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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 649 records · Page 36Linked to original sources

Measurement of clonazepam by electron-capture gas-liquid chromatography with application to single-dose pharmacokinetics.

A simple, sensitive, and rapid method for analysis of clonazepam in blood by gas-liquid chromatography with electron-capture detection is described. The method employs neutral benzene extraction from plasma and concentration into a small volume for autoinjection into the electron capture detector-equipped chromatograph. This method consistently provides blank plasma samples free of contaminants in the areas corresponding to the retention times for clonazepam and desmethylflunitrazepam (the internal standard). Sensitivity is 1 ng/mL, and standard curves are linear from 1 to 200 ng/mL. The applicability of the method to single-dose pharmacokinetics is illustrated.

Adult↗

Quantitation of flurazepam and three metabolites by electron capture gas liquid chromatography.

Flurazepam and three of its metabolic products (desalkyl, hydroxyethyl, and aldehyde metabolites) can be simultaneously quantitated without derivatization by gas chromatography with electron capture detection. After addition of a suitable internal standard, unknown biological samples and calibration standards are extracted at neutral pH into benzene/isoamyl alcohol. The reconstituted extract is chromatographed at 275 degrees C with a 10% OV-101 liquid phase, which allows resolution of all 5 compounds. In some cases a 1% OV-225 liquid phase is used for quantitation of hydroxyethylflurazepam. The method is sufficiently sensitive and reproducible for use in clinical and experimental pharmacokinetic studies.

Adult↗

Hepatitis A and B: serologic survey of various population groups.

Seven population groups were tested by radioimmunoassay for the presence of hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Detection of anti-HAV was indicative of past hepatitis A infection and presence of HBsAg or anti-HBs indicated past hepatitis B infection. The results of tests of 680 serum specimens from the seven groups were as follows: (1) of 100 newly admitted children to Willowbrook where hepatitis A and B were hyperendemic, 32% had anti-HAV and 4% had anti-HAV and 4% had HBsAg (1%) plus anti-HBs (3%); (2) of 100 Willowbrook residents who lived in the institution about three or more years, 97% had anti-HAV and 90% had HBsAg (32%) plus anti-HBs (58%); (3) of 100 new Willowbrook employees, 50% had anti-HAV and 13% had anti-HBs; (4) of 100 Willowbrook employees who worked in the institution more than three years, 75% had anti-HAV and 30% had HBsAg (3%) plus anti-HBs (27%); (5) of 80 house staff physicians, 27.5% had anti-HAV and 10% had anti-HBs; (6) of 100 student 34% had anti-HAV and 6% had anti-HBs; and (7) of 100 suburban teenagers 4% had anti-HAV and 5% had anti-HBs. This study confirmed the variability of the prevalence of hepatitis A and B markers among different population groups and the effect of socioeconomic status and environmental factors on the incidence of past infection caused by hepatitis A and B viruses.

Adolescent↗

Epidemic of meningitis and febrile illness in neonates caused by ECHO type 11 virus in Philadelphia.

Between April and November, 1980, an outbreak of meningitis and of febrile illness of neonates caused by ECHO 11 virus occurred in Philadelphia and surrounding communities. Thirty-eight virologically confirmed and ten virologically presumptive cases of meningitis were hospitalized in two Philadelphia hospitals for children. Most patients had fever and irritability. Vomiting, upper respiratory symptoms and poor feeding were present in one-third to one-half of the cases. Seventy-five percent of cases occurred between June 10 and August 18. The number of males and females was similar; 71% of children were 4 months of age or younger. This out break differed from those previously reported on enteroviruses in general, and on ECHO 11 virus in particular, in that no strong male predominance occurred and the patients were younger. A minimum attack rate of 4.1 per 1000 Philadelphia resident children ages 1 day to 4 months was estimated.

Adolescent↗

Paclitaxel for the treatment of progressive or recurrent childhood brain tumors: a pediatric oncology phase II study.

PURPOSE: To assess the efficacy and define the toxicity of paclitaxel given at a dosage of 350 mg/m2 every 3 weeks as a 24-hour continuous infusion to children with recurrent or progressive primary brain tumors. PATIENTS AND METHODS: Seventy-three eligible patients, ages 4 months to 19 years, with progressive or recurrent primary brain tumors were treated according to a Pediatric Oncology Group (POG) phase II protocol with paclitaxel (POG 9330). Tumor histologic strata included: astrocytoma (n = 4), malignant glioma (n = 13), medulloblastoma (n = 16), brain stem glioma (n = 15), ependymoma (n = 13), and miscellaneous histologies (n = 12). All patients had previous histologic confirmation of a primary intracranial or spinal cord tumor with magnetic resonance imaging or computed tomography documentation of unequivocally measurable progressive or recurrent disease. All patients had received previous therapy including surgery, radiation therapy, and/or chemotherapy, but no patient had been previously treated on more than one phase II trial. Paclitaxel was administered as a 24-hour intravenous infusion at a dosage of 350 mg/m2 every 3 weeks. Neurologic and neuroradiologic reevaluations were performed after every second course. Patients were allowed to continue therapy for a total of 18 cycles in the absence of progressive disease or unacceptable toxicity. RESULTS: Seventy-five patients were enrolled onto the POG 9330 protocol; two ineligible patients were removed from the study before receiving any therapy. Of the 73 eligible patients, 72 were evaluable for toxicity and 70 were either fully or partially evaluable for disease response. There was one complete response and three partial responses (5.7%). Twenty patients had stable disease for more than 2 months. Toxicities included mild nausea, central nervous system toxicity, myelosuppression, and febrile neutropenia, including one septic death. One grade 2 and two grade 3 allergic reactions occurred. No cardiac toxicities or arthralgias were reported. CONCLUSION: Paclitaxel is well tolerated in children with recurrent or progressive brain tumors at this dosage and schedule and may result in short-term disease stabilization in this patient population. The lack of a significant number of patients with measurable disease regression, however, precludes it from being identified as an active agent when administered as a single agent by 24-hour continuous infusion.

Adolescent↗

Nitazoxanide, a nitrothiazolide antiparasitic drug, is an anti-Helicobacter pylori agent with anti-vacuolating toxin activity.

Nitazoxanide (NTZ), a synthesized drug of the nitrothiazolide class, was initially developed as an antiparasitic compound. This compound has recently been shown to have antibacterial activities against some bacterial pathogens. In the present study, NTZ and its main metabolite tizoxanide (TIZ) were found to have strong minimum inhibitory concentrations (MICs) against both metronidazole (MTZ)-resistant strains and sensitive clinical isolates of Helicobacter pylori. The MIC90 of both NTZ and TIZ against 37 clinical isolates was 8 microg/ml. Vacuolating toxin activity of H. pylori assayed by HeLa cell vacuole formation was inhibited by NTZ at a sub-MIC. In contrast, urease production by H. pylori was not specifically affected by the sub-MIC of NTZ. An acidic pH (pH 5.0) medium reduced the antimicrobial activity of the drug in terms of growth inhibition due to the low growth rate of the bacteria, but killing activity of NTZ against the bacteria was still observed. Thus, it was apparent that both NTZ and TIZ are highly effective against H. pylori, even when the bacteria are resistant to MTZ.

Anti-Bacterial Agents↗

Electrical stimulation of the conus medullaris in the paraplegic. A 5-year review.

In 1970 we carried out the first electrode implantation of the conus medullaris of a 17-year-old male paraplegic to control the emptying of his paralyzed bladder. Our patient has used electromicturition for 6 years to successfully empty his bladder and prevent urinary infection. To date, a total of 11 paraplegic patients have been implanted (6 males, 5 females). The cause of the paraplegia was the result of trauma, and the implants were performed from 16 days to 15 years postinjury. All the patients had experienced numerous urinary infections and required constant catheter drainage, and it was the opinion of our urologic associate that current methods of control of the bladder problem were of no avail. The bladder was considered to be atonic in 7 patients and spastic in 4. The results indicate that after a follow-up of 1--6 years, 8 patients have complete control of voiding by electrical stimulation (4 female, 4 male). 2 of the males required partial sphincterotomy to improve emptying, but none of the females experienced sphincter interference. One male quadriparetic patient died 7 months postimplantation of pneumonia and hepatitis. There have been no infections related to the implantable device; however, 1 female broke the connecting wires to the spinal cord electrode during a paraplegic basketball game. In addition to the induced electrical contraction of the bladder, we have observed increased autonomic activity below the level of the spinal cord transection, improved defecation, reduction of spasticity in the paralyzed legs, penile erection in males, and reduction of decalcification of the long bones. This group of patients represents the longest use of an implantable electronic device to control bladder function.

Adolescent↗

Hypocarotenemia in patients fed enterally with commercial liquid diets.

We have found that 12 patients requiring permanent enteral feeding secondary to cerebrovascular accident with adequate Vitamin A nutritional status had serum concentrations of various carotenoids which were only 8-17% of sex- and age-matched healthy controls. Their serum retinol levels were normal, but only 61% of their controls despite receiving two to three times the recommended daily allowance (RDA) in retinol equivalents. Commercial enteral formulas were found to contain only negligible quantities of the carotenoids and were the cause of the hypocarotenemia. To assess the ability of these patients to absorb beta-carotene, nine tube-fed patients were given 15 mg of beta-carotene (2.5 times the RDA) in a single dose. Serum concentration time curves showed that only four patients absorbed significant quantities of the beta-carotene and absorption was delayed compared to previously studied subjects taking enteral formulas as meals. These studies suggest that the efficiency of absorption of the fat soluble vitamins may be lower in tube-fed patients and that patients receiving long-term tube feeding are denied the possible protective effects of the carotenoids normally contained in the American diet.

Adult↗

Treatment of acid maltase deficiency with a diet high in branched-chain amino acids.

Acid maltase deficiency in adults is associated with progressive muscle weakness and may effect respiratory muscles resulting in respiratory failure. The biochemical and clinical manifestations of acid maltase deficiency arise from a marked deficiency of the lysosomal enzyme alpha-glucosidase (acid maltase), which normally degrades glycogen to free glucose. In the past few years, high-protein diets have provided an alternative energy source for these patients and resulted in improved muscle strength. Recently, we treated a ventilator-dependent acid maltase-deficient patient with a general diet supplemented with branched-chain amino acids. Branched-chain amino acids are the principal amino acids involved in muscle protein synthesis and utilization. While on this diet, the patient had improvement of respiratory function and muscle strength and was able to be weaned from the ventilator during the day. In addition to his nutritional status, levels of serum branched-chain amino acids, showed improvement within 2 months after the diet started. This diet shows potential advantages over a high-protein diet without supplemented branched-chain amino acids for the treatment of acid maltase deficiency. These include theoretical sparing of amino acids required for muscle protein synthesis by providing higher concentrations of postprandial branched-chain amino acids in the circulation. Also, the liquid formula would be better tolerated by a ventilator-dependent or debilitated patient rather than a high-protein general diet. Further experience with branched-chain amino acid formulas will be needed to substantiate their efficacy in the treatment of acid maltase deficiency.

Adult↗

[Indirect immunofluorescence in endemic pemphigus foliaceus. A contribution to its standardization].

The aim of the present research was to standardize the indirect immunofluorescence reaction for Endemic Pemphigus Foliaceus (Fogo Selvagem). We found that fresh human skin was the ideal substrate and could proceed from foreskin, head, neck, or anterior abdominal wall. PBS pre-washing of the skin preceding the incubation with the serum should be avoided since the antigenicity might be diminished. TAS-calcium pre-serves the Pemphigus antigenic properties of the skin and shall be preferred as the diluent for the sera. Albumin-coated slides are useful because they increase the adherence of the skin sections. The conjugate appropriate dilution is convenientely determined by the radial immunodiffusion test (Ouchterlony method). So far as the correlation between the antibody titer and the clinical activity is concerned, we concluded that a titer of 160 or more was of bad prognosis, since it was associated with the generalized form of the disease or with cases of the localized form refractory to the usual therapy. Nevertheless, this assumption needs confirmation by further studies involving an appropriate clinical approach.

Autoantibodies↗

Pentavalent antimonial nephrotoxicity in the rat.

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Animals↗

Expression of p53 and pRb in bladder and prostate cancers of patients having both cancers.

Evidence has been presented that tumor suppressor genes p53 and Rb play a crucial role in the development of both human prostate and bladder cancer. Patients with either cancer are at an increased risk for developing the other malignancy as compared to the general population. The purpose of the present study was to investigate whether there is abnormal expression of these two suppressor proteins in both the bladder and prostate cancers of the same patient. The expression of p53 and pRb in bladder and prostate cancer specimens obtained from 15 patients having both cancers was studied using immunohistochemical staining with antibodies against these proteins. The expression of p53 and pRb in both bladder and prostate cancers of the same patient was congruent in 8 of 15 cases (53%) for p53 and 9 of 15 cases (60%) for pRb. The significance of these findings warrants further investigations.

Aged↗

MR imaging of the normal and abnormal clivus.

We retrospectively reviewed 330 T1-weighted sagittal images, 80 T2-weighted sagittal images, and 83 gadopentetate-dimeglumine-enhanced scans of normal adults to determine the MR appearance of the normal adult clivus. MR images of 21 patients with an abnormal clivus (19 with tumor invasion and two with marrow reconversion) were also evaluated restrospectively and compared with those of the control group to assess MR features distinguishing the two groups. Our study revealed that a normal adult clivus consisted of low- and high-intensity portions mixed in various proportions on T1-weighted images. The low-intensity portion was isointense or hyperintense relative to the pons and always contained foci of bright signal intensity. The low-intensity tumor of a pathologic clivus tended to be hypointense relative to the pons (17/19), and was completely devoid of foci of bright signal intensity. The normal adult clivus was approximately isointense relative to the pons on T2-weighted images. Clival tumors were grossly hyperintense relative to the pons on T2-weighted images in 11 of 17 patients. In the remaining six patients, either a portion of or the entire lesion was isointense relative to the pons and, therefore, was not detectable on T2-weighted images. A normal adult clivus can enhance to some degree (19/83). Clival tumors were found to enhance intensely. A clivus of very low signal intensity (signal void) on T1- or T2-weighted images was always abnormal. The clivus with marrow reconversion was uniformly hypointense relative to the pons on T1-weighted images and isointense relative to normal marrow on T2-weighted images.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

MR imaging of neuronal migrational disorders.

Neuronal migrational disorders of the brain represent abnormalities in the formation of the neocortex caused by faulty migration of the subependymal neuroblasts. These migrational anomalies include lissencephaly (agyria/pachygyria), pachygyria, schizencephaly, heterotopias, hemimegalencephaly, and polymicrogyria. We used MR imaging (performed on a 0.5-T or 1.5-T scanner) to evaluate 21 patients who had neuronal migratory anomalies. Four patients had lissencephaly, seven had pachygyria, including one patient with hemimegalencephaly, seven had schizencephaly, and three had heterotopias. All MR scans included T1-weighted spin-echo sequences, and seven also had inversion-recovery sequences. The cortical surface, cortex, and gray-white matter interface were well evaluated with both sequences; however, the inversion-recovery images were superior. All but two patients were imaged in both the axial and coronal planes: both projections demonstrated well the migrational abnormalities. MR is an excellent method for diagnosing the migrational anomalies of lissencephaly, pachygyria, schizencephaly, heterotopias, and hemimegalencephaly; it appears to be the imaging method of choice for evaluating these disorders.

Adolescent↗