Biomedical subjects
Publications and source records attributed to R Patel.
The first prenatal diagnosis of Pallister-Killian syndrome by chorionic villus sampling is presented. Fetal hydrops was noted on ultrasound in early pregnancy, and the karyotype revealed isochromosome 12p mosaicism.
Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.
We show that a phosphatase inhibitor, okadaic acid, induces premature and persistent mitosis during the first cell cycle in sea urchin embryos. Okadaic acid-induced mitosis requires protein synthesis, suggesting that it activates the protein synthesis-requiring mitotic H1 kinase. By microinjecting the calcium chelators BAPTA and EGTA and by measuring Cai using fura-2, an indicator dye, we show that okadaic acid-induced mitosis is independent of the calcium signal that usually triggers mitosis onset in sea urchin embryos. Disabling the calmodulin kinase II that is thought to respond to the mitotic Cai signal using a peptide inhibitor fails to prevent mitosis in response to okadaic acid. These data suggest that okadaic acid bypasses calcium regulation of mitosis by inducing constitutive phosphorylation of a site on the H1 kinase that is normally under the control of the calmodulin-regulated kinase.
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An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)
Hamster sperm DNA is packaged so tightly that it is the most highly condensed eukaryotic DNA known. Nevertheless, the sperm genome is also organized in a very specific fashion by two nuclear structures, the nuclear matrix and the nuclear annulus. The nuclear matrix organizes sperm DNA into loop domains approximately 46 Kb in length by specific attachment sequences. When the sperm nucleus is induced to decondense, the nuclear matrix almost completely dissipates, leaving only the nuclear annulus, a structure located at the implantation fossa within the nucleus. All the DNA remains anchored to the annulus during decondensation. Rotary shadowing transmission electron microscopy of isolated nuclear annuli retaining only a small portion of this anchored DNA suggests that the DNA is anchored to the annulus in a series of mini-loops, 5-10 Kb in length. These data support our previous suggestions that sperm DNA is organized in a very specific manner.
One of the most serious side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is upper gastrointestinal mucosal damage that may result in hemorrhage, perforation, or even death. To determine the association between NSAID ingestion and acute upper gastrointestinal bleeding, we prospectively evaluated all hospitalized patients who underwent upper endoscopy for hematemesis and/or melena over a 12-month period at the Veterans Administration Medical Center of New Orleans and Tulane Medical Center. Forty of the 139 patients (29%) at the Veterans Administration Medical Center and 21 of the 90 patients (23%) at Tulane Medical Center were using NSAIDs at the time of referral for endoscopy. Erosive gastritis was the most common cause of bleeding attributed to NSAIDs (P less than .005). Seventy percent of the patients with acute upper gastrointestinal bleeding who used NSAIDs were over age 55, compared with 55% of patients not using NSAIDs (P less than .05). This study indicates that NSAID use is found in 27% of hospitalized patients presenting with acute upper gastrointestinal bleeding. Future prospective studies are needed to establish whether prophylactic therapy with synthetic prostaglandins may affect the prevalence of upper gastrointestinal bleeding in patients using NSAIDs.
Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation.
We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.
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A survey of Auckland general practitioners was undertaken to explore their use of, and attitudes to, alternative medicines. Three hundred and seventy randomly selected doctors, from a total of about 700 doctors practising in Auckland, were posted questionnaires. Of 249 respondents, 75 (30%) practised one or more forms of alternative medicine. Acupuncture was the therapy most commonly used. Musculoskeletal disorders and chronic pain syndromes were the most frequently treated conditions. A total of 171 (68.7%) respondents referred patients to one or more forms of alternative treatment, and only 56 (32.7%) of these felt it necessary that the person referred to be medically qualified. Younger doctors were more inclined to refer and the most commonly cited reason for referral was failure of conventional medicine.
A community based ophthalmic survey has been carried out in the city of Leicester. Samples of Asians and Caucasians aged 40 years and over were randomly selected from the patients of four general practitioners and invited to have an ophthalmic examination. After adjustment for age, the prevalence rate of age-related cataract was significantly higher in the Asians when compared to the Caucasians. Age-related cataract was found to develop earlier in the Asians. A strict vegetarian diet was found to be a significant risk factor for age-related cataract in the Asian Community in Leicester.
In this study, local and systemic tolerance and pharmacokinetics of trospectomycin sulfate in human beings were evaluated for the first time. Trospectomycin sulfate (U-63,366F; trospectomycin) or sterile saline was administered to 96 healthy male volunteers in doses ranging from 0.25 ml (75 mg) to 3.3 ml (1,000 mg) in a single intramuscular injection in a double-blind, randomized design. Volunteers were screened to establish baseline vital signs and laboratory test values. Pain and tenderness at the injection site, which occurred at doses of 450 mg and above, were the most common side effects; they were mild in severity and transient. Adverse drug experiences reported by subjects included nausea, dizziness, light-headedness, diaphoresis, costal pain, and perioral numbness. The perioral numbness (paresthesia) experienced at doses of 750, 900, and 1,000 mg was probably drug related. No Clostridium difficile toxin was detected in fecal samples. Pharmacokinetic calculations based on data obtained by high-performance liquid chromatography showed that after a 1,000-mg intramuscular dose of trospectomycin (3.3 ml), the serum mean half-life was 1.85 h (1.70 to 2.02 h), mean area under the serum concentration-time curve was 140.2 micrograms.h/ml and was linear with dose, mean peak concentration was 28.3 micrograms/ml (20.4 to 34.7 micrograms/ml), mean time to maximum concentration was 71 min (30 to 120 min), and the elimination rate constant was 0.307 h-1. The elimination rate constant and half-life did not vary with dose. Little trospectomycin was detected in 2-day fecal collections. A few randomly occurring abnormal clinical laboratory test values and vital signs were observed. For the trospectomycin-treated group, creatinine phosphokinase increased substantially for 24 h after injection and then decrease through day 5, while serum glutamic oxalacetic transaminase and lactate dehydrogenase increased slightly.
A total of 311 patients presenting with uncomplicated gonorrhoea were entered into a comparative randomized open-label study and given single-dose treatment with either oral cefuroxime axetil (CAE) or intramuscular procaine penicillin (PP). Neisseria gonorrhoeae was eliminated from 129 (98%) of 131 evaluable patients treated with CAE and 127 (98%) of 129 evaluable patients treated with PP. None of the 4 treatment failures (3 male and 1 female) were caused by beta-lactamase-producing isolates. Both treatments were well tolerated with minor adverse events reported in 3 (2%) of CAE treated patients. We conclude that CAE is an effective, well tolerated treatment for uncomplicated gonorrhoea which has the convenience and acceptability of single-dose oral therapy.
The cell division cycle of the early sea urchin embryo is basic. Nonetheless, it has control points in common with the yeast and mammalian cell cycles, at START, mitosis ENTRY and mitosis EXIT. Progression through each control point in sea urchins is triggered by transient increases in intracellular free calcium. The Cai transients control cell cycle progression by translational and post-translational regulation of the cell cycle control proteins pp34 and cyclin. The START Cai transient leads to phosphorylation of pp34 and cyclin synthesis. The mitosis ENTRY Cai transient triggers cyclin phosphorylation. The motosis EXIT transient causes destruction of phosphorylated cyclin. We compare cell cycle regulation by calcium in sea urchin embryos to cell cycle regulation in other eggs and oocytes and in mammalian cells.
Erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) was tested in 163 cases of senile cataract and 79 age- and sex-matched controls. There was no statistically significant difference between the overall incidence of G-6-PD deficiency in cataract in comparison to controls. However, amongst the cataract patients the frequency of G-6-PD deficiency was significantly higher in the age group 40 to 50 years (12.1%) as compared to those aged 51 years or more.
The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug.
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