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Biomedical subjects

M A Khan

Publications and source records attributed to M A Khan.

At least 19 recordsLinked to original sources

Causes of blindness and visual impairment in Pakistan. The Pakistan national blindness and visual impairment survey.

OBJECTIVE: To determine the causes of blindness and visual impairment in adults (> or =30 years old) in Pakistan, and to explore socio-demographic variations in cause. METHODS: A multi-stage, stratified, cluster random sampling survey was used to select a nationally representative sample of adults. Each subject was interviewed, had their visual acuity measured and underwent autorefraction and fundus/optic disc examination. Those with a visual acuity of <6/12 in either eye underwent a more detailed ophthalmic examination. Causes of visual impairment were classified according to the accepted World Health Organization (WHO) methodology. An exploration of demographic variables was conducted using regression modeling. RESULTS: A sample of 16 507 adults (95.5% of those enumerated) was examined. Cataract was the most common cause of blindness (51.5%; defined as <3/60 in the better eye on presentation) followed by corneal opacity (11.8%), uncorrected aphakia (8.6%) and glaucoma (7.1%). Posterior capsular opacification accounted for 3.6% of blindness. Among the moderately visually impaired (<6/18 to > or =6/60), refractive error was the most common cause (43%), followed by cataract (42%). Refractive error as a cause of severe visual impairment/blindness was significantly higher in rural dwellers than in urban dwellers (odds ratio (OR) 3.5, 95% CI 1.1 to 11.7). Significant provincial differences were also identified. Overall we estimate that 85.5% of causes were avoidable and that 904 000 adults in Pakistan have cataract (<6/60) requiring surgical intervention. CONCLUSIONS: This comprehensive survey provides reliable estimates of the causes of blindness and visual impairment in Pakistan. Despite expanded surgical services, cataract still accounts for over half of the cases of blindness in Pakistan. One in eight blind adults has visual loss from sequelae of cataract surgery. Services for refractive errors need to be further expanded and integrated into eye care services, particularly those serving rural populations.

Adult↗

Thermal destabilization of stem bromelain by trehalose.

Trehalose, a naturally occurring osmolyte, is considered as a universal protein stabilizer. We investigated the effect of the disaccharides, trehalose and sucrose, on the thermal stability and conformation of bromelain. To our surprise, bromelain in the presence of 1 M trehalose/sucrose was destabilized under thermal stress. The average Tm values as determined by UV spectroscopy and CD spectropolarimetry decreased by 5 degrees and 7 degrees C for bromelain in 1 M sucrose or trehalose solutions, respectively. The enzyme was also found to inactivate faster at 60 degrees C in the presence of these osmolytes. The tertiary and secondary structure of bromelain undergoes small changes in the presence of sucrose/trehalose. Studies on the binding of these osmolytes with the native and the heat denatured enzyme revealed that sucrose/trehalose lead to preferential hydration of the denatured bromelain as compared to the native one, hence stabilizing more the denatured conformation. This is perhaps the first report on the destabilization of a protein by trehalose.

Ananas↗

Chemical treatments to reduce antinutritional factors in salseed (Shorea robusta) meal: effect on nutrient digestibility in colostomized hens and intact broilers.

This study investigated the effects of chemical treatments of salseed meal (SSM) on nutrient digestibility and digestive enzymes in colostomized hens and intact broilers. Finely ground SSM was treated (820 mL/ kg of SSM DM) with distilled water (pH 5.3), 0.67 M acetic acid (pH 2.4), or 0.67 M sodium hydrogen carbonate (pH 8.2), and incubated for 12 h at 37 degrees C. Five isonitrogenous and isocaloric diets each for colostomized hens (25.6 g of N/kg of DM and 12.5 MJ/kg of DM) and for broilers (33.6 g of N/kg of DM and 12.3 MJ/kg of DM) were formulated. For each group, 1 of these diets was wheat-based (control) whereas the other 4 were SSM-based diets (untreated SSM or SSM treated with water, acetic acid, and sodium bicarbonate). Inclusion of SSM in diets markedly reduced apparent protein and starch digestibility in hens and broilers. Chemical treatments of SSM improved the protein and starch digestibilities in colostomized hens and broilers. Treatment of SSM with alkali reduced the pancreatic hypertrophy in broilers that was observed when SSM was included in the diet. Inclusion of SSM in broiler diets did not affect pancreatic trypsinogen activity; however, chymotrypsinogen and alpha-amylase activities were depressed with its inclusion. Activities of these enzymes were improved by all chemical treatments of SSM. Dietary inclusion of SSM in broiler diets depressed the activities of trypsin, chymotrypsin, and alpha-amylase in the jejunal digesta. Alkali treatment proved to be the most effective in reducing the adverse effects of SSM upon trypsin and chymotrypsin activities. The hens receiving SSM in their diets produced eggs with discolored yolks (dirty greenish-yellow). In conclusion, nutrient digestibility, and pancreatic and intestinal enzymes were markedly depressed with the inclusion of SSM in the diets of the fowl. Bicarbonate was the most effective treatment to improve nutrient digestibility and mitigate, to some extent, the poor digestion of SSM.

Animal Feed↗

Clinical guidelines to diagnose smear-negative pulmonary tuberculosis in Pakistan, a country with low-HIV prevalence.

OBJECTIVES: To develop and validate clinical guidelines for diagnosis of smear-negative pulmonary tuberculosis (TB) in developing countries with low-HIV prevalence. METHODS: We developed diagnostic guidelines for smear-negative TB. Clinical diagnoses based on these guidelines were compared with sputum culture, chest X-rays and reports of an expert panel. RESULTS: The guidelines achieved a sensitivity of 0.59 [confidence interval (CI) 0.46-0.66] and a specificity of 0.86 (CI 0.84-0.88) in diagnosing smear-negative TB. A total of 6.8% of patients who initially improved after a course of antibiotics were later confirmed to have TB. Clinicians detected an abnormal chest X-ray in 92% (CI 88-96%) and radiological signs of pulmonary TB in 98% (CI 94-100%) of cases. CONCLUSIONS: Our experience highlights a number of dilemmas faced in developing, testing and implementing diagnostic guidelines in poorly resourced conditions. Using radiological criteria for TB and appropriate training can help in improving the diagnostic skills of primary care clinicians working in low-HIV settings with access to X-ray facilities. But a significant number of apparently smear-negative TB cases may in fact be smear positive and TB programmes should focus on improving the quality of direct acid-fast bacilli microscopy. The value of an antibiotic trial is questionable due to the relatively large number of false negatives generated by this approach.

Adolescent↗

Cataract blindness and visual outcome of cataract surgery in a tribal area in Pakistan.

AIM: To estimate the rates of cataract blindness and cataract surgical coverage and to assess the visual outcome of cataract surgery among individuals aged > or =50 years in Orakzai Agency, Pakistan. METHODS: 1600 individuals aged > or =50 years were selected using probability proportional to size sampling. The main outcome measure was bilateral cataract blindness which was defined as visual acuity of <3/60 in the better eye with best available correction and with obvious central lens opacities/absence of red reflex in both eyes. RESULTS: A total of 1549 people were examined; the coverage rate was 96.8%. Of individuals who were examined, 958 (61.8%) were men. The overall prevalence of bilateral cataract blindness was 4.8% (95% CI: 3.8% to 5.9%). Women had a 2.1-fold greater prevalence of bilateral cataract blindness than men (7.1% (5.0% to 9.2%) v 3.4% (2.3% to 4.6%); p = <0.0001). However, cataract surgical coverage rates were lower for women than men. The overall quality of previous cataract surgery was poor: 43.1% eyes with cataract surgery had VA <6/60. 73.3% people with bilateral cataract blindness reported they could not undergo cataract surgery because they were too poor to afford its cost. CONCLUSION: The unacceptably high rates of cataract blindness and poor affordability and visual outcome of cataract surgery calls for the establishment, in the agency, of static cataract surgical services that are high quality, affordable, and gender sensitive.

Age Distribution↗

Tuberculosis patient adherence to direct observation: results of a social study in Pakistan.

A randomized controlled trial was carried out in Pakistan in 1999 to establish the effectiveness of the direct observation component of DOTS programmes. It found no significant differences in cure rates for patients directly observed by health facility workers, community health workers or by family members, as compared with the control group who had self-administered treatment. This paper reports on the social studies which were carried out during and after this trial, to explain these results. They consisted of a survey of all patients (64% response rate); in-depth interviews with a smaller sample of different types of patients; and focus group discussions with patients and providers. One finding was that of the 32 in-depth interview patients, 13 (mainly from the health facility observation group) failed to comply with their allocated DOT approach during the trial, citing the inconvenience of the method of observation. Another finding was that while patients found the overall TB care approach efficient and economical in general, they faced numerous barriers to regular attendance for the direct observation of drug-taking (most especially, time, travel costs, ill health and need to pursue their occupation). This may be one of the reasons why there was no overall benefit from direct observation in the trial. Provider attitudes were also poor: health facility workers expressed cynical and uncaring views; community health workers were more positive, but still arranged direct observation to suit their, rather than patients', schedules. The article concludes that direct observation, if used, should be flexible and convenient, whether at a health facility close to the patient's home or in the community. The emphasis should shift in practice from tablet watching towards treatment support, together with education and other adherence measures.

Data Collection↗

ASAS/EULAR recommendations for the management of ankylosing spondylitis.

OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Anti-Inflammatory Agents, Non-Steroidal↗

Acute sarcoid arthropathy.

A case of middle aged female with acute arthritis, mediastinal lymphadenopathy and diabetes mellitus is described. The patient underwent mediastinal lymph node biopsy and was diagnosed as having acute sarcoidosis (Lofgrens syndrome). She was treated with systemic steroids and responded well.

Acute Disease↗

Pregnancy spacing and maternal morbidity in Matlab, Bangladesh.

OBJECTIVE: The study examines the relationship between pregnancy spacing and seven measures of maternal morbidity in Matlab, Bangladesh. METHOD: The study analyzes maternal morbidity data on 11,122 women who visited a health center during their third trimester of pregnancy between 1996 and 2002. Adjusted odds ratios were obtained through logistic regression analysis to assess the effects of pregnancy intervals of differing lengths while holding constant other influences (six variables) on maternal morbidity. RESULTS: After controlling these variables, pre-eclampsia and high blood pressure are significantly more likely for women with preceding inter-pregnancy intervals of less than 6 months or 75 months or more compared to those with intervals of 27-50 months. Premature rupture of membranes is significantly more likely following inter-pregnancy intervals of 6-14 months, and edema is significantly more likely following inter-pregnancy intervals over 50 months. CONCLUSION: Short and long inter-pregnancy intervals are associated with increased incidence of some maternal morbidities.

Adult↗

Choice and availability of takeaway and restaurant food is not related to the prevalence of adult obesity in rural communities in Australia.

OBJECTIVES: To establish whether choice and availability of takeaway and restaurant food consumption are associated with increased obesity. DESIGN: Crossroads Undiagnosed Disease Study: a cross-sectional study undertaken between June 2001 and March 2003. SETTING: A regional centre and six shire capitals of variables size in rural Victoria, Australia. PARTICIPANTS: In total, 1454 residents of randomly selected households. MEASUREMENTS: Obesity (by body mass index (BMI) or waist circumference), weekly recreational activity, self-reported frequency of takeaway consumption, number of local takeaway and restaurant food outlets in the area. RESULTS: The prevalence of obesity ranged from 25.5-30.8% and was higher than the general Australian population among both men and women. Those in the regional centre were less likely than those in large and small shire capitals to participate in recreational activity of 150 min or more (39.7 vs 48.4%, 46.0% respectively, P=0.023) and yet reported better access to facilities and amenities for physical activity. Recreational activity of > or =150 min/week was associated with 0.75 (0.58-0.97) fold less risk of obesity. BMI was unrelated to takeaway consumption. Waist circumference was significantly lower among those eating no takeaways, but similar whether takeaways were consumed <1/month or > or =1/week. Increased takeaway consumption was associated with increased consumption of higher fat preparations of dairy and meat products. Availability of takeaway outlets and restaurants was unrelated to obesity. CONCLUSION: The obesity epidemic exists among those without significant consumption of or availability to takeaway foods. In a setting of easy availability of food, the obesity epidemic relates strongly to reduced physical activity, but not to consumption of takeaway food.

Age Factors↗

Expectant management: an option for localized prostate cancer.

Localized prostate cancer demonstrates tremendous heterogeneity in the natural history of the disease. To this end, although prostate cancer may be present histologically in nearly 30% of all men above the age of 50 y, the lifetime risk of developing clinically significant disease is 18% (one in six). Furthermore, the lifetime risk of dying from prostate cancer is less than 4%. Therefore, in order to avoid unnecessarily treating potentially insignificant prostate cancer, the concept of expectant management has been considered for this disease. In this brief review, we discuss the evolution of expectant management for men with localized prostate cancer.

Humans↗

Camptomelic dysplasia with sex reversal.

Camptomelic dysplasia is a disorder of the newborn characterized by congenital bowing and angulation of long bones together with other skeletal and extraskeletal defects. The affected newborn had dysmorphic features with bowing of the legs and bilateral talipes equinovarus. Radiology showed marked anterior bowing of both tibia with disproportionately short fibula, anterolateral bowing of the femurs and wide pelvic outlet with small iliac wings. She had sex reversal with normal female genitalia and 46, XY karyotype. Camptomelic dysplasia is generally considered to be a lethal skeletal dysplasia and most patients die in the neonatal period due to severe respiratory distress. Survivors may have learning difficulties, developmental delay, conductive hearing loss, myopia and recurrent chest infections. Because of its high associated mortality, prenatal diagnosis of camptomelic dysplasia is mandatory. The birth of a child with skeletal dysplasia is an emotionally difficult experience for parents.

Abnormalities, Multiple↗

Preparation and in vitro characterization of a semi-solid dispersion of flurbiprofen with Gelucire 44/14 and Labrasol.

Flurbiprofen is characterized by low solubility in water and has been implicated in causing gastro intestinal ulceration. The purpose of this study was to increase the dissolution characteristics of flurbiprofen by preparing a semi-solid dispersion with Gelucire 44/14 and Labrasol (F1) in hard gelatin capsules. The results were evaluated by comparing several in vitro parameters with powdered drug filled into hard gelatin capsules. The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; citrate buffer pH 4.5; phosphate buffers pH 6.8 and 7.2, and water). Characterization of semi-solid dispersions and physical mixtures was performed using Fourier transform-infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), particle size analysis and turbidity measurement. The results suggest that all semi-solid dispersions of flurbiprofen showed a remarkable improvement in the rate and extent of drug dissolution. The dissolution of F1 exhibited significant improvement in all dissolution media at different pH. The dissolution of flurbiprofen within 30 min in pH 1.2 was (55%), in pH 4.5 67%, pH 6.8 96%, pH 7.2 98% and in water 88%. FT-IR indicated no strong drug: excipient interactions, and DSC studies indicated a loss of crystalline nature of the drug. The particle size analysis revealed an average size diameter from 194 to 278 nm. Therefore, a semi-solid dispersion of flurbiprofen with Gelucire and Labrasol may have the potential of improved bioavailability because of the enhanced in vitro properties.

Anti-Inflammatory Agents, Non-Steroidal↗

Rapid immunochromatography-based detection of mixed-species malaria infection in Pakistan.

We report the identification of mixed Plasmodium infections in four recent patients with malaria clinically refractory to empiric chloroquine therapy using the rapid antigen detection kit, NOW ICT Malaria Pf/Pv. A rapid in vitro immunodiagnostic test, the NOW ICT Malaria Pf/Pv test kit was used for the detection of circulating Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) antigens in whole blood. Peripheral blood microscopy confirmed mixed-species infection in all the cases. Thick and thin peripheral blood films were made and stained with Giemsa stain and examined by both hospital laboratory staff and an experienced parasitologist who was blinded to the results of the rapid malarial antigen tests. Four recent patients (all male; mean age, 24 years) with mixed malarial infection were identified. All the subjects were males working for an oil company in a coastal area of Pakistan, and all had been diagnosed presumptively with malaria based on clinical grounds (without microbiologic confirmation), and were treated empirically with chloroquine without clinical response. Semiquantitative malaria counts via microscopy were as follows: P. vivax, scanty (2 patients) and moderate (2 patients); for P. falciparum--scanty (1 patient), moderate (2 patients), and heavy (1 patient). The present case series, although limited by the small number of patients with proven mixed P. falciparum-P. vivax infection, highlights the usefulness of the rapid antigen test in a highly malarious region of Pakistan where chloroquine resistance is prevalent. Although there was full concordance between the results of blood smear microscopy and rapid antigen testing, these techniques are potentially most useful when there is a discrepancy with microscopy findings. Accurate and rapid diagnosis of parasites, particularly in cases of mixed P. falciparum and P. vivax infection, is of immense importance for individual patient management and in reducing the burden of disease, especially in regions of chloroquine resistance.

Adult↗

Concurrent malaria and enteric fever in Pakistan.

INTRODUCTION: The precise incidence of concurrent malaria and enteric fever in most geographical areas is largely unknown, and no data on such an association exists in Asia. Because both malaria and enteric fever are hyperendemic in Pakistan, we sought to determine the frequency, epidemiology, and clinical and laboratory features of dual malaria and enteric fever in a tertiary care setting. METHODS: We conducted a retrospective case-control study of 1,891 patients hospitalised with malaria over a ten-year period and identified 21 patients with concurrent culture-proven enteric fever. RESULTS: Cases with dual infection had significantly more gastrointestinal symptoms at the time of admission, including nausea, vomiting, abdominal pain, and/or diarrhoea compared to matched control subjects with uncomplicated malaria (p-value is less than 0.006). Cases were more likely to have a continuous rather than intermittent fever (p-value is less than 0.0001), delayed defervescence in response to antimalarial treatment (p-value is less than 0.006), normal or low white blood cell counts (p-value is less than 0.04), relatively higher platelet counts among cases versus control (p-value is less than 0.05) and serum haemoglobin (p-value is less than 0.06), elevated alanine aminotransferase levels (p-value is less than 0.02), and a prolonged hospital stay (p-value is less than 0.03). The negative predictive values for gastrointestinal symptoms, continuous fever pattern and delayed defervescence were 80 percent, 72 percent and 74 percent, respectively. CONCLUSION: Patients with malaria who have marked gastrointestinal symptoms, continuous pattern of fever and persistence of fever for more than 24 hours after appropriate antimalarial therapy, should be investigated or empirically treated for concurrent enteric fever. The absence of the above clinical features in patients with uncomplicated malaria should reassure physicians that there is no concurrent typhoid fever.

Adolescent↗

Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity.

OBJECTIVE: To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. METHODS: MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. RESULTS: None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. CONCLUSION: These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.

Adult↗

Bioavailability assessment of salbutamol sulfate suppositories in human volunteers.

The purpose of this investigation was to evaluate the bioavailability of three salbutamol sulfate suppository formulations. The formulations were; 2 mg salbutamol sulfate in Suppocire NA base containing 6% Eudispert gel (F1), 2mg salbutamol sulfate in Witepsol H15 base containing 3% methyl cellulose gel (F2), and 2 mg salbutamol sulfate in Witepsol W25 base containing 3% methyl cellulose gel (F3). The formulations were administered via rectal route in six healthy male adult volunteers. The bioavailability of the three suppository formulations was compared with the oral bioavailability of salbutamol sulfate 2mg tablets (F4). Six volunteers participated in a four-way crossover study, where each study was separated from the other by an interval of 1 weak. Venous blood samples of 5 ml were taken immediately before dosing and after predetermined time intervals of 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 and 8 h. The result showed that Cmax +/- S.D. observed were 12.96 +/- 2.11, 14.78 +/- 2.33, 10.02 +/- 1.42 and 11.51 +/- 1.22 ng ml(-1) for F1, F2, F3 and F4, respectively. The Tmax +/- S.D. were found to be 1.91 +/- 0.20, 1.83 +/- 0.26, 2.50 +/- 0.00 and 2.67 +/- 0.24 h for F1, F2, F3 and F4, respectively. AUC +/- S.D. values were 40.25 +/- 1.88, 42.16 +/- 1.55, 28.62 +/- 1.98 and 37.63 +/- 1.44 ng h per ml for F1, F2, F3 and F4, respectively. The relative bioavailabilities of the investigated formulations were 112.04, 106.96 and 76.06 for formula F2, F1 and F3, respectively, when compared with the oral preparation (F4). The finding indicates that the bioavailability of salbutamol sulfate can be enhanced by delivering it rectally with Suppocire NA base containing 6% Eudispert gel or with Witepsol W25 base containing 3% methyl cellulose to match that of oral tablets. Salbutamol sulfate can be rectally administered in patients who are less compliant with the oral administration.

Adult↗