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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 433 records · Page 24Linked to original sources
PubMed1992

Histochemical and morphometric studies of peripheral muscle in bovine progressive degenerative myeloencephalopathy of brown Swiss cattle.

Histochemical and morphometric analysis of selected skeletal muscles was performed on 14 pure bred, Brown Swiss cattle. Nine cattle were clinically affected with bovine progressive degenerative myeloencephalopathy (BPDME) while five served as controls. Statistically significant trend differences were not observed for the parameters of mean cross sectional area, and mean fiber type percentages for types, I, IIA, and IIB fibers between affected and control test groups. In general, patterns of hypertrophy or atrophy, fiber type grouping, fiber type predominance, or fiber cross sectional profile alteration were not observed in the muscles examined from affected cattle. The findings suggest that BPDME, or weaver syndrome, is not a muscular dystrophy and that muscle pathology is not a primary part of the syndrome nor would muscle pathology be expected to contribute significantly to the clinical signs of the disease.

Animals↗
PubMed1992

Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis.

Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.

Audiometry, Evoked Response↗
PubMed1992

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

Alpha-Globulins↗
PubMed1992

New pharmacological approaches to therapy of NIDDM.

Currently available pharmacological agents have not been completely successful in restoring euglycemia in the non-insulin-dependent diabetes mellitus (NIDDM) patient. Several new approaches to the therapy of NIDDM have been formulated in recent years and are in various stages of laboratory or pharmaceutical development. Several of these agents are discussed in this article under categories relating to their mechanisms of lowering blood glucose: 1) inhibition of the release or action of counterregulatory hormones; 2) inhibition of postprandial glucose rise; 3) sensitization of tissues to insulin's actions; and 4) inhibition of gluconeogenesis, including inhibition of the long-chain acyl-CoA-carnitine acyltransferase I, the long-chain acylcarnitine translocase, and pyruvate carboxylase.

Animals↗
PubMed1992

Chronopharmacology of methotrexate pharmacokinetics in childhood leukemia.

Survival has been shown to improve when maintenance therapy for acute lymphocytic leukemia in children is given at night rather during the day. We examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In a crossover study, we determined the pharmacokinetics of intravenous methotrexate at 10:00 and 21:00 h in six children with standard or high-risk leukemia. During the study, children refrained from concomitant drugs (6-mercaptopurine and trimethoprim sulfamethoxazole). There was a significant fall in methotrexate plasma clearance at night (from 5.6 +/- 3 ml/min/kg to 4.7 +/- 2.3 ml/min/kg p < 0.05). Renal clearance of methotrexate tended to decrease at night and unbound renal clearance decreased significantly (from 17.5 +/- 1.7 ml/min/kg to 8.5 +/- 3.6 ml/min/kg p < 0.05). Creatinine clearance did not exhibit diurnal variation, when comparing two 12-h collections, but there was a significant decrease in the nonglomerular clearance of methotrexate (from 14.8 +/- 5.2 to 6 +/- 4 ml/min/kg). Because it is a weak organic acid, the tubular secretion of methotrexate depends on urinary pH. At night urinary pH is more acidic. This may result in more reabsorption and hence reduced renal clearance.

Child↗
PubMed1992

Tinel's sign and Phalen's test in carpal tunnel syndrome.

Tinel's sign and Phalen's test are two provocative tests used in the diagnosis of carpal tunnel syndrome. A review of the literature reveals a wide range of sensitivity for these tests. Analyzing the historical data and comparing these to the Tinel's sign and Phalen's test results of 100 individuals without carpal tunnel syndrome (200 wrists), we conclude that the Tinel's sign is not useful in the evaluation of patients with carpal tunnel syndrome, whereas Phalen's test, which has a greater sensitivity and specificity, can be of use.

Adolescent↗
PubMed1992

Chronic oral etoposide in the treatment of lung cancer.

Etoposide is used commonly to treat both small cell lung cancer and non-small cell lung cancer. It is usually administered intravenously over 3 to 5 consecutive days, and usually given in combination with cisplatin. Preclinical cellular and clinical pharmacokinetic studies have demonstrated that etoposide is schedule-dependent and is optimally administered at low doses over prolonged periods of time. Recent early phase clinical trials have demonstrated that oral etoposide can be administered safely for 14 to 21 consecutive days. This schedule has demonstrated outstanding activity in patients with both recurrent and previously untreated small cell lung cancer. Activity against non-small cell lung cancer has also been reported; response rates are similar to those seen with the most active single agents used in the treatment of the disease. Chronic oral etoposide also has the advantages of outpatient convenience and tolerable side effects. This overview discusses the role of chronic oral etoposide in the management of small cell lung cancer and non-small cell lung cancer. The scientific rationale, results of early phase clinical trials, ongoing research, and future directions regarding the chronic administration of this important antineoplastic drug are also reviewed.

Administration, Oral↗
PubMed1992

Relation of abdominal obesity to hyperinsulinemia and high blood pressure in men.

The relationships between body fatness, adipose tissue distribution, plasma glucose, insulin levels, lipoprotein levels, and resting blood pressure were studied in 81 men aged 36.0 +/- 3.3 years (mean +/- s.d.) (body mass index (BMI): 27.4 +/- 3.8 kg/m2, percentage body fat: 26.4 +/- 6.6%). Systolic and diastolic blood pressures (BP) were significantly associated with the BMI (r = 0.31, r = 0.33, P < 0.01), the waist circumference (r = 0.33, r = 0.27; P < 0.01) as well as with adipose tissue areas measured by computerized tomography (CT) (0.27 < or = r < or = 0.36, P < 0.01). Furthermore, the relative accumulation of subcutaneous abdominal fat, as estimated by the ratio of abdominal to femoral adipose tissue areas measured by CT, was positively correlated with systolic and diastolic BP (P < 0.01). Fasting plasma insulin level (r = 0.30, P < 0.01) as well as the insulin area measured during an oral glucose tolerance test (0.34 < or = r < or = 0.37, P < 0.01) were significantly correlated with blood pressure. Systolic and diastolic BP were significantly associated with HDL2-cholesterol (C) as well as with the HDL2-C/HDL3-C ratio (-0.24 < or = r < or = -0.34), whereas triglycerides (r = 0.23) and the HDL-C/C ratio (r = -0.23) were significantly correlated with diastolic BP only (P < 0.05). Multivariate analysis indicated that the insulin area was the most important variable associated with blood pressure and that this association was independent of total body fatness and regional adipose tissue distribution. Plasma insulin levels explained 14% and 11% of the variance observed in the systolic and diastolic blood pressures respectively. These results suggest that most of the association between abdominal obesity and high blood pressure is mediated by the hyperinsulinemia and/or the related insulin resistant state.

Abdomen↗
PubMed1992

Postoperative respiratory function after laparoscopic cholecystectomy.

Open cholecystectomy causes changes in pulmonary function test volumes; such changes can be related to respiratory complications of hypoxemia and atelectasis. Little data is available on lung volume changes after laparoscopic cholecystectomy. We measured preoperative and postoperative vital capacity (VC), functional residual capacity (FRC), arterial PO2, and chest X-ray atelectasis in 31 patients undergoing laparoscopic cholecystectomy and found small but significant decreases (p < 0.01) in VC (13 +/- 19%) and FRC (7 +/- 17%). The PO2 decreased from 89 +/- 11 mm Hg to 82 +/- 14 mm Hg, with only one patient's PO2 less than 60 mm Hg. Three patients demonstrated new segmental lobar collapse on postoperative chest X-ray. The postoperative changes in FRC (R2 = 0.40, p < 0.04) and atelectasis (R2 = 0.46, p < 0.03) could be predicted by multiple regression of risk factors, including obesity, smoking, use of narcotics, age, and symptoms of prior respiratory disease. We conclude that the respiratory changes after laparoscopic surgery are small in comparison to those expected after open cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed1992

Release of endogenous norepinephrine from rat hypothalamus by stimulation of N-methyl-D-aspartic acid receptors.

Release of endogenous dopamine and norepinephrine (NE) from rat hypothalamic slices superfused with Mg(++)-free medium in the presence of nomifensine and tyrosine was measured by high-performance liquid chromatography coupled to an electrochemical detector. Superfusion with L-glutamic acid or N-methyl-D-aspartic acid elicited a concentration-dependent release of NE but not of dopamine. The release of NE was transient, returning toward basal values despite the continued presence of the amino acid. Superfusion with 20 mM K+ caused a release of NE that declined at a slower rate. Mg++, DL-2-amino-5-phosphonopentanoic acid and MK-801 (D-5-methyl-10,11,dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate), but not 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited the L-glutamic acid-evoked release of NE. The release of NE by L-glutamic acid was virtually abolished by tetrodotoxin and by elimination of Ca++ from and inclusion of 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid in the superfusion medium. Repeated L-glutamic acid applications displayed a decreased response, whereas repeated exposure to 20 mM K+ did not. Exposure to L-glutamic acid in the absence of Ca++ (plus 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) or in the presence of DL-2-amino-5-phosphonopentanoic acid did not reduce the effects seen on subsequent exposure to L-glutamic acid. Exposure to L-glutamic acid in the absence of Mg++ reduced the effect of a subsequent exposure to L-glutamic acid. These observations provide evidence for an indirect modulation of rat hypothalamic endogenous NE by the N-methyl-D-aspartate receptor.

Animals↗
PubMed1992

Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Peroxisomal beta-oxidation of branched chain fatty acids in human skin fibroblasts.

Human skin fibroblasts in suspension are able to degrade [1-14C]-labeled alpha- and gamma-methyl branched chain fatty acids such as pristanic and homophytanic acid. Pristanic acid was converted to propionyl-CoA, whereas homophytanic acid was beta-oxidized to acetyl-CoA. Incubation of skin fibroblasts with [1-14C]-labeled fatty acids for longer periods produced radiolabeled carbon dioxide, presumably by further degradation of acetyl-CoA or propionyl-CoA generated by beta-oxidation. Under the same conditions similar products were produced from very long chain fatty acids, such as lignoceric acid. Inclusion of digitonin (> 10 micrograms/ml) in the incubations strongly inhibited carbon dioxide production but stimulated acetyl-CoA or propionyl-CoA production from fatty acids. ATP, Mg2+, coenzyme A, NAD+ and L-carnitine stimulated acetyl-CoA or propionyl-CoA production from [1-14C]-labeled fatty acids in skin fibroblast suspensions. Branched chain fatty acid beta-oxidation was reduced in peroxisome-deficient cells (Zellweger syndrome and infantile Refsum's disease) but they were beta-oxidized normally in cells from patients with X-linked adrenoleukodystrophy (ALD). Under the same conditions, lignoceric acid beta-oxidation was impaired in the above three peroxisomal disease states. These results provide evidence that branched chain fatty acid, as well as very long chain fatty acid, beta-oxidation occurs only in peroxisomes. As the defect in X-linked ALD is in a peroxisomal fatty acyl-CoA synthetase, which is believed to be specific for very long chain fatty acids, we postulate that different synthetases are involved in the activation of branched chain and very long chain fatty acids in peroxisomes.

Antimycin A↗
PubMed1992

Interactions of endotoxin, prostaglandins, and circulating cells upon pulmonary vascular resistance.

We studied the effects of endotoxin on total pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV) in 24 isolated canine lung lobes. Group 1 lobes were perfused with whole blood; group 2 lobes with granulocyte/platelet depleted blood; group 3 lobes with whole blood and ibuprofen (12.5 mg/kg); group 4 lobes with granulocyte/platelet depleted blood and ibuprofen (12.5 mg/kg). All groups were otherwise treated in a similar manner and all received endotoxin (1 mg/kg) after baseline periods of normoxic and hypoxic ventilation. We found endotoxin increased PVR by 18% in group 1 and by 41% in group 2. Endotoxin administration inhibited HPV in group 1 but did not inhibit HPV in group 2. Ibuprofen administration prevented the increase in PVR and the loss of HPV caused by endotoxin. We conclude that endotoxin administration causes release of a lung-derived vasoconstrictor, but this is obscured by concomitant release of a granulocyte/platelet associated vasodilator. Our data also suggest that granulocytes or platelets may modulate baseline PVR by producing a nonprostaglandin vasodilator.

Animals↗