Search PubMed⌕ Search

Biomedical subjects

J Neal

Publications and source records attributed to J Neal.

At least 37 records · Page 2Linked to original sources

Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects.

Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S)-warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible for termination of the anticoagulant effect, was most strongly inhibited. Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation. The enhanced anticoagulant effect observed when miconazole and warfarin are coadministered may result from inhibition of P4502C9, the isozyme of P450 primarily responsible for the conversion of (S)-warfarin to (S)-7-hydroxy-warfarin. Because miconazole inhibits a number of P450 isozymes, in addition to P4502C9, it can be expected to lead to interactions with other drugs whose primary metabolism is controlled by these enzymes.

Adult↗

Magnetic resonance appearance of fibromatosis. A report of 14 cases and review of the literature.

We reviewed retrospectively the magnetic resonance (MR) images of 14 soft-tissue lesions of fibromatosis (desmoid tumors) encountered in 11 patients. The lesions were typically inhomogeneous in texture and round to oval in configuration. Margins were well-defined in 78% of the lesions at presentation and were infiltrating in all recurrences. On T1-weighted spin echo MR images, the predominant signal intensity was either isointense or minimally hyperintense when compared with skeletal muscle. On T2-weighted MR images the predominant signal intensity was typically intermediate between skeletal muscle and subcutaneous fat or isointense to fat. Linear and curvilinear areas of decreased signal intensity were distributed throughout the lesions on both pulse sequences in 86% of cases. This pattern strongly suggested fibromatosis. Speculation concerning possible etiologies of this appearance are discussed, and the relevant literature on previously reported cases is reviewed.

Adolescent↗

Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans.

A common pharmacologic approach to lowering elevated serum cholesterol levels has been to interfere with intestinal sterol absorption. Inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) should produce this effect. In this study, we examined the effects of CL 277,082, N-(2,4-difluorophenyl)-N-(4-neopentylbenzyl)-N-(n-heptyl)urea, an ACAT inhibitor, on cholesterol metabolism in humans. Eight healthy male volunteers were given a placebo for 14 days, followed by 750 mg/day CL 277,082 for 20 days in a single-blind, crossover design. Subjects were studied in a hospital research unit and were fed strictly controlled diets. Cholesterol absorption was measured by the dual isotope method during the final week of both the placebo and the drug phases. Sterol balance was also assessed during these two periods by measuring cholesterol intake, and fecal neutral and acidic sterol excretion rates. Plasma lipids and lipoproteins were measured at the end of each period. The drug was well tolerated and produced no detectable clinical or laboratory side effects. Cholesterol absorption, sterol excretion rates, and plasma lipoprotein levels were all unaffected by treatment. We conclude that CL 277,082 may not interfere with ACAT activity or cholesterol absorption in humans at the doses given under the conditions tested in this study.

Adult↗

A comparison of the efficacy and safety of ceftizoxime with doxycycline versus conventional CDC therapies in the treatment of upper genital tract infection with or without a mass.

It is well known that sexually transmitted infections of the upper genital tract are widespread. A variety of regimens are used to treat these conditions, many of which have not been subjected to randomized, prospective clinical trials (including the 1985 Centers for Disease Control [CDC] Guidelines for the treatment of upper genital tract infections [UGTI]). This investigation was undertaken to compare the 1985 CDC treatment guidelines with different doses of ceftizoxime, a third-generation cephalosporin with an intermediate half-life, plus doxycycline in patients with UGTI. The patients were divided into subgroups, depending on the presence or absence of a pelvic mass. Sixty-seven women participated in the study. They were older than 14 years of age and required hospitalization for the treatment of UGTI. These women had lower abdominal pain and tenderness, cervical motion or adnexal tenderness, and one of the following: temperature greater than 100.4 degrees F orally, leukocytosis greater than 10,500/mm3, or presence of a suspected inflammatory pelvic mass on pelvic examination or by ultrasound. Informed consent was obtained from all patients in a manner approved by the Institutional Review Board. Pelvic examinations and ultrasound evaluations of the pelvic soft tissues were performed on all patients at the time of admission. Those who were found not to have a pelvic mass or who had a pelvic mass less than 4 cm in transverse diameter were randomly allocated to receive either ceftizoxime 2 gm intravenously every 12 hours with doxycycline 100 mg intravenously twice daily (Rx 1, n = 13) or cefoxitin 2 gm intravenously every six hours with doxycycline 100 mg intravenously twice daily (Rx 2, n = 14). Those patients found to have a pelvic mass (greater than 4 cm in transverse diameter) were randomly allocated to receive either ceftizoxime 2 gm intravenously every eight hours with doxycycline 100 mg intravenously twice daily (Rx 3, n = 19) or clindamycin 900 mg intravenously every eight hours with a 2-mg/kg loading dose of gentamicin followed by 1.5 mg/kg intravenously every eight hours, with adjustments as necessary (Rx 4, n = 21). All UGTI patients without a mass treated with either Rx 1 or Rx 2 responded adequately. However, UGTI patients with a mass treated with Rx 4 were more likely than those treated with Rx 3 to require a change in antibiotics or need extirpative surgery in order to obtain a satisfactory clinical response (Fisher's exact test = 0.046, two-sided).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Cefmetazole and cefonicid. Comparative efficacy and safety in preventing postoperative infections after vaginal and abdominal hysterectomy.

A single 1-g dose of cefmetazole was compared with a single 1-g dose of cefonicid for prophylaxis in vaginal and abdominal hysterectomy to determine their efficacy and safety. The antibiotics were administered intramuscularly 15-90 minutes before the incision was made. Cefmetazole and cefonicid had similar activity against most of the aerobic organisms recovered, but cefmetazole was significantly more active against anaerobic gram-negative microorganisms. The patterns of regrowth of vaginal flora were similar in the two treatment groups. Patient demographic characteristics and surgical procedures were similar in both groups. The difference in primary prophylactic failure (e.g., cuff cellulitis) with the two study drugs (1 of 53 [1.9%] with cefmetazole and 2 of 28 [7.1%] with cefonicid) did not reach statistical significance, and the results were similar for the two routes of hysterectomy. Cefmetazole, at a dose of 1 g intramuscularly preoperatively, is a safe and effective agent for prophylaxis during hysterectomy.

Adult↗

Focal glomerulosclerosis in Hodgkin's disease necessitating peritoneal dialysis.

A 16-year-old white boy had nephrotic syndrome due to focal segmental glomerulosclerosis six months before the diagnosis of Hodgkin's disease was established. Peritoneal dialysis was necessary for volume control after one month of unsuccessful therapy with high doses of corticosteroids. Nephrosis remitted after two courses of chemotherapy.

Adolescent↗

Surveillance of listeriosis in Los Angeles County, 1985-1986. A first year's report.

After a large food-borne outbreak of listeriosis in Los Angeles County, California, in 1985, the California State Department of Health Services instituted mandatory reporting of Listeria monocytogenes by clinical laboratories. From September 1, 1985, through August 31, 1986, 94 cases of listeriosis were reported in Los Angeles County for an annual crude incidence rate of 12 cases per million persons. Of the 94 cases, 37 (39%) were in neonates and/or their mothers and 57 (61%) were nonperinatal. The overall case fatality rate was 31%, with a perinatal case fatality of 16% (6 fetal and 23 nonperinatal); this compares with an epidemic perinatal case fatality rate of 32%. No significant differences were observed in age-adjusted, race-specific incidence rates among nonperinatal cases or race-specific incidence rates among perinatal cases. All but 2 of the nonperinatal patients had a known predisposing risk factor for the development of listeriosis, the most common of which was a prior history of steroid therapy. A clustering of cases was not identified. No common food sources were apparent. Patients presenting as perinatal cases were more likely to have ingested Mexican-style cheese, ice cream, and yogurt than those presenting as nonperinatal cases. Improved case ascertainment through mandatory reporting and laboratory-based surveillance will establish meaningful baseline levels of listeriosis.

Adolescent↗

Retroperitoneal and pelvic hemangiopericytomas: clinical, radiologic, and pathologic correlation.

Seventeen cases of hemangiopericytoma of the retroperitoneum were retrospectively analyzed for demographic, morphologic, and radiologic features. These tumors were found in all age groups (2 months to 72 years) and occurred in similar numbers of male and female patients. The tumors tended to be large (11 were greater than 8 cm), were well encapsulated, and occurred less frequently in the pelvic retroperitoneal space (six cases) than in abdominal retroperitoneum (11 cases). All tumors were bulky enough to displace part of the gastrointestinal tract, with only two being inoperable. The most distinctive radiologic feature was hypervascularity (found on 11 of 11 angiograms). Other nondiscriminating radiologic features included well-defined margins and necrosis, with nondistinctive amorphous calcification identified in one case. Angiographic or computed tomographic demonstration of hypervascularity in a retroperitoneal tumor is more suggestive of hemangiopericytoma than of a liposarcoma or malignant fibrous histiocytoma, two of the more common tumors of this region.

Adolescent↗

Astrocyte cell lineage. III. The morphology of differentiating mouse astrocytes in colony culture.

Disaggregated cells of newborn DBA/1J mouse neopallium were grown in colony cultures, and colonies of cells at various stages of differentiation along the astrocyte cell lineage were examined after 3 days, 1, 2 and 4 weeks by electron microscopy and by NBD-phallacidin which demonstrates the distribution of microfilaments. The earliest astrocyte precursor cells or glioblasts are closely apposed epithelial cells that rarely have junctions. Their scanty cytoplasm contains many free ribosomes but few microfilaments. The cells in the next stages of astrocyte lineage or proastroblasts are flat and are separated from each other to a variable degree. They have intercellular junctions associated with microfilaments and contain singly dispersed intermediate filaments. The proastroblasts gradually differentiate into astroblasts which have a similar morphology except that in addition to the singly distributed intermediate filaments they also contain intermediate filaments arranged into bundles of various sizes. The mature fibrous astrocytes have well-defined processes and distinct perikarya. They form from astroblasts in culture and also contain numerous bundles of intermediate filaments. The dibutyryl-cyclic AMP (dBcAMP)-induced astrocytes in culture in contrast are large stellate cells similar to reactive astrocytes found around sites of injury in the brain. On the basis of these and previous immunocytochemical studies of the formation and distribution of intermediate filaments in the cytoplasm of differentiating astrocytes, criteria are proposed for identification of different cells along the astrocyte lineage.

Animals↗

Astrocyte cell lineage. II. Mouse fibrous astrocytes and reactive astrocytes in cultures have vimentin- and GFP-containing intermediate filaments.

When cells from mouse neopallium are grown in colony cultures for 10-12 days, small cells with many processes, resembling normal fibrous astrocytes, form on top of the astrocyte precursor cells independently of the presence of dBcAMP in the culture medium. These cells are distinctly different from the much larger, previously described reactive astrocytes which also form in colony cultures and whose maturation is greatly enhanced by the presence of dBcAMP in the culture medium. Immunofluorescence studies showed that both vimentin-containing and glial filament protein (GFP)-containing intermediate filaments (IF) are present in the small normal fibrous astrocytes as well as in the larger reactive astrocytes. The vimentin-containing IF are assembled first in astrocyte precursor cells, whereas GFP-containing IF are assembled later toward the final stages of astrocyte differentiation both in vivo and in vitro. Thus in respect to the expression of the two types of IF, astrocyte differentiation in vitro closely resembles that in vivo. Parallel studies by electron microscopy showed that the vimentin-positive but GFP-negative astrocyte precursor cells contain single IF or small groups of IF, whereas in the more differentiated normal fibrous astrocytes and reactive astrocytes which are also GFP-positive, additional IF arranged in large bundles are present.

Animals↗

Clinical experience with the activated clotting time for the control of heparin and protamine therapy during cardiopulmonary bypass.

The clinical experience with the activated clotting time (ACT) for the control of heparin and protamine therapy during cardiopulmonary bypass in 70 patients (50 adults and 20 children) is reviewed. After a standard dose of 2 mg/kg of body weight of heparin, the patient's ACT ranged from 210 to more than 600 seconds. The heparin dose required to accomplish an ACT of 500 seconds ranged from 1.3 to 4.7 mg/kg for adults and from 2 to 4.5 mg/kg for children. At the termination of bypass, the assessment of the patient's heparin level with the ACT allowed a more accurate reversal with protamine and markedly reduced the protamine requirements. Although the postoperative drainage was not significantly decreased, the total amount of blood transfusion and fresh-frozen plasma and platelet requirements were reduced by 30%, 20%, and 20% respectively. The simple, easy-to-use protocol is presented in detail.

Adult↗