Biomedical subjects
Publications and source records attributed to S N Khan.
Although a cure for spinal cord injuries does not currently exist, advances have been made in the field of spinal cord regeneration. This article discusses the pathophysiology of spinal cord injury, animal models, and strategies for restoration and regeneration of the spinal cord.
Gene therapy is a novel therapeutic modality for repair and regeneration of musculoskeletal tissues, including the spine. Various methods for therapeutic gene transfer are presented in this article. Several studies in which gene transfer has been used specifically to enhance spine fusion in animal models are reviewed.
BACKGROUND: In 1971 we published a survey of pediatricians' knowledge, attitudes, and practices relative to the field of allergy. This current survey was conducted to determine how these attitudes and practices have changed over the past 27 years. METHODS: Our survey, consisting of 17 questions, was sent to 250 board certified pediatricians in the St. Louis area. Seven of the questions were similar to those in the 1971 survey, while the other ten were new questions which we thought were pertinent to the field of allergy currently. RESULTS: In 1971, 75% of the pediatricians felt the specialty of allergy had great or moderate importance for the practice of pediatrics compared with 99% in 1998. In 1998, the number of physicians who felt that there was at least some value to skin testing had increased from 1971, although, only 36% felt it had great value. In 1971, 23% of pediatricians performed their own skin tests compared with 3% in 1998. Nine percent indicated that they had never referred a patient to an allergist in 1971, compared with 2% in 1998. Our new questions looked at to whom respondents were more likely to refer patients with: (1) asthma (68% allergy, 27% pulmonary, 4% both), (2) urticaria (53% allergy, 41% dermatology, 2% both), (3) chronic eczema (45% allergy, 50% dermatology, 2% both), and (4) chronic sinusitis (24% allergy, 74% otolaryngology, 2% both). Older physicians placed greater importance on the field of allergy and skin testing and were more likely to refer to an allergist than physicians under the age of 40 years. CONCLUSION: Our results indicate that although there has been significant change in 27 years, allergists must be more aggressive in developing the knowledge, attitudes, and practices of physicians relative to the field of allergy.
Osteoporosis is a disorder of decreased bone mass, microarchitectural deterioration, and fragility fractures. Osteoporosis is widespread and can affect people of all ethnic backgrounds and many older women and men. An essential element in preventing osteoporosis is the achievement of normal peak bone mass. Adequate nutrition, appropriate calcium and vitamin D intake, regular menstrual cycles and a well balanced exercise program of exercise are essential elements in achieving peak bone mass. At menopause women undergo accelerated bone loss. Thereafter, women and men gradually lose bone mass. A loss of one standard deviation give rise to an enhanced twofold risk of spine fractures or a 2.5 risk of hip fracture. Bone mass is determined by dual energy x-ray absorptiometry, quantitative computed tomography scan, and a peripheral ultrasound. Dual energy x-ray absorptiometry has outstanding precision (within 1% to 2%), and has the ability to show the efficacy of drug intervention. Peripheral measurements may identify osteoporosis but only have a 70% correlation with hip and spine bone mass. Dual energy x-ray absorptiometry determines bone mass in a patient but the bone collagen breakdown products (N-telopeptide crosslinks) establish the current rate of bone loss. Major risk factors leading to fragility fracture include low body weight, history of fracture, family history of osteoporosis, and smoking. All individuals should ingest adequate calcium and vitamin D, exercise, and prevent falls. Women with low bone mass, high urinary bone collagen breakdown products, and/or major risk factors should consider hormone replacement therapy or a selective estrogen receptor modulator (Evista), calcitonin and bisphosphonates (alendronate). These agents successfully increase bone mass and limit fracture risk. Men at risk for fragility fractures respond similarly as women to alendronate and calcitonin. Although vertebral compression fractures can occur spontaneously, hip fractures are attributable to low bone mass coupled with a fall. Hence, fall prevention programs in addition to medical treatment are critical in the prevention of fragility fractures.
Three rare beta-thalassemia mutations, not reported previously in Asian Indians or the Pakistani population, were identified by single strand conformation polymorphism analysis followed by direct sequencing. Two mutations, IVS-II-848 (C-->A) and initiation codon (ATG-->ACG), were found in the homozygous condition in patients belonging to Balochi and Sindhi ethnic groups of Pakistan, together with heterozygous and homozygous alpha(-3.7) deletions, respectively. A frameshift mutation at codon 44 (-C) was identified in a patient belonging to the Gujrati ethnic group together with IVS-I-1 (G-->T) and a normal complement of four a-globin genes. Haplotype analysis was performed to identify the chromosomal background associated with these mutations, and for tracing the origin and spread of these mutations.
We have identified a rare alpha2-globin chain variant, Hb Sallanches [alpha104(G11) Cys-->Tyr], in a Pakistani family having three homozygous patients with transfusion-dependent Hb H disease. This variant, previously reported in a French patient and a West Indian homozygous patient with Hb H disease, is due to a mutation at codon 104 (TGC-->TAC). This is the third case of Hb Sallanches and the first case with three homozygous patients reported in Pakistan. Due to the different ethnic origins of the patients, it is very likely an independent mutation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Beta-thalassemia is one of the most common inherited hemoglobin disorders in Pakistan. The carrier frequency is estimated to be 5.4%. To determine the spectrum of beta-globin gene defects causing beta-thalassemia, we have analyzed a representative sample of 602 alleles from six ethnic groups in Pakistan; 99.2% alleles were characterized, while 0.8% remained unidentified. The spectrum of mutations is heterogeneous and we have found 19 different mutations in all ethnic groups. The four most common mutations, IVS-I-5 (G-->C) (37.7%), codons 8/9 (+G) (21.1%), the 619 bp deletion (12.4%), and IVS-I-1 (G-->T) (9.5%), account for 80.7% of the alleles. There are differences between the ethnic groups and also between provinces. In the four provinces of Pakistan, the IVS-I-5 (G-->C) mutation is more prevalent in Sindh and Balochistan, bordering India in the south and Iran in the southwest, while the codons 8/9 (+G) mutation is more common in the Punjab and the North West Frontier Province, bordering India in the northeast and Afghanistan, respectively. The 619 bp deletion is high (46%) in Gujratis and Memons residing in the Province of Sindh, neighboring the Indian Gujrat.
Explore the source record for details and available documents.
A set of procedures, based on DNA analysis, has been developed to detect deletions and point mutations causing Beta thalassemia in the Pakistani population. These procedures can be used to analyze the presence of relevant changes in DNA, thus providing a reliable means for screening the high risk families, to provide them genetic counselling and prenatal diagnosis during early pregnancy. We have identified two mutations IVS-1 nt.5 (G--C) and codon 8-9 (+G) in 4 of the 6 families analyzed for these mutations.
In this study 234 children with shigellosis were evaluated during a 6-year period. The ages ranged from 2 days to 13 years (mean, 3.4 years). Sixty percent of the children were in the 1- to 4-year age group. One hundred four children were hospitalized and 130 were outpatients. Most cases of shigellosis presented during the months of April-May and September-November. Shigella flexneri accounted for 44% and Shigella sonnei for 43% of the isolates. Susceptibility testing showed that 54% were resistant to ampicillin, 72% to trimethoprim-sulfamethoxazole and 77% to tetracycline. Eighty percent were resistant to two or more antimicrobial agents. Morbidity and mortality was higher in children who were initially treated with antimicrobials to which the organism was resistant than in those treated with antimicrobial agent to which the organism was susceptible.
Congenital chloride-losing diarrhea is a recessively inherited disorder due to the absence of chloride-bicarbonate exchange in the small bowel. Malabsorption of chloride leads to osmotic diarrhea, electrolyte abnormalities, and dehydration. If left untreated, the infants fail to thrive and have a very high mortality. Clinically, affected patients develop secretory diarrhea in utero resulting in distended bowel loops and polyhydramnios. At birth these infants have profuse watery diarrhea that may be confused with urine. Thus, the correct diagnosis is often missed, and they may be subjected to unnecessary interventions. If diagnosed early, the electrolyte abnormalities are easily corrected and the prognosis is good. We report two patients who were initially evaluated for other conditions but later proved to have congenital chloride-losing diarrhea. The cases emphasize the importance of having a high index of suspicion in patients with a history of polyhydramnios, prematurity, and watery stools.
Rabbit platelet-rich plasma was incubated with [32P]orthophosphate, after which the platelets were washed, further incubated in the absence or presence of verapamil and subsequently stimulated with PAF-acether or thrombin. In the absence of verapamil, a rapid increase in radioactivity in phosphatidic acid was observed in platelets stimulated with PAF-acether or thrombin. This was inhibited by verapamil over the concentration range 10(-7) to 10(-4) M, at which concentration the rise in phosphatidic acid was completely abolished. In unstimulated platelets, 10(-4) M verapamil induced an increase in radioactivity in polyphosphoinositides but not significantly in phosphatidylinositol. When these verapamil-treated platelets were stimulated with PAF-acether or thrombin, there was a rapid, sustained loss of the additional radioactivity induced in the polyphosphoinositides by verapamil. Polyphosphoinositide radioactivity remained unchanged in platelets stimulated in the absence of verapamil. Verapamil may stimulate formation of a separate pool of polyphosphoinositide which is susceptible to agonist-induced phospholipase C, and failure to re-synthesize this polyphosphoinositide could result from inhibition of phosphatidic acid synthesis.
Treatment with diazinon (40 mg/kg, i.p.) resulted in hyperglycemia and depletion of glycogen from cerebral and peripheral tissues 2 hr after its administration in rats. The activities of the glycogenolytic enzymes glycogen phosphorylase and phosphoglucomutase were increased significantly in brain and liver, whereas that of glucose-6-phosphatase was not altered. The activities of the glycolytic enzymes hexokinase and lactate dehydrogenase were increased only in the brain. The cholinesterase activity of the brain was reduced by treatment with diazinon. The activities of the hepatic gluconeogenic enzymes fructose 1,6-diphosphatase and phosphoenolpyruvate carboxykinase were also increased significantly in diazinon-treated animals. The level of lactate was increased in brain and blood, whereas that of pyruvate was not changed. The activity of glucose-6-phosphate dehydrogenase was not changed significantly. The cholesterol and ascorbic acid contents of adrenals were depleted in diazinon-treated animals. The hyperglycemia and changes in carbohydrate metabolism were abolished by adrenalectomy, suggesting the possible involvement of the adrenals in the induced changes in diazinon-treated animals.
Treatment with diazinon resulted in hyperglycaemia and depletion of glycogen from cerebral and peripheral tissues 2 h after its administration in rats; the changes were maximal after 40 mg/kg diazinon, administered intraperitoneally. The activities of glycogen phosphorylase and phosphoglucomutase were significantly increased in brain and liver, while that of glucose-6-phosphatase was not altered. The activities of the glycolytic enzymes hexokinase and lactate dehydrogenase were increased only in brain. The cholinesterase activity of the brain was reduced by treatment with diazinon. The activities of hepatic gluconeogenic enzymes (fructose 1,6 diphosphatase and phosphoenolpyruvate carboxykinase) were also significantly increased in diazinon-treated animals. The level of lactate was increased in brain and blood while that of pyruvate was not changed. The activity of glucose-6-phosphate dehydrogenase was not significantly changed. Cholesterol and ascorbic acid contents of adrenals were depleted in diazinon-treated animals. Adrenalectomy abolished the hyperglycaemia and changes in carbohydrate metabolism, suggesting the possible involvement of adrenals in the induced changes in diazinon-treated animals.
Explore the source record for details and available documents.
Explore the source record for details and available documents.