Biomedical subjects
Publications and source records attributed to M Hassan.
Seven cases of small, asymptomatic splenic cyst-like lesions (CLL) diagnosed in foetuses and neonates are reported. None of these CLL was operated on; three completely disappeared. Such a complete regression has never been described before. A more conservative app approach to such lesions is suggested in order to prevent the possible complications of inappropriate interventional therapy.
We report our preliminary experience with use of ultrasound in clubfoot and describe our protocol and initial results in the use of this technique.
Melatonin solutions are frequently used in human, animal, and in vitro research. Generally, fresh solutions are prepared, for fear of instability of melatonin in solution. We tested the high-performance liquid chromatography (HPLC) stability of melatonin in aqueous solutions stored room temperature, 4 degrees C, and -70 degrees C for up to 6 months. Solutions were prepared in a laminar flow hood using sterile technique, directly into sterile, pyrogen-free glass vacuum vials for storage. Different concentrations were tested (1.0-113.0 micrograms/ml). There was no loss of potency as assessed by HPLC, and the preparations remained sterile and pyrogen-free. We conclude that melatonin solutions may be prepared in batches maintained in sterile, pyrogen-free vials at 4 degrees C or at -70 degrees C until use within 6 months. This method will save on research time used for preparation of fresh solutions and will reduce the number of dose validation tests for each new experiment.
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Fifty cases of visceral leishmaniasis were admitted in Children's Hospital, Islamabad. Common clinical features were fever (100%), splenomegaly (100%), hepatomegaly (100%), anaemia (96%), abdominal distension (40%), bronchopneumonia (26%) and bleeding diathesis (22%). Hb was below 7.0 G/dl in 80%, white cell count below 4 x 10(9)/cmm in 88% and platelet count below 100 x 10(9)/c4mm in 86%. All the patients showed leishmania donovani bodies in the marrow smears. Fourteen patients were treated with aminosidine (15 mg/kg), intramuscularly daily for 4 weeks. All responded dramatically and none of them went into relapse in a year's follow-up. No side-effects were observed. Aminosidine can therefore, be recommended as a treatment of choice for visceral leishmaniasis in children.
Geographical distribution of thirty-eight cases of visceral leishmaniasis (VL), who were diagnosed in the department of Pathology, Rawalpindi Medical College and two private laboratories in Rawalpindi and Islamabad is presented. Majority (84.2%) came from Azad Kashmir, especially from areas around Poonch (e.g., Rawlakot-28.9%; Bagh-23.7%; Dirkot-5.3% and Pallandari-2.6%) and areas around Muzaffarabad (e.g., Chakothi-13.2% and Punja Sharif-5.3%). Only two patients (5.3%) belonged to Gilgit agency. Four cases came from villages around Murree, Rawalpindi and Abbottabad. These places are not known as endemic areas of VL. It is proposed that epidemiological studies for VL should be carried out in areas of Azad Kashmir, especially concentrating on the places from where patients keep on presenting for treatment in various hospitals of Rawalpindi and Islamabad.
Fourteen patients suffering from dementia of the Alzheimer type were treated with tacrine (tetrahydroaminoacridine, THA) for 1 year in an open trial. Clinical results were evaluated every third month with neuropsychological tests and rating scales. During the dose-finding, two patients were temporarily withdrawn from medication and one patient was excluded because of elevated levels of liver enzymes. With individualized doses the treatment caused few side effects. Plasma levels of THA varied substantially among patients and correlated with elevation of liver enzymes but not with clinical response. Two patients showed a gradual increase in plasma levels of THA despite unchanged doses. Although results of the neuropsychological tests and clinical ratings were mostly negative, the study indicates that THA can be administered safely for prolonged periods of time. Clinical observations and dose-titration strategy in relation to side effects are discussed.
Alopecia is an important long-term complication after bone marrow transplantation (BMT). The aim of this study was to analyze the influence of busulfan concentration on the development of permanent alopecia. Sixty five patients who survived for at least 6 months after BMT were studied. The median follow-up was 2.1 years (range 0.5-5.7 years). Thirty one patients (47%) had some degree of alopecia and 19 of these patients had extensive alopecia. The mean minimum busulfan concentration was 656 +/- 222 ng/ml in patients who developed alopecia compared with 507 +/- 224 ng/ml in those who did not (P = 0.005). Patients with more extensive alopecia had higher busulfan concentrations than patients with less significant abnormalities. In multivariate analysis, alopecia was associated with busulfan concentrations higher than the median (OR 3.43; 95% CI 3.04-3.88), allogeneic transplantation (OR 2.56; 95% CI 2.28-2.88) and female sex (OR 1.96; 95% CI 1.73-2.88). There was no association between alopecia and chronic graft-versus-host disease. High busulfan concentrations may contribute to the development of permanent alopecia and the risk for alopecia should be considered when choosing the conditioning regimen before BMT.
The authors present their experience with the diagnosis and treatment of hyperparathyroidism in a group of eight patients operated between June 1993 and November 1993 at the Surgical Clinic of Dérer's Hospital in Bratislava-Kramáre. They summarize the findings on the disease from the literature and compare them with their own clinical observations, which confirm the indication of surgical revision as a useful localizing method, and the necessity of perioperative histological diagnosis to determine the extent of surgery.
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The pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM-CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM-CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.
Busulfan is widely used as a component of the myeloablative therapy in bone marrow transplantation. Recent studies have shown that the drug disposition is altered in children and is associated with less therapeutic effectiveness, lower toxicities, and higher rates of engraftment failure. We have evaluated the bioavailability of the drug in two groups of patients: eight children between 1.5 and 6 years of age and eight older children and adults between 13 and 60 years. Oral bioavailability showed a large interindividual variation. In children, the bioavailability ranged from 0.22 to 1.20, and for adults, it was within the range 0.47 to 1.03. The elimination half-life after intravenous administration in children (2.46 +/- 0.27 hours; mean +/- SD) did not differ from that obtained for adults (2.61 +/- 0.62 hours). However, busulfan clearance normalized to body weight was significantly higher in children (3.62 +/- 0.78 mL.min-1.kg-1) than that in adults (2.49 +/- 0.52 mL.min-1.kg-1). Also, the distribution volume normalized for body weight was significantly higher in children (0.74 +/- 0.10 L.kg-1) compared with 0.56 +/- 0.10 L. kg-1 in adults. The difference in clearance between children and adults was not statistically significant when normalized to body surface area, which most probably shows that busulfan dosage should be calculated on the basis of surface area rather than body weight. However, to avoid drug-related toxicities, drug monitoring and an individual dose adjustment should be considered because of the variability in busulfan bioavailability.
BACKGROUND: Low birthweight (< 2,500 g) is one of the major predictors of infant mortality. The clinical salience of low birthweight depends on its severity. The impact of smoking on low birthweight is greater in the 1,500-2,499-gm category than below 1,500 gm. This has an important implication for economic analyses of smoking cessation programs for pregnant women. Because health care cost is closely associated with birthweight, the cost of low birthweight attributable to smoking may be different than the average cost of low birthweight for all causes. Little is known about such cost differences. METHODS: The population-attributable risk was used to estimate the number and percentage of low-birthweight infants due to maternal smoking. Costs by birthweight groups were used to determine cost differences between low birthweight due to smoking and for all causes. RESULTS: The net incremental costs per low birthweight due to smoking range from $4,256 to $8,640 compared to the costs of $5,213 to $10,306 per low birthweight by all causes. The cost differences may be up to 18%. CONCLUSION: Considerably lower costs at birth were found in low birthweight due to smoking than for all causes. The cost difference was attributable to the difference in the severity of low birthweight.
An ultrasonographic study of the tongue and the floor of the mouth was performed in 30 healthy children (aged from 1 day to 15 years) in order to assess the normal US anatomy of this region. The scans were performed in sagittal and coronal planes with a 7.5-mHz transducer. Moreover, 22 children (aged from 1 day to 15 years) presenting with various clinical symptoms underwent US examination. This series included infectious and congenital diseases. The US findings were correlated with surgery and pathology in 19 cases, with the clinical follow-up in 2 cases and with the nuclear study in 1 case. In each case, US could anatomically locate the lesion with very good accuracy. We conclude that US of the tongue and the floor of the mouth in children yields overall very good accuracy in the investigation of diseases of this region. In this study, our purpose was (1) to evaluate the normal sonographic anatomy of the tongue and the floor of the mouth in children and (2) to determine whether it was possible to correctly localize various lesions and to evaluate their nature in order to guide the therapeutic approach.
The in vivo distribution of vasoactive intestinal peptide (VIP) was studied for the first time using a rat model in combination with labeled VIP (131I-VIP) and a gamma-camera. A dynamic scan showed that 131I-VIP was cleared rapidly from the blood circulation. The radioactivity was taken up and accumulated in the lungs during the first minute. During the next 15 min, the radioactivity was slowly removed from the lungs and redistributed into the kidneys, gastric mucosa, liver and small intestine. However, the radioactivity extracted by the lungs was about 6-fold lower during the first minute when a large amount of the non iodinated VIP was coinjected with the 131I-VIP. 131I-VIP was eliminated rapidly from the blood with a half-life of 0.44 +/- 0.05 (min +/- SD) while in lung the elimination half-life was determined to 2.3 +/- 0.8 (min +/- SD). Of the radioactivity in the lungs, 2% was found to be intact 131I-VIP after 20 min. In all other organs the radioactivity found was assumed to be low molecular weight fragments of 131I-VIP. We suggest that lungs play an important role to extract VIP from the circulation after an i.v. administration. 131I-VIP degradation products are redistributed mostly to the kidneys and to the gastric mucosa to be excreted through urine and stomach contents, respectively.
Cereal grains and legume seeds, which are key protein sources for the vegetarian diet, are generally deficient in essential amino acids. Maize, in particular, is deficient in lysine. The inherent lack of lysine-rich proteins in maize has necessitated the search for heterologous proteins enriched in this amino acid, the isolation of the corresponding gene and its ultimate introduction into maize through plant transformation techniques. However, a rate-limiting step to this strategy has been the availability of plant-derived lysine-rich proteins. An appealing solution to the problem is to artificially increase the lysine content of a given protein by mutating appropriate residues to lysine. Here, we expound this strategy, starting with the protein alpha-hordothionin that is derived from barley seeds and consists of five lysine residues in a total of 45 amino acids (11% lysine). To facilitate rational substitutions, the 3-D structure of the protein has been determined by homology modeling with crambin. Based on this model, we have identified surface residues amenable to substitution with lysine. Furthermore, the acceptability of the mutations has been validated through the synthesis and characterization of the derivatives. To this end, our approach has permitted the creation of a modified alpha-hordothionin protein that has a lysine content of approximately 27% and retains the antifungal activity of the wild-type protein.
The clinical efficacy of a diluted oral rehydration salts (ORS) solution was compared in a pilot study with that of intravenous (i.v.) therapy and of standard World Health Organization (WHO)/United Nations Childrens Fund (UNICEF) ORS solution in children with acute diarrhea. Sixty-one boys aged 3 to 24 months, admitted to hospital with acute diarrhea and signs of dehydration, were randomly assigned to groups receiving standard ORS solution, diluted ORS solution, or i.v. therapy. In children treated with standard ORS solution and small amounts of plain water, the total fluid intake was 25-39% greater, the stool output was 58-77% greater (p < 0.01), and the duration of diarrhea was 30-55% greater than in the other treatment groups. Intake of plain water, taken separately or added to the ORS solution, was greater in children given diluted ORS solution (73 +/- 23 ml/kg) than in those given standard ORS solution (21 +/- 32 ml/kg) (p < 0.001). The mean serum sodium concentration increased by 2.2 mEq/L in children given standard ORS solution, whereas it decreased by 2.9 mEq/L in those given diluted ORS solution. This study shows that some children develop worsening diarrhea and increasing serum sodium concentrations when treated with standard ORS solution and given only small amounts of plain water. This is probably caused by the slight hypertonicity of standard ORS solution combined with transient partial glucose malabsorption. This can be avoided if water, breast milk, or another low-solute drink is given liberally during maintenance therapy with ORS solution, as recommended by the WHO.
Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of human (h) GH in 23 GH deficiency, 8 Turner's syndrome, and 14 intrauterine growth retardation prepubertal patients. They were evaluated before and 1, 3, 6, and 12 months after the onset of hGH treatment. Seven normal children were followed longitudinally as controls. During hGH treatment, a significant increase in muscle tissue and decrease in adipose tissue cross-sectional areas was observed, leading to a dramatic increase in the muscle/adipose tissue cross-sectional area ratio in each period studied. These findings remained highly significant when corrected for the small variation observed in controls. The body mass index was correlated with muscle and adipose tissue cross-sectional area at each time point (P < 0.0001). The muscle cross-sectional area increment correlated with the first year height velocity (P < 0.01). This study indicates that in children with and without GH deficiency, hGH therapy induces rapid and intense variation of muscle and adipose tissue mass, and that magnetic resonance imaging can be used to study some aspects of the metabolic actions of GH.