) activation of protein kinase C (PKC). This study used specific inhibitors of PKC and conditions which deplete Ca(2+)(i) stores to examine the role of protein kinase C and changes in [Ca(2+)](i) in mediating the inhibition of K(+)-evoked NA release by muscarine. Our data show that pretreatment of SH-SY5Y cell layers with bisindolylmaleimide I (BIM-I) (i) failed to reverse inhibition of K(+)-evoked NA release by muscarine but (ii) did overcome the attenuation of muscarine inhibition following pretreatment with TPA. Furthermore pretreating cell layers with Ca(2+)-free Hepes buffered saline in the presence of thapsigargin, conditions which prevented muscarine induced increases in [Ca(2+)](i), failed to prevent inhibition of K(+)-evoked NA release by muscarine. The effect of muscarine on K(+)-evoked uptake of Ca(2+)(e) was examined in SH-SY5Y cells loaded with Fura-2. Muscarine inhibited Ca(2+)(e)-uptake by decreasing the rate at which Ca(2+) entered SH-SY5Y cells via voltage sensitive Ca(2+)-channels. Thus this study shows that muscarine inhibits depolarisation-evoked NA release by a mechanism which is not dependent on activation of PKC or release of Ca(2+) from internal stores.

Calcium↗

Transmyocardial laser revascularization: is the enthusiasm justified?

BACKGROUND: Transmyocardial laser revascularization (TMLR) is advocated to offer relief of incapacitating angina for patients whose coronary vessels are poor targets for coronary artery bypass graft surgery (CABG) or balloon angioplasty and stenting. In spite of significant mortality and morbidity, the preliminary reports from centers performing the procedure were quite enthusiastic for a period of about 1 year following the procedure. HYPOTHESIS: The study aimed to determine mortality, morbidity, and long-term results of TMLR. METHODS: The study included 19 individuals with incapacitating angina not suitable for CABG or percutaneous balloon angioplasty. Patients were followed up clinically for death, myocardial infarction, heart failure, arrhythmia, and repeated hospital admissions for unstable angina or other conditions. Stress testing with radionuclide tracers was done following surgery in patients who were not unstable. RESULTS: Of 19 patients, 8 experienced significant morbidity. There was one hospital death. Four died within 17 months. Relief from angina of two classes or more was present in 15 of 18 patients (83.3%) for a variable time period. Mean time for anginal relief was 8.0 months (range 1-30 months). At last follow-up, only two patients with a hybrid procedure (both CABG and TMLR in the same sitting) had mild angina for 17 and 29 months, respectively. All others with a mean follow-up period of 21.2 months (range 6-53 months) developed unstable angina or had a large area of ischemia on stress radionuclide studies. Despite a high incidence of significant angina in patients after TMLR, hospitalization was reduced from an average of 42.6 days pre procedure in the year before to 21 days during the follow-up period post procedure. CONCLUSION: Transmyocardial laser revascularization is associated with significant relief of angina pectoris in the majority of patients with severe diffuse coronary artery disease; however, this relief is short-lived in most. When mortality and morbidity are factored in, TMLR cannot be enthusiastically recommended.

Aged↗

Prevalence of ocular injuries, conjunctivitis and use of eye protection among dental personnel in Riyadh, Saudi Arabia.

AIMS: To find out the prevalence of ocular injury and infection among dental personnel in Riyadh, Saudi Arabia. PARTICIPANTS: Two hundred and four dental personnel. METHOD: A questionnaire completed by researchers and observation during practice. RESULTS: The response rate was 81%. Dentists and dental technicians had a similar prevalence (42.3%) of foreign bodies in their eyes during the period of one month. Almost 50.5% of dentists rarely had foreign bodies in their eyes, while only 22.2% of dental technicians claimed the same. The majority of dental surgery assistants (73.6%) never experienced foreign bodies in their eyes. Only 27.0% of female personnel had foreign bodies in their eyes as compared to 73.0% of male personnel, while only 28.5% of females had conjunctivitis as compared to 71.4% among male personnel. 75% of regular eye protector wearers (EPW) never had foreign bodies while 67.2% EPW never had conjunctivitis. Dental technicians were more prone to ocular injury, 13.8% as compared to 4.4% of dentists. Only 30% of the regular eye protector wearers suffered ocular injury. CONCLUSIONS: Protection of the eyes should be emphasised and practised at undergraduate level. The awareness of eye protection should be highlighted at all clinical and research symposia. Further studies should be conducted to assess the financial implications of ocular injuries and infections in dental institutions and practices. Recommendations are made for universal precautions and the observation of safety at work guidelines by all dental team members.

Conjunctivitis↗

Altered connexin expression in human congestive heart failure.

Congestive heart failure is associated with a high risk of life-threatening ventricular re-entrant arrhythmias. Down-regulation of the principal gap-junctional protein of the ventricular myocytes, connexin43, has previously been implicated in arrhythmia in ischaemic heart disease, but it is not known whether connexin43 is similarly reduced in heart failure due to idiopathic dilated cardiomyopathy, whether disease-related connexin43 down-regulation occurs at the level of transcription or translation, or whether the expression of other connexin isotypes is altered in congestive heart failure. We therefore investigated the expression of the four connexins expressed in the heart-connexins 43, 40, 45 and 37-at the mRNA and protein levels in explanted hearts from transplant patients with end-stage heart failure (NYHA class 4) by immunoconfocal analysis, and northern and western blotting. Connexin43 mRNA and protein were markedly downregulated in the left ventricle in end-stage heart failure due both to ischaemic cardiomyopathy and idiopathic dilated cardiomyopathy. Connexin43 content was spatially heterogeneous in the diseased ventricle. Connexin40 mRNA was increased in the ischaemic group, more so in the left ventricle than the right. This correlated with an increased depth of connexin40 protein expression in myocytes at the endocardial surface. Connexin45 mRNA and protein, present only in very low quantities, followed a similar trend to connexin43, while connexin37 (exclusively expressed in endothelium) showed no change. Our findings show that congestive heart failure is associated with significantly reduced levels of the principal gap junction protein, connexin43, in the left ventricle, potentially contributing to enhanced arrhythmogenicity and contractile dysfunction. This down-regulation is due predominantly to a reduced transcript steady-state level. Elevated connexin40 may represent a compensatory response that improves the spread of depolarization in the otherwise compromised ischaemic ventricle.

Adult↗

A basic study on lesion detectability for hot spot imaging of positron emitters with dedicated PET and positron coincidence gamma camera.

The aim of this study was to explore the correlations of detectability and the semi-quantification for hot spot imaging with positron emitters in positron emission tomography (PET) and with a positron coincidence detection system (PCD). Phantom study results for the measurement of the lesion-to-background (L/B) ratio ranged from 2.0 to 30.3, and detectability for hot spot lesion of PET and PCD were performed to correspond to clinical conditions. The detectability and semi-quantitative evaluation of hot spots from 4.4 mm to 36.9 mm in diameter were performed from the PET and PCD images. There were strong correlations between the L/B ratios derived from PET and PCD hot spot images and actual L/B ratios; but the L/B ratio derived from PET was higher than that from PCD with a significant difference of 10% to 54.8%. The detectability of hot spot imaging of PCD was lower than that of PET at 64.8% (PCD) versus 77.8% (PET). Even the actual L/B ratio was 8.0, hot spots more than 10.6 mm in diameter could be clearly identified with PCD imaging. The same identification could be achieved with PET imaging even when the actual L/B ratio was 4.0. This detailed investigation indicated that FDG PCD yielded results comparable to FDG PET on visual analysis and semi-quantitative analysis in detecting hot spots in phantoms, but semi-quantitative analysis of the L/B ratio with FDG PCD was inferior to that with FDG PET and the detectability of PCD in smaller hot spots was significantly poor.

Gamma Cameras↗

The prevalence and pattern of nursing caries in Saudi preschool children.

OBJECTIVES: To determine the prevalence and pattern of nursing caries in Saudi preschool children of Riyadh area. DESIGN: Cross-sectional. SUBJECTS AND METHODS: A list of kindergartens was derived through random selection of one kindergarten from every area of Riyadh. A sample of 1,016 children with primary dentition only was examined for dental caries. The criterion used for nursing caries was presence of caries on the labial or lingual surfaces of at least two maxillary incisors with absence of caries in mandibular incisors. RESULTS: Two hundred and seventy-seven (27.3%) children were diagnosed as having nursing caries. The mean dmft of nursing caries children was 8.6 (+/- 3.4), with dt component of 7.6 (+/- 3.5), mt of 0 4 (+/- 0.9) and ft of 0.6 (+/- 1.7). The older children had significantly higher mean dmft as compared with younger children. The teeth most affected by caries were maxillary central incisors (93.9%), whereas the least affected were mandibular canines (9.6%). A great majority of children (95.7%) had caries in both anterior and posterior teeth. The probability of bilateral molar caries was very high in nursing caries children; highest (94.7%) in mandibular first molars. CONCLUSIONS: The caries prevalence was high in the study population. The maxillary central incisors were most affected by caries. The probability of bilateral molar caries was very high.

Bottle Feeding↗

Purification of cytomegalovirus-specific CD8 T cells from peripheral blood using HLA-peptide tetramers.

Cytomegalovirus (CMV) reactivation and disease remains an important clinical problem for patients after allogeneic stem cell transplantation. Impaired cellular immune control of viral replication is responsible for viral reactivation, and transfer of CMV-specific T cells from transplant donors can be effective in providing protection. Recent reports have indicated that the frequency of CMV-specific CD8(+) T cells in the peripheral blood of healthy donors is surprisingly high. Here we demonstrate that by using a combination of human leucocyte antigen (HLA) Class I-peptide tetramers and magnetic selection it is possible to select CMV-specific T cells from CMV antibody-positive individuals to high purity. Reliable purification of CMV-specific T cells up to 99.8% of CD8(+) cells was possible within hours, even when starting with a precursor frequency of < 0.1% of peripheral blood CD8(+) T cells. CMV-specific T cells remained functional after the selection process. This novel form of antigen-specific T-cell selection should facilitate the selection of T cells for cellular immunotherapy to treat or prevent CMV disease after transplantation. In addition, this technique could potentially be applied to many antigens including against other infective agents and tumour-specific antigens.

Adoptive Transfer↗

Bedside external ventricular drain placement for the treatment of acute hydrocephalus.

The purpose of this retrospective study was to evaluate the results of external ventricular drain (EVD) placement for the management of hydrocephalus. We present our experience with 103 consecutive cases over one year, 56 of which had subarachnoid hemorrhage (SAH). Short tunnel ventriculostomy was performed at the bedside in the neurosurgical intensive care unit (NSICU), using sterile technique. Long-term care included meticulous site care by a dedicated NSICU nurse, daily cultures and prophylactic antibiotics. The average duration of EVD was 10.7 days (range 1-28 days). There was one case of positive cerebrospinal fluid (CSF) culture. Additional complications included one small intraparenchymal hematoma and two cases of EVD disconnection. No patient died form EVD-associated complications. No rebleed from aneurysmal SAH was seen. There was no correlation between the duration of EVD and infection. We conclude that placement of short EVD in the NSICU is safe and can be maintained for the required duration of treatment with minimum infection rate.

Acute Disease↗

Identification of a nonmucin glycoprotein (gp-340) from a purified respiratory mucin preparation: evidence for an association involving the MUC5B mucin.

Rate-zonal centrifugation of a reduced and alkylated respiratory mucin preparation identified a protein-rich fraction. This was subjected to trypsin treatment and one of the many liberated peptides was purified and its N-terminal sequence determined. The peptide was identical to a 14 amino acid sequence from the scavenger receptor cysteine-rich domain containing glycoprotein gp-340. A polyclonal antiserum, raised against the peptide, stained the serous cells in the submucosal glands of human tracheal tissue. The glycoprotein was purified from respiratory mucus by density-gradient centrifugation, gel chromatography, and anion exchange chromatography. The molecule exhibited a heterogeneous distribution of buoyant density (1.28-1.46 g/ml) that overlapped with the gel-forming mucins, was included on Sepharose CL-2B and was quite highly anionic. SDS-PAGE indicated a mass greater than 208 kDa and measurements performed across the molecular size distribution indicated an average M(r) of 5 x 10(5) with a range of M(r) from 2 x 10(5) to 1 x 10(6). Gel chromatography of respiratory mucus extracts ("associative" and "dissociative") indicated that this glycoprotein forms complexes that may involve the large gel-forming mucins MUC5AC and MUC5B. Rate zonal centrifugation suggested such complexes are more likely to involve MUC5B rather than MUC5AC mucins.

Amino Acid Sequence↗

Overexposure analysis of pulsed distributed feedback laser source.

The goal of this study is to assess the risk of overexposure, when DFB dye laser is used for medical treatment in pulsed mode operation. Results of experimental study showing an unexpected rise of energy in pulses of distributed feedback dye laser (DFDL) output due to temperature phase gratings in dye cell during passively Q switched and mode-locked operation is reported. This unintended increase in the number of pulses, pulse duration, per pulse energy may cause side effects, when used for selective photothermolysis. To probe this phenomenon the most commonly used Rh6G dye was excited with 10-20 pulses of second harmonic of a passively Q switched and mode-locked Nd:yttrium-aluminum-garnet(YAG) laser. The outputs of DFDL and Nd:YAG laser were recorded by an Imacon-675 streak camera. The peak of DFDL output pulses was found delayed proportionally from the peak of the Nd:YAG pulses by more than an interpulse period of excitation laser. A computer program was used to simulate the experimentally measured results to estimate the thermal decay constants and energy retained by medium. The delay between peaks of Nd:YAG (input) and DFDL (output) pulses was found to vary from 10 to 14 ns for various cavity lengths. It was interesting to note that for smaller inter-pulse periods the effect of gradual gain buildup satisfied the threshold conditions for some of the pulses that otherwise cannot lase. This may lead to unintended increase in energy fluence causing overexposure-induced bio effects.

Feedback↗

Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women.

The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRbeta-dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater in placentae from HIV-1-infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.

Adult↗