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Biomedical subjects

N Hussain

Publications and source records attributed to N Hussain.

At least 19 recordsLinked to original sources
PubMed2003

Translation and cultural adaptation of health questionnaires.

BACKGROUND: Health research in Pakistan often requires questionnaires in English language developed in the West to be translated into the local language. Many of the factors measured by these questionnaires are complex and apply to a different culture. Simple translations may lead to problems of validity and reliability in the Pakistani setting. This paper describes the strategies adopted for the translation and cross-cultural adaptation of the Self-Reporting Questionnaire (SRQ), a screening questionnaire for mental health developed by the World Health Organisation. METHODS: A general protocol was developed for translation of questionnaires into Urdu, describing each step in the translation procedure. Key informant interviews were carried out to obtain better cultural understanding of difficult concepts. The translation was tested and disputed items discussed in a focus group in a structured manner. RESULTS: Modifications were made to the questionnaire in light of the target population's culture and language. CONCLUSION: Simple translations are often insufficient for complex questionnaires. Key informant interviews and focus groups are useful to address conceptual and construct issues in such questionnaires.

Cross-Cultural Comparison↗
PubMed2002

Muscarinic, adenosine A(2) and histamine H(3) receptor modulation of haloperidol-induced c-fos expression in the striatum and nucleus accumbens.

It is generally believed that haloperidol exerts its motor side effects and therapeutic effects mainly by antagonizing dopamine D(2) receptors in the striatum and the nucleus accumbens, respectively. Several neurotransmitters/modulators, including glutamate, acetylcholine, adenosine and histamine, affect dopaminergic activity in these centers. We have recently shown that N-methyl-D-aspartate receptor-mediated modulation of haloperidol-induced c-fos expression differs in functionally specific regions of the striatum and the nucleus accumbens. In the present study, the entire striatum and the nucleus accumbens were comprehensively examined for the pattern of modulation of haloperidol-induced c-fos expression by adenosine A(2), histamine H(3) and muscarinic receptor antagonists. Blockade of muscarinic and H(3) receptors resulted in a profound suppression of haloperidol-induced c-fos expression in the dorsolateral part of the striatum. In addition, the H(3) receptor antagonist suppressed the effects of haloperidol in the ventrolateral aspect of the striatum and the rostral parts of the medial striatum. Muscarinic receptor antagonists suppressed haloperidol-induced c-fos expression throughout the shell and in the mid-level of the core of the nucleus accumbens while A(2) and H(3) receptor antagonists did not.We found that the muscarinic and H(3) receptor antagonists suppress the induction of c-fos by haloperidol in the dorsolateral aspect of the striatum, an area implicated in the development of extrapyramidal motor symptoms following chronic haloperidol treatment. By contrast, haloperidol-induced c-fos expression in the nucleus accumbens, an area implicated in the therapeutic effects of haloperidol, was suppressed by the muscarinic receptor antagonist, but not by the H(3) receptor antagonist. Therefore we conclude that H(3) receptor modulation may provide a useful therapeutic target in future efforts to minimize neuroleptic-induced motor side effects.

Animals↗
PubMed2002

Lowering anti-dsDNA antibodies--what's new?

Antibodies to dsDNA are specific to SLE and are pathogenic, both due to their ability to deposit in tissues through a variety of mechanisms, and to their ability, when present in immune complexes, to activate inflammatory cells. The relationship of serum anti-dsDNA antibody levels to disease activity is a complex one and the factors that determine whether or not such antibodies will be pathogenic in an individual SLE patient are incompletely understood. Although anti-dsDNA antibodies can be made by naïve B cells and B cells belonging to the B1 and marginal zone subsets, pathogenic anti-dsDNA antibodies have the hallmarks of germinal center development and exposure to T cell help, including accumulation of somatic mutations and class switching to the IgG isotype. Epitope spreading may result in aquisition of cross-reactivities with multiple target organ antigens and aquisition of a memory phenotype will allow these B cells to acquire antigen presentation functions that amplify the autoreactive response. In the early stages of disease, or after remission induction protocols, autoreactive B cells may be susceptible to treatments that target T cell costimulation or that deplete or tolerize naïve and mature B cells. Therapeutic approaches targeting innate immune responses or regulatory T cells are starting to be tested in pre-clinical models. In later disease stages, memory and plasma cell accumulation may render patients more resistant to this type of therapeutic approach. Deposition of anti-dsDNA antibodies in target tissues can stimulate an inflammatory cascade that leads to tissue damage. A number of murine models have now been developed that show that interruption of this cascade can prevent or reverse such damage. This type of approach may be beneficial for individuals with established disease. As we learn more about the specific defects that cause SLE, it may become possible to individualize therapy based on patient specific biologic markers.

Animals↗
PubMed2001

Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas.

The translocation of particulate matter across the gastrointestinal tract is now a well documented phenomenon offering new potential for the delivery of drugs with poor dissolution profiles and labile chemistries via encapsulation in biodegradable nanoparticles. The last few years have seen an acceleration in the number of publications describing the varying facets of this approach and the multidisciplinary nature of this field. This review delineates data from this rather fragmented area and from cognate fields to provide a physicochemical viewpoint of the importance of surface chemistries of oral drug delivery vehicles and their interactions in and with gut contents prior to uptake. The role of lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is discussed. The exciting potential of molecular encapsulation of drugs via dendrimers and star branched molecules is discussed in the context of nanotechnological applications for the oral route. Evolving vistas include a better understanding of the plasticity of the intestinal epithelium and M-cell induction as well as the influence of disease states on particulate uptake. In this review we address a number of issues deemed vital to an understanding of the subject including (i) some background knowledge on particulate uptake (the subject of several reviews), (ii) factors affecting uptake such as diameter and surface charge and character, (iii) the dynamic nature of particle interactions in the gut, (iv) the dynamic nature of the processes of capture, adhesion, uptake, transcytosis and translocation, and (v) the influence of surface ligands.

Administration, Oral↗
PubMed2001

Fluorometric method for the simultaneous quantitation of differently-sized nanoparticles in rodent tissue.

The oral absorption and systemic translocation of particulate matter via the gastrointestinal tract has been shown by a number of laboratories using a wide variety of particles in different animal species. While there is debate on the magnitude of particle intestinal translocation, which is encumbered by the differing experimental protocols, particularly the method of quantitation of absorbed material, few have sought to examine the pharmacokinetic aspects of particle absorption. We describe in this communication the development of a simple and a rapid fluorometric assay of quantifying tissue-laden fluorescent nanoparticles that is able to isolate, detect and quantify the presence of two or more particle populations differing both in their size and fluorescent label. Six types of polystyrene nanoparticles incorporating different fluorescent markers were spiked in whole livers. The fluorophores were extracted using our previously developed method of freeze-drying the tissue and using chloroform as the extractive solvent. Only two types of particle populations, orange-labelled 40 nm and Fluoroscein-emitting 500 nm nanoparticles, were sufficiently recoverable and provided a high signal-to-noise ratio for further work. The amount of tissue and type of biological tissue type also impacted on the nanoparticle recovery and detection, reflecting, perhaps, the quenching effects of interacting tissue-derived molecules. In addition, the results also indicate that the use of nanoparticles incorporating fluorescent dyes that have emission over 500 nm overcome the tissue interfering autofluorescence for low doses of nanoparticles. The use of this fluorometric method has several advantages compared with other modes of quantitation in that it is rapid, non-radioactive and the marker is non-leaching. More importantly, it allows the simultaneous detection of multiple fluorophores such that two or more different fluorescent particle populations can be detected in the same sample. This may enable the uncharted area of pharmacokinetic parameters, such as the impedance, augmentation or site of gut uptake of differently sized particles to be studied.

Animals↗
PubMed2001

Intraspinal neurenteric cysts--report of three paediatric cases.

BACKGROUND: Neurenteric cysts are rare congenital lesions of the spine and are lined with entodermal epithelium. They result from anomalous endodermal-neuroectodermal adhesion in the 3rd week of embryonic life with persistence of canal of Kovalevsky. The nature of the eventual abnormality depends on the extent to which this adhesion subsequently disappears. Persistence of the entire tract results in the extreme form of combined anterior and posterior spina bifida with dorsal enteric fistula and persistence of only a part of the tract producing the isolated intraspinal cyst. The most common location is the cervico-dorsal region, and usually it lies ventral to the spinal cord. The lumbosacral location is uncommon. Associated vertebral anomalies, gut cysts, bowel duplication, the presence of keratin markers and mucin-secreting cuboidal or columnar intestinal epithelium in their walls confirm their entodermal origin. PATIENTS: We describe here three unusual cases of neurenteric cysts in patients aged 5-18 years who had already had symptoms for some time. One of these had a cyst sited predominantly in the sacral canal, another presented with a lumbar neurenteric cyst, and the third patient had an intradural extramedullary thoracic lesion. Two of these children had associated anomalies, the one with lumbar cyst also having a lipomeningomyelocele and spina bifida while the other also had deformed vertebrae. All three patients underwent laminectomy and gross excision of the cysts through a posterior approach. RESULTS AND CONCLUSION: The diagnosis of neurenteric cysts was confirmed by demonstrating mucin-producing cuboidal or columnar epithelium lining the cystic cavity.

Adolescent↗
PubMed2001

Glutamatergic regulation of haloperidol-induced c-fos expression in the rat striatum and nucleus accumbens.

Acute administration of haloperidol induces the expression of the immediate-early gene c-fos in the striatum and nucleus accumbens via dopamine D(2) receptor antagonism. Dopaminergic transmission in the striatum and nucleus accumbens is modulated by glutamate via N-methyl-D-aspartate (NMDA) receptors. Indeed, haloperidol-induced c-fos expression is dependent on NMDA receptor activation in the dorsolateral part of the striatum. However, the role that NMDA receptors play in haloperidol-induced c-fos expression in other functionally distinct areas of the striatum and nucleus accumbens has not yet been established. Therefore, in the present study the entire rostrocaudal extent of the rat striatum and nucleus accumbens was examined to determine the role that NMDA receptors play in haloperidol-induced c-fos expression. Pretreatment with MK-801, a non-competitive antagonist of NMDA receptors, significantly reduced the number of neurons showing c-fos immunoreactivity in the rostral aspect of the dorsolateral striatum and the entire rostrocaudal extent of the ventrolateral striatum following an acute injection of haloperidol. However, the same treatment did not modify the pattern of haloperidol-mediated c-fos expression in the medial or central parts of the striatum. Similarly, MK-801 pretreatment significantly suppressed the number of neurons expressing c-fos immunoreactivity following haloperidol injection in the entire rostrocaudal extent of the shell region of nucleus accumbens, but not in the core region. The results indicate that haloperidol-induced c-fos expression is dependent on NMDA receptors only in the rostral aspect of the dorsolateral striatum and the rostrocaudal extent of the ventrolateral striatum, the areas involved in motor function. The differential role that NMDA receptors play in modulating haloperidol-mediated dopamine D(2) receptor antagonism between motor and associative areas of the striatum may contribute to the development of extrapyramidal symptoms following chronic haloperidol treatment. Furthermore, the attenuation of the haloperidol-induced c-fos expression by MK-801 was restricted to the nucleus accumbens shell, an area often implicated in the therapeutic effect of haloperidol. Therefore, the NMDA-dopamine D(2) receptor interaction may also play a role in mediating the therapeutic effects of haloperidol.

Animals↗
PubMed2001

Role of Bi-pap in acute respiratory failure due to acute exacerbation of COPD.

OBJECTIVE: To assess the efficacy of Bi-level Positive Airway Pressure (Bi-pap), administered by nasal mask in patients with acute respiratory failure due to acute exacerbation of COPD. DESIGN: Prospective non-randomized study in a hospital setting. METHODS: Eighteen patients were recruited from those admitted in the Chest Unit of Jinnah Postgraduate Medical Centre, Karachi with acute exacerbation of COPD. Along with conventional treatment, Bi-pap was administered by a nasal mask. Arterial blood gas analysis, respiratory and heart rate and subjective sensation of dyspnoea, before and during Bi-pap application were monitored. RESULTS: The respiratory rate decreased from 33.2 +/- 5.3/min to 22.0 +/- 3.5 (P < 0.001), heart rate also decreased from 113.2 +/- 7.6/min to 90.2 +/- 11.9 (P < 0.001). A rise in pH was observed from 7.2 +/- 0.09 to 7.4 +/- 0.06 (P > 0.41 n.s.), PaCO2 decreased from 76.5 +/- 15.5 to 51.3 +/- 10.5 (P < 0.001). PaO2 also increased from 52.1 +/- 14.3 to 62.9 +/- 11.5 (P < 0.01). The mean hospital stay was shorter i.e., 10.6 +/- 5.6 days and the hospital mortality rate 11.1%. Bi-pap administered by nasal mask was generally well tolerated with few minor complications. CONCLUSION: Bi-pap is particularly useful in patients presenting with acute respiratory failure due to acute exacerbation of COPD particularly in our setting where invasive ventilation is not easily available.

Aged↗
PubMed2000

Cationic lipid-based delivery system for systemic cancer gene therapy.

A cationic lipid-based gene delivery system composed of N-[(1-(2,3-dioleyloxy)propyl)]-N-N-N-trimethylammonium chloride and cholesterol, at a 4:1 molar ratio, was developed for systemic administration. Plasmid biodistribution and expression were characterized in syngeneic mouse tumor model squamous cell carcinoma VII cells. A reporter gene expression plasmid was used for biodistribution of plasmid and expression. The results showed that lungs and primary tumors were transfected. Fluorescence microscopy showed that fluorescent-labeled transfection complexes were passively targeted to the tumor vasculature and that the endothelial cells internalized the plasmid. Transgene expression was characterized based on duration of expression and dosing schedule. In vivo gene transfer with an interleukin-12 expression plasmid yielded protein levels in blood, lungs, and primary tumor after intravenous administration. Efficacy studies showed that 15 microg of interleukin-12 plasmid was sufficient to produce a gene-specific inhibition of primary tumor growth. These results characterize the vascularity of the tumor model, characterize the in vivo gene transfer properties of the plasmid-based gene delivery system, and show that the transgene expression level was sufficient to elicit a biological response by inhibiting tumor growth.

Animals↗
PubMed2000

Allergic gastroenteropathy in preterm infants.

OBJECTIVES: To determine the clinical presentation, histopathologic features, and outcome of biopsy-proven allergic gastroenteropathy (AGE) in preterm infants. We hypothesized that AGE is a more frequent cause of gastrointestinal disease in this population than previously suspected. STUDY DESIGN: The retrospective portion of the study, from 1992 to 1997, included preterm infants <37 weeks' gestation who underwent biopsy because of suspected AGE. The prospective portion, from January to December 1998, included 20 infants undergoing endoscopy and biopsy because of suspected AGE. RESULTS: Twenty-five infants (12 retrospective/13 prospective) with mean gestational age of 29 weeks at birth and mean postnatal age at diagnosis of 78 days were diagnosed with AGE. Three clinical patterns of presentation were noted: group 1, gastroesophageal reflux disease (n = 5); group 2, non-specific feeding intolerance (n = 8); and group 3, lower gastrointestinal bleeding (n = 12). Ten patients had negative biopsy findings (3 retrospective/7 prospective) and had clinical features indistinguishable from those of groups 1 and 2. Patients in group 3 were most likely to have positive biopsy findings (12 of 12). Fifteen patients responded to a casein hydrolysate formula, and 10 patients required an amino acid-based formula. Patients with AGE who had eosinophilic infiltration and villous atrophy took longer to recover than those with eosinophilic infiltration alone (P <.03). Subsequently, most have tolerated formula challenges and are currently tolerating cow's milk. CONCLUSIONS: AGE may be an under-recognized cause of gastrointestinal symptoms in preterm infants. Confirmation with endoscopy and biopsy can be done safely and provides the basis for appropriate dietary management.

Follow-Up Studies↗
PubMed2000

Floquet exponents of underdamped josephson ladders: A comparison with predictions of the discrete sine-gordon equation

We calculate Floquet exponents for phase-locked solutions in ladder arrays of Josephson junctions in zero external field. We assume a resistively and capacitively shunted junction (RCSJ) model, and we allow for critical current anisotropy between the horizontal and vertical junctions. The ladders range in size from 5 to 30 plaquettes and are biased along the rungs with uniform dc bias currents. The Floquet exponents quantify the stability of the solutions and are calculated numerically for the RCSJ model as a function of junction capacitance (beta(c)) as well as critical current anisotropy (Lambda). We also model the array with the discrete sine-Gordon (DSG) equation, and we are able to calculate the exponents analytically in that case. We find the analytic results from the DSG equation agree quantitatively with the numerical results from the RCSJ model over a wide range of beta(c) and Lambda values and even agree qualitatively for beta(c)-->1 and Lambda-->0. Based on the analytic result we argue that perturbations in the array are damped by the small-angle phase oscillations of the underlying lattice (the "phonons" of the lattice), and like a classical harmonic oscillator with damping, each phonon mode has a crossover (as a function of decreasing beta(c) or Lambda) from underdamped to overdamped dynamics. Such crossover behavior is clearly visible in the results for the Floquet exponents and is manifested as a maximum in the Floquet exponent as a function of the junction capacitance. This intriguing result speaks to the opportunity, in principle, of tuning the capacitance such as to optimize the stability of the phase-locked solutions.

Journal Article↗