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Biomedical subjects

N Safdar

Publications and source records attributed to N Safdar.

14 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Pharmacokinetic-pharmacodynamic comparison of amphotericin B (AMB) and two lipid-associated AMB preparations, liposomal AMB and AMB lipid complex, in murine candidiasis models.

It is generally accepted that the lipid formulations of amphotericin B (AMB) are not as potent as conventional AMB on a milligram-per-kilogram basis. We used a neutropenic murine disseminated candidiasis model to compare the in vivo potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC) pharmacodynamically. The pharmacokinetics of the antifungals were examined in serum and in three organs commonly seeded in disseminated candidiasis (kidneys, liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen studies were used with each of the compounds. Determinations of the numbers of CFU in the kidneys were performed following the administration of three escalating single doses of the polyenes at various times over 48 h. The areas under the time-kill curves (AUTKs) for each dose level of the drugs were compared by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five Candida isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The organism burdens in the mouse kidneys were similarly used as the treatment end point. Additional multiple regimen-dosing-studies were performed with a single Candida albicans isolate, and the microbiologic outcomes in four internal organs (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h). The relationship between the dose and the drug exposure expressed by the pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed by using a maximum-effect model. ANOVA was used to compare the drug exposures necessary to achieve the 25% effective dose (ED25), ED50, ED75, and 1 log10 killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent than either ABLC or L-AMB. The time-kill curves for both lipid formulations were very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold more potent than each of the lipid formulations against five Candida isolates in the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in the other end organs. The difference in pharmacokinetics in serum accounted for much of the difference in potency between AMB and ABLC (ratio of serum ABLC area under the curve of effective doses to serum AMB area under the curve of effective doses, 1.2). The differences in the kinetics in the various end organs between AMB and L-AMB were better at explaining the disparate potencies at these infection sites (ratio of organ L-AMB area under the curve of effective doses to organ AMB area under the curve of effective doses, 1.1).

Amphotericin B↗
PubMed2006

Voriconazole therapeutic drug monitoring.

We report on 28 patients who underwent voriconazole monitoring because of disease progression or toxicity. A relationship (P<0.025) between disease progression and drug concentration was detected. Favorable responses were observed in 10/10 patients with concentrations above 2.05 microg/ml, while disease progressed in 44% (n=18) of patients with concentrations below 2.05 microg/ml.

Adult↗
PubMed2005

Predictors and outcomes of candiduria in renal transplant recipients.

BACKGROUND: The epidemiology of candiduria in renal transplantation is unknown. METHODS: We performed a nested case-control study to evaluate the epidemiology of candiduria in renal transplant recipients at the University of Wisconsin (Madison) over an 8-year period. RESULTS: Renal transplantations were performed on 1738 patients during this period, 192 of whom had 276 episodes of candiduria. Candida glabrata, which was recovered from 98 (51%) of 192 case patients, was the most common pathogen identified. Most case patients were asymptomatic. Independent predictors of candiduria were female sex (odds ratio [OR], 12.5; 95% confidence interval [CI], 6.7-23.0), intensive care unit admission (OR, 8.8; 95% CI, 2.3-35.0), antibiotic use during the month before candiduria (OR, 3.8; 95% CI, 1.7-8.3), presence of an indwelling bladder catheter (OR, 4.4; 95% CI, 2.1-9.4), diabetes (OR, 2.2; 95% CI, 1.3-3.9), neurogenic bladder (OR, 7.6; 95% CI, 2.1-27), and malnutrition (OR, 2.4; 95% CI, 1.3-4.4). Log-rank testing of Kaplan-Meier curves revealed that 60-day, 90-day, and cumulative survival rates were significantly different between case and control patients; there was no difference in the survival rate during the first 30 days after transplantation. A variety of regimens were used for treatment; 119 case patients (62%) underwent removal of the indwelling bladder catheter within 1 week after diagnosis of candiduria. Candiduria cleared in 148 case patients (77%). Treatment of candiduria was not associated with an improved survival rate. CONCLUSIONS: Candiduria occurs commonly in renal transplant recipients. Risk factors for candiduria in such persons are similar to those in hospitalized patients who have not received a transplant. Candiduria is associated with reduced survival rates among persons who have undergone renal transplantation; this is likely a marker for severity of illness. Treatment of asymptomatic candiduria in renal transplant recipients does not appear to result in improved outcome.

Adolescent↗
PubMed2002

Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment.

An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the highest cure rates (67%), with a cost per case only slightly higher than the self-administered group (172 dollars per case cured). This approach should be investigated further, along with other approaches to improving patient compliance.

Adult↗
PubMed1996

Tight-binding inhibitory sequences against pp60(c-src) identified using a random 15-amino-acid peptide library.

A bacteriophage peptide library containing a random 15-amino-acid insert was screened for identification of peptide sequence(s) that bind pp60(c-src). Sequencing the random insert from more than 100 virions indicated that more than 60% of the phage virions that bound to this enzyme contained a GXXG sequence motif in which X was frequently a hydrophobic residue. The GXXG sequence was often repeated as GXXGXXG. Two nonameric peptides were synthesized to determine whether or not the peptide inhibits pp60(c-src) tyrosine kinase activity and the importance of the glycine residues within this sequence. The peptide containing glycine had a Ki of 24 microM, whereas replacing the glycines with proline increased the Ki value to 3.1 mM.

Amino Acid Sequence↗
PubMed1995

Relationship between fractures of the mandibular angle and the presence and state of eruption of the lower third molar.

OBJECTIVES: This study attempted to relate the incidence of fractures at the mandibular angle with the presence and state of eruption of lower third molars. STUDY DESIGN: The records and radiographs of 200 patients with mandibular fractures were examined. The presence and degree of impaction of lower third molars were assessed for each patient and related to the occurrence of fractures of the mandibular angle. Data were analyzed by chi-square statistic and the Student's t test. RESULTS: The incidence of angle fractures was found to be significantly greater when unerupted lower third molars were present (p < 0.001). Bilateral unerupted third molar teeth predisposed to a fracture at the angle significantly more than unilateral unerupted third molars (p < 0.01). Furthermore, the amount of bony space occupied by an unerupted third molar tooth directly related to the weakness of that area of bone (p < 0.001). CONCLUSIONS: This study provides clinical evidence to suggest that unerupted third molar teeth weaken the mandibular angle both quantitatively and qualitatively.

Adolescent↗
PubMed1995

Non-compliance to diet and fluid restrictions in haemodialysis patients.

Compliance with fluid and dietary instructions is a critically significant factor in the health and well-being of haemodialysis patients. Serial measurement of serum potassium (K) and interdialytic weight gain (IWG) were carried out in 50 haemodialysis patients at the Kidney Centre over a period of one month. Sixty-two percent were males. Ages ranged from 19-69 years (mean 49 years). Duration on dialysis varied from 6 months to 9 years. Patients with an IWG > 1.5 Kg and/or serum K+ > 5.5 m Eq/L were defined as non-compliant. Thirty-two patients (64%) were non-compliant in either diet or fluid. In 13 of these cases, both serum K and IWG were elevated. In the remaining 19, only one value was high. Predictors of non-compliance to diet and fluid regimens were older age (81%), males (68%), less education (75%), single (90%) depression (59%) and not feeling responsible for one's own well-being (85%). Attempts to improve compliance should be aimed by exposing the non-compliant group to nutritional and psychosocial therapy.

Adult↗
PubMed1994

Nutritional assessment of patients on maintenance haemodialysis.

Nutritional assessment was carried out on fifty haemodialyzed patients by demographic, anthropometric, biochemical and dietary indices. The mean age of the patients was 49 years with a male to female ratio of 2.3:1. The duration of dialysis ranged from 6 to 40 months with a mean of 25 months. Fifty percent of the patients were moderately nourished based on their body weight 44%, body mass index 40% and mid-arm circumference 66%. Seventy percent patients had albumin and total proteins within the normal range. Blood urea nitrogen, creatinine, cholesterol, potassium and phosphorus did not significantly change from the previous reports. The calorie and protein intake in 60-70% cases was less than recommended. Overall there was a tendency to calorie and to a lesser degree protein malnutrition in our patients. It is suggested that preventing malnutrition by economical, aggressive and ongoing dietary intervention may minimize malnutrition in haemodialyzed patients.

Adult↗
PubMed1994

Detection of cellular proteins that interact with the NF2 tumor suppressor gene product.

The neurofibromatosis type 2 (NF2) gene was recently cloned, and the protein it encodes (merlin) was revealed to belong to a family of proteins that link cytoskeletal components with proteins in the cell membrane. To elucidate the biological function of merlin, we produced a bacterial fusion protein consisting of glutathione S-transferase and merlin and used it to detect five merlin-binding cellular proteins, designated p165, p145, p125, p85 and p70, by a protein-binding assay. p165 and merlin were phosphorylated on serine/threonine residues, and immunoprecipitation showed that p85 bound the native form of merlin. Although the entire merlin-ezrin-radixin-moesin (MERM) homology domain of merlin was found to be essential for binding to all five proteins, the MERM homology domains of ezrin and moesin did not bind to any of the five proteins. Since most reported NF2 mutations are in the region we determined was necessary for binding, the mutations probably impair binding. Therefore, the formation of the protein complex is probably crucial for tumor suppression.

Base Sequence↗