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Biomedical subjects

S Akhtar

Publications and source records attributed to S Akhtar.

At least 73 records · Page 4Linked to original sources

Use of active noise cancellation devices in caregivers in the intensive care unit.

OBJECTIVE: Recent development of noise cancellation devices may offer relief from noise in the intensive care unit environment. This study was conducted to evaluate the effect of noise cancellation devices on subjective hearing assessment by caregivers in the intensive care units. DESIGN: Randomized, double-blind. SETTING: Adult medical intensive care unit and pediatric intensive care unit of a teaching hospital. SUBJECTS: Caregivers of patients, including nurses, parents, respiratory therapists, and nursing assistants from a medical intensive care unit and pediatric intensive care, were enrolled in the study. INTERVENTION: Each participant was asked to wear the headphones, functional or nonfunctional noise cancellation devices, for a minimum of 30 mins. MEASUREMENTS: Subjective ambient noise level was assessed on a 10-point visual analog scale (VAS) before and during headphone use by each participant. Headphone comfort and the preference of the caregiver to wear the headphone were also evaluated on a 10-point VAS. Simultaneously, objective measurement of noise was done with a sound level meter using the decibel-A scale and at each of nine octave bands at each bedspace. RESULTS: The functional headphones significantly reduced the subjective assessment of noise by 2 (out of 10) VAS points (p < 0.05) in environments of equal objective noise profiles, based on decibel-A and octave band assessments. CONCLUSION: Noise cancellation devices improve subjective assessment of noise in caretakers. The benefit of these devices on hearing loss needs further evaluation in caregivers and critically ill patients.

Adult↗

Inhibition of coronary thrombosis and local inflammation by a noncarbohydrate selectin inhibitor.

We tested the hypothesis that selectin inhibition with blocking antibodies or a small-molecular-weight inhibitor of L-, P-, and E-selectin, methoxybenzoylpropionic acid (MBPA), prevents thrombus formation in a canine coronary Folts' model. Cyclic flow variations (CFVs) were induced by crush injury and constriction of the left anterior descending coronary artery in dogs. Systemic infusion of antibodies to P- and L-selectin abolished CFVs, respectively, in 50% and 17% of treated dogs [P = not significant (NS)]. The combination of P- and L-selectin antibodies suppressed CFVs in 60% of treated dogs (P = NS). In contrast, systemic selectin blockade by intravenous infusion or local adventitial application of MBPA markedly reduced CFVs and, in addition, reduced myocardial myeloperoxidase (MPO) activity. We conclude that inhibition of L-, P-, and E-selectin binding by a small-molecular-weight, noncarbohydrate compound markedly reduces arterial thrombosis, whereas systemic administration of antibodies to L- and P-selectin fail to reproduce this antithrombotic effect. These results underscore the role of selectins in the pathogenesis of arterial thrombosis under high shear stress and suggest that inhibition of P- and L- selectin may not suffice to prevent thrombus formation in this model. The role of E-selectin in thrombus formation in this model awaits further testing.

Animals↗

Causes and consequences of duration of untreated psychosis in schizophrenia.

BACKGROUND: It is unclear what determines duration of untreated psychosis (DUP) in schizophrenia and why long DUP predicts poor outcome. AIMS: First, to test the hypothesis that specific patterns of symptoms and social functioning acting before treatment prolong DUP. Second, to clarify the mechanisms linking DUP with recovery after treatment. METHOD: Two hundred and forty-eight consecutive first admissions with schizophrenia were interviewed to assess DUP, symptoms and social functioning at admission, and symptoms were re-assessed after 6-12 weeks. RESULTS: Median DUP was 12 weeks. Long DUP was predicted by poor insight, social isolation and preserved coping skills, but not by demographic factors. Even allowing for all these variables, long DUP predicted poor outcome. CONCLUSIONS: Longer DUP results partly from a pattern of symptoms and social functioning which reduces concern by the sufferer and relevant others. DUP's relationship to outcome is strongest in the initial months of psychosis. This has implications for targeting early intervention.

Adolescent↗

The management of dysphasia in skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH), or Forestier's disease, is an ossifying condition frequently encountered in otolaryngology as it affects 12-28 per cent of the adult population. This form of hyperostosis can manifest clinically with dysphagia, food impaction, hoarseness, stridor, myelopathies and other neurological problems. Judicious management of severe dysphagia proves challenging. The failure of conservative care often leaves surgery as the only option. In this report an anterolateral transcervical surgical approach to the confluent osteophytes is discussed and the value of videofluoroscopic swallow highlighted.

Aged↗

Mental pain and the cultural ointment of poetry.

The author argues that mental pain consists of a wordless sense of self-rupture, longing and psychic helplessness that is vague and difficult to convey to others. It usually follows the loss of a significant object or its abrupt refusal to meet one's anaclitic needs. This results in the laceration of an unconscious, fused self-object core of the self. Abruptly precipitated discrepancies between the actual and wished-for self-states add to the genesis of mental pain. Issues of hatred, guilt, moral masochism as well as fantasies of being beaten can also be folded into the experience of mental pain. The feeling is highly disturbing and is warded off by psychic retreat, manic defence, induction of pain into others and changing the form and function of pain. Each of these can have a pathological or healthy outcome depending upon the intrapsychic and social context and upon whether they ultimately permit mourning to take place or not. Poetry serves to render mental pain bearable by enhancing empathy with one's own repudiated parts. With the help of two clinical vignettes, the multi-faceted (defensive, formal and content-based) role of poetry in reducing mental pain, enhancing mentalisation of its sources and facilitating mourning is discussed. It is suggested that through poetry, culture and affect meet and, in this encounter, both are enriched.

Affect↗

Influences of cultural origin and sex on work values.

This study examined the influences of cultural origin and sex on intrinsic, instrumental, and systemic work values using an individual level analysis. Data on importance of work outcomes were obtained from a stratified sample of 111 Hong Kong Chinese, British, and American managerial employees of a multinational media company. Analysis of variance showed that compared to Hong Kong Chinese, British and American managerial employees scored significantly higher on intrinsic work values and lower on instrumental work values. Cultural origin did not significantly influence systemic work values. Sex differences in the three work values were also not significant. Implications for managerial practice are discussed.

Cross-Cultural Comparison↗

Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain.

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h with little or no ODN remaining in the neostriatum after 48 h. In comparison, fluorescently-labelled ODNs delivered using polymer microspheres were intensely visible in cells after 48 h post-administration and the fluorescence appeared to be diffuse covering both cytosolic and nuclear regions. Dual-label immunohistochemical analyses suggested that ODNs were mainly distributed to neuronal cells. These data indicate that site-specific administration of ODNs using biodegradable polymer microspheres will not only provide sustained delivery of nucleic acids but can also improve the cellular distribution of ODNs to brain cells. Sustained or controlled-release biodegradable polymer formulations, therefore, represent an attractive strategy for improved local delivery of ODNs to the CNS.

Animals↗

Studies on uptake, sub-cellular trafficking and efflux of antisense oligodeoxynucleotides in glioma cells using self-assembling cationic lipoplexes as delivery systems.

The cellular uptake of antisense oligodeoxynucleotides (ODNs) may be enhanced by the use of carriers such as cationic liposomes or lipoplexes, but little is known about the intracellular fate and subcellular trafficking of these systems in target cells. In this study, we report on the cellular uptake and biodistribution of ODNs in the presence and absence of optimised self-assembled cationic lipoplexes using the C6 glioma cell line as an in vitro model. Biotin or radiolabelled 15-mer phosphorothioate (PS) ODNs were synthesised and their cellular uptake and subcellular biodistribution characterised in the presence and absence of an optimised cationic lipoplex delivery system using studies ranging from cellular association, cellular efflux and transmission electron microscopy (TEM). Ultrastructural studies clearly showed PS ODNs in the absence of liposomal delivery to be sequestered within endosomal and lysosomal vesicular bodies indicative of endocytic uptake. ODNs were also visible, to a lesser extent, in the nucleus and cytoplasm. By employing DOSPA (2'-(1",2"-dioleoyloxypropyldimethyl-ammonium bromide)-N-ethyl-6-amidospermine tetra trifluoroacetic acid) and DOPE (dioleoylphosphatidylethanolamine) complex in a 3 : 1 ratio, as a delivery system for ODNs at a optimal lipid/DNA charge ratio of 1 : 1, the level of ODN cellular association was significantly increased by approximately 10-12 fold with a concomitant change in subcellular distribution of PS ODN. TEM studies indicated enhanced penetration of ODN within the cytosol and the cell nucleus with reduced presence in vesicular compartments. Efflux studies confirmed that cationic lipoplexes promoted entry of ODNs into 'deeper' cellular compartments, consistent with endosomal release. Optimised cationic lipoplexes improved cellular delivery of ODNs by enhancing cell association, uptake and by favourably modulating the intracellular trafficking and distribution of ODNs into non-vesicular compartments including the cytosol and nucleus.

Animals↗

Multivariate analysis of risk factors associated with genital ulcer disease among incarcerated males in Sindh.

OBJECTIVE: To evaluate the potential risk behaviors associated with the lifetime risk of self reported genital ulcer disease (GUD) among prison inmates. SETTING: Prison inmates from 14 prisons of Sindh Province. METHODS: A cross-sectional study was conducted on 3395 prison inmates during July to December, 1994. A questionnaire was used to assess the lifetime risk of self-reported GUD (whether or not the subject was ever affected with GUD up to present age) and to investigate demographic markers and risk behaviors for their possible association with lifetime risk of GUD using logistic regression analysis. RESULTS: The reported lifetime risk of GUD in the study sample was 11.4% (386/3395). In final multivariate logistic regression model the sexual behaviors which were independently associated with GUD were having sexual intercourse with female (adjusted OR = 1.7; 95% CI: 1.3-2.3, P = 0.0002), sexual intercourse with a prostitute (adjusted OR = 1.5; 95% CI: 1.2-2.0, P = 0.0008), sexual intercourse with man (adjusted OR = 2.2; 95% CI: 1.7-2.7, P = < 0.001) and sexual intercourse with man during current incarceration (adjusted OR = 1.9; 95% CI: 1.2-2.9, P = 0.0071). CONCLUSION: Health education needs to re-enforce monogamous relationship for high risk groups such as in our study. Although infrequent condom use was not a risk factor for GUD in this study, yet based on the results of previous studies, promotion of condom use should be the component of health education program.

Adolescent↗

Ultrastructural and molecular analysis of Bowman's layer corneal dystrophies: an epithelial origin?

PURPOSE: Two mutations (R555Q and R124L) in the BIGH3 gene have been described in anterior or Bowman's layer dystrophies (CDB). The clinical, molecular, and ultrastructural findings of five families with CDB was reviewed to determine whether there is a consistent genotype:phenotype correlation. METHODS: Keratoplasty tissue from each patient was examined by light and electron microscopy (LM and EM). DNA was obtained, and exons 4 and 12 of BIGH3 were analyzed by polymerase chain reaction and single-stranded conformation polymorphism/heteroduplex analysis. Abnormally migrating products were analyzed by direct sequencing. RESULTS: In two families with type I CDB (CDBI), the R124L mutation was defined. There were light and ultrastructural features of superficial granular dystrophy and atypical banding of the "rod-shaped bodies" ultrastructurally. Patients from three families with "honeycomb" dystrophy were found to carry the R555Q mutation and had characteristic features of Bowman's dystrophy type II (CDBII). CONCLUSIONS: There is a strong genotype:phenotype correlation among CBDI (R124L) and CDBII (R555Q). LM and EM findings suggest that epithelial abnormalities may underlie the pathology of both conditions. The findings clarify the confusion over classification of the Bowman's layer dystrophies.

Adult↗

Prevalence of plasmodium slide positivity among the children treated for malaria, Jhangara, Sindh.

OBJECTIVE: The aim of the study was to estimate the prevalence of malaria amongst the children with fever or history of fever. SETTING: Rural Health Centre (RHC), Jhangara, a town near the Manchhar Lake in Taluka Sehwan, District Dadu, Sindh. SUBJECTS: Four hundred and thirty eight children of 6 months to 10 years of age, who attended above described RHC during August through October 1997. METHODS: A Sindhi-translated standard questionnaire was used to record symptoms and duration of child's illness. Each child was physically examined, had their axillary temperature measured; and blood samples were collected from which Giemsa stained thick and thin blood films were examined for presence of Plasmodium parasites. RESULTS: The median age of the studied children was 24 months and 57% (250/438) were boys. Fifty three percent (231) of the study subjects were from Jhangara Town, 40% (177) and 7% (30) came from other villages and villages near to the Manchhar Lake respectively. The prevalence of Plasmodium slide positivity was 5.9% (26/438). Among Plasmodium slide positive children, 65% (17/26) were positive for P. falciparum and 35% (9/26) for P. vivax. Among the P. falciparum positive children, 88% (15/26) had scanty (MP, 1-10/100 fields) and 12% (2/26) had moderate density (MP, 10-100/100 fields) of infection. Seventeen percent (6/30) of the children from villages close to Manchhar Lake were Plasmodium slide positive compared to 7% (17/53) and 3% (5/177) from Jhangara town and other villages respectively. Cough, diarrhea, abdominal distention and vomiting were the commonly reported symptoms among the children of all ages at the time of interview. Guardians reported fever as part of the illness in all children, although during physical examination only 128 (29%) had axillary temperature > or = 37.5 degrees C. Pallor as an indicator for anemia, rash and prickly heat were the major recorded observations. CONCLUSION: The Prevalence of Plasmodium positivity was higher in children who attended from villages close to Manchhar lake, therefore especial measure needs to be considered for this area. In addition, the health care workers in rural Sindh need to adopt appropriate guidelines to differentiate the clinical malarial patients from patients with other potential infectious diseases, which may need other treatment.

Animals↗

Prevalence of obesity in adults--an epidemiological study from Kashmir Valley of Indian Subcontinent.

OBJECTIVE: Obesity is a health problem in the majority of the developed countries and is emerging as a serious problem in the developing countries. In this study we examined 5083 Kashmiri adults to determine the prevalence of obesity. METHODS: In this epidemiological study, after multistage sampling procedure from all the six districts of Kashmir Valley, 5083 Kashmiri adults (males and non-pregnant females of > or = 40 years age) were examined for body mass index (BMI) and waist to hip ratio (WHR). RESULTS: Out of 5083 study subjects, 2496 were males and 2587 were females. BMI ranged between 14.6 to 38.5 kg/m2 in males and between 13.6 to 42.6 kg/m2 in females. BMI in females was comparatively more than that in males (23.88 +/- 3.94 Vs 22.30 +/- 3.11, p < 0.001). WHR ranged between 0.68 to 1.16 in males and between 0.65 to 1.16 in females. Again females had comparatively more WHR than their male counterparts (0.935 +/- 0.055 vs 0.926 +/- 0.055, P < 0.001). According to BMI, the overall prevalence of obesity in the study population was 15.01%; the prevalence of obesity in males was 7.01% and in females 23.69%. CONCLUSIONS: We conclude that obesity is a growing problem even in developing regions like ours. It is more common in females and in urban population.

Adult↗

A study on fatty acid composition of fish oil from two marine fish, Eusphyra blochii and Carcharhinus bleekeri.

Two species of marine fish found in coastal waters of Karachi (Pakistan) were studied, Eusphyra blochii (Hammer-headed Shark) and Carcharhinus bleekeri (Shark) for their fatty acid composition. The isolation, identification and characterization of these fatty acids were carried out by gas liquid chromatography (GLC) and a combination of TLC-GLC technique. A large variation was observed between hammer-headed shark liver oil and shark liver oil. Twenty five individual fatty acids from the oil of marine fish were analyzed among those the palmitic acid was a major saturated fatty acid while stearic acid was the other major constituent. Among unsaturated fatty acids monoenoic e.g. oleic and palmitoleic acids were the major constituents and traces of dienoic and trienoic fatty acids were also found. In addition medicinally important polyunsaturated fatty, acid eicosapentaenoic and docosahexaenoic acids were also identified.

Journal Article↗

Recreation of neuronal Kv1 channel oligomers by expression in mammalian cells using Semliki Forest virus.

The multiple roles of voltage-sensitive K(+) channels (Kv1 subfamily) in brain are served by subtypes containing pore-forming alpha (1.1-1.6) and auxiliary beta subunits, usually in an (alpha)(4)(beta)(4) stoichiometry. To facilitate structure/activity analysis, combinations that are prevalent in neurones and susceptible to alpha-dendrotoxin (alphaDTX) were reproduced in mammalian cells, using Semliki Forest virus. Infected Chinese hamster ovary cells expressed N-glycosylated Kv1.1 and 1.2 alpha subunits (M(r) approximately 60 and 62 K) that assembled and bound [(125)I]-alphaDTX with high affinity; an appreciable proportion appeared on the cell surface, with Kv1.2 showing a 5-fold enrichment in a plasma membrane fraction. To obtain 'native-like' alpha/beta complexes, beta1.1 or 2.1 (M(r) approximately 42 and 39 K, respectively) was co-expressed with Kv1.1 or 1.2. This slightly enhanced N-glycosylation and toxin binding, most notable with beta2. 1 and Kv1.2. Solubilization of membranes from cells infected with Kv. 1.2 and beta2.1, followed by Ni(2+) chromatography, gave a purified alpha1.2/beta2.1 complex with a size of approximately 405 K and S(20, W) = 15.8 S. Importantly, these values indicate that four alpha and beta subunits co-assembled as in neurones, a conclusion supported by the size ( approximately 260 K) of the homo-tetramer formed by Kv1.2 alone. Thus, an authentic K(+) channel octomer has been reconstructed; oligomeric species were also found in plasma membranes. To create 'authentic-like' hetero-oligomeric channels, Kv1.1 and 1.2 were co-expressed and shown to have assembled by the precipitation of both with IgGs specific for either. Consistently, confocal microscopy of cells labeled with these antibodies showed that the relatively low surface content of Kv1.1 was increased by Kv1.2. [(125)I]-alphaDTX binding to these complexes was antagonized by DTX(k), a probe selective for Kv1.1, in a manner that mimicks the pattern observed for the Kv1.1/1.2-containing channels in neuronal membranes.

Animals↗

A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum.

Voltage-gated K(+) channels (Kv1) are important in glia, being required for cell proliferation. Herein, reactive astrocytes from a rat cerebellar lesion were shown to contain Kv1.1, -1.2, -1.3, -1.4, and -1.6 alpha plus beta1.1 subunits, as well as an unusual beta2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta1.1 subunits. Reverse transcriptase-polymerase chain reaction revealed a novel product of the beta2 gene in C6 cells and reactive astrocytes, but not in cultured astrocytes or rat normal brain. Its cloning identified a variant, Kvbeta2.1A, alternatively spliced between I24 and Y39. Despite this 14 residue deletion, Kvbeta2.1A assembled cotranslationally with Kv1.1 or -1.2 and, when coexpressed with Kv1. 4 in oocytes, increased the inactivation rate of this K(+) current. Whereas the full-length beta2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of beta2.1A varied from a modest elevation of the current to a slight suppression in some cases. In summary, this is the first report of the existence of an alternatively spliced product of the Kvbeta2.1 gene in C6 cells and reactive astrocytes, and supports the involvement of its core region (residues 39 onward) in assembly with alpha subunits while excluding a contribution of the adjacent 14 residues to accelerating the inactivation of Kv1.4.

Alternative Splicing↗

Cellular delivery of hammerhead ribozymes conjugated to a transferrin receptor antibody.

Chemically-modified hammerhead ribozymes are sequence-specific RNA enzymes that can cleave target mRNA. These molecules have potential application as biological tools to understand gene expression and as therapeutic agents for the selective down-regulation of genes implicated in disease. However, as a result of their polyanionic character and relatively large molecular weights, ribozyme delivery to target cells is relatively inefficient. Using nuclease resistant 2'-O-methyl-modified ribozymes targeting the c-erbB1 oncogene, we have evaluated the potential use of human monoclonal transferrin-receptor antibody (TRA)-ribozyme conjugates for the improved delivery of ribozymes to A431 tumour cells. A 37-mer ribozyme derivatized with a free thiol-group at the 5'-end and bearing an internal [32P]-radiolabel was conjugated to either TRA or a non-specific IgG antibody using the heterobifunctional crosslinker, succinimidyl 4-(maleimido methyl)cyclohexane-1-carboxylate (SMCC). Up to six molecules of the ribozyme could be conjugated to one molecule of antibody. Cellular uptake studies in cultured human epidermoid A431 carcinoma cells showed that approximately a three-fold increase in cellular association could be obtained with the TRA-ribozyme conjugate compared to the free ribozyme. Cellular association of the conjugate was temperature-dependent and was inhibited by competition with excess free transferrin receptor antibody implying that conjugate uptake was consistent with the transferrin receptor-mediated endocytosis pathway. Treatment of cells with monensin further enhanced TRA-ribozyme conjugate cell association indicating that ribozyme delivery of conjugates may be further improved by strategies that modulate vesicular trafficking in cells.

Animals↗

Deposits and proteoglycan changes in primary and recurrent granular dystrophy of the cornea.

OBJECTIVE: To investigate the origin and distribution of granular deposits in the corneas of 3 patients with granular dystrophy, 1 of whom had previously received a lamellar keratoplasty in which the granular dystrophy had recurred. METHOD: Corneal tissue from 2 patients with primary granular dystrophy (patients 1 and 2) and from a patient with recurrent granular dystrophy (patient 3) was examined. Corneal graft tissue was fixed in (1) 3% glutaraldehyde in sodium cacodylate buffer, (2) 2.5.% glutaraldehyde in sodium acetate buffer containing cuprolinic blue, and (3) 4% paraformaldehyde in phosphate-buffered saline. RESULTS: In patient 1 (aged 48 years), electron-dense granular structures were observed in epithelium, Bowman layer, and throughout the stroma. Bowman layer was absent in several places. Patient 2 (aged 78 years) showed similar features except with more deposits in the stroma. In patient 3 (aged 48 years), granular structures were heavily deposited in the epithelium; there were also some deposits in the posterior (host) stroma, some of which were associated with partially degenerated keratocytes. Bowman layer appeared normal. In all 3 patients, the intracellular or extracellular granular structures were surrounded by fine fibrillar material and abnormal proteoglycans. Electron-lucent spaces within the corneal stroma contained large quantities of abnormal proteoglycan filaments that were attached in part to collagen fibrils. CONCLUSIONS: Results from patient 3 support an epithelial origin for the deposits, presumably from keratoepithelin, aggregated with other proteins. The role of keratocytes is less clear, although the presence of deposits in the stroma of all 3 patients, some associated with keratocytes, suggests that these cells might produce granular material in addition to abnormal proteoglycans.

Aged↗

Balloon rupture during stent implantation: A novel technique of salvage with a new manual power injector.

Pinhole leak or rupture of a stent delivery balloon is a well-recognized technical problem encountered in vascular interventions. This event leads to inadequate stent expansion. These stents cannot be fully deployed with the same balloon and frequently the balloon cannot be retrieved without dislodging the stent. We describe a technique for successful stent deployment in such situations using the Oz Power Syringe, a new manual power injector. Cathet. Cardiovasc. Intervent. 48:74-77, 1999.

Aged↗