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Biomedical subjects

R E Kramer

Publications and source records attributed to R E Kramer.

69 records · Page 4Linked to original sources
PubMed1976

Changes in adrenocortical function in male and female guinea-pigs during maturation.

Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs.

Adrenal Glands↗
PubMed1976

The age-dependent efficacy of polyadenylic-polyuridylic acid therapy upon the development of spontaneous leukemia in AKR mice.

The synthetic double-stranded polynucleotide, polyadenylic-polyuridylic acid, has been shown to increase the long-term survival of AKR mice. In order to determine whether this effect was age dependent, polyadenylic-polyuridylic acid was administered to AKR mice starting at 2, 4, 6, or 8 months of age. The best therapeutic effect was achieved when polyadenylic-polyuridylic acid treatments were begun at 2 months of age, and there was no beneficial effect when begun at 8 months of age.

Age Factors↗
PubMed1976

Mechanism of action of spironolactone on adrenocortical function in guinea pigs.

Spironolactone administration (50 mg/kg/day for 3 days) to make guinea pigs decreased cortisol production by adrenal slices in vitro. Adrenal microsomal and mitochondrial cytochrome P-450 levels were also decreased after treatment with spironolactone. The decline in adrenal cytochrome P-450 content was accompanied by decreases in microsomal 21-hydroxylase and mitochondrial cholesterol side-chain cleavage and 11beta-hydroxylase activities. Activities of other adrenal enzymes, such as delta4-hydrogenase and NADPH-cytochrome c reductase, were unaffected by spironolactone treatment. Cortisone administration to guinea pigs failed to mimic the effects of spironolactone on adrenal function, which indicates specificity of spironolactone action and excludes inhibition of adrenocorticotropin secretion as a mode of action. Addition of spironolactone to isolated adrenal mitochondria or microsomes produced type I spectral changes with spectral dissociation constants similar to those for endogenous steroid substrates. Spironolactone, in vitro, inhibited 11beta- but not 21-hydroxylase activity. The results indicate that spironolactone administration diminishes the activity of adrenal mitochondrial as well as microsomal cytochrome P-450-containing enzymes, resulting in a fall in corticosteroid output.

Adrenal Cortex↗
PubMed1975

Relation of the pituitary gland to gonadal hormone effects on the adrenocortical 11beta-hydroxylase system in rats.

Studies were conducted to further examine the mechanisms responsible for gonadal hormone effects on the rat adrenocortical 11beta-hydroxylase system. Despite higher concentrations of cytochrome P-450 and larger 11-deoxycorticosterone (DOC)-induced difference spectra in adrenal mitochondria from females than males, no sex difference in 11beta-hydroxylase activity was observed. The pregnenolone-induced difference spectrum, indicative of cholesterol binding to cytochrome P-450, also was similar in males and females. Testosterone administration to castrated males lowered both 11beta-hydroxylase activity and mitochondrial cytochrome P-450 content. Estradiol produced the opposite effects in castrated females. However, when given to ACTH-replaced hypophysectomized rats, neither testosterone nor estradiol affected cytochrome P-450 levels or the rate of 11beta-hydroxylation. These observations, taken with the known effects of estradiol and testosterone on ACTH secretion in rats and the effects of ACTH on 11beta-hydroxylation, indicate that gonadal hormone effects on the 11beta-hydroxylase system are mediated by ACTH.

Adrenal Glands↗
PubMed1975

Enhancement of spontaneous C3H/HeJ mammary tumorigenesis by long-term polyadenylic-polyuridylic acid therapy.

Female C3H/HeJ mice received weekly s.c. injections of 2 mg polyadenylic-polyuridylic acid. Therapy was initiated at either 2 or 9 months of age. In both cases, poly-adenylic-polyuridylic acid-treated animals developed the spontaneous mammary carcinoma associated with this strain more rapidly. Because the opposite result was formerly observed for AKR spontaneous leukemia, the data indicate the polyadenylic-polyuridylic acid has no generalized antineoplastic effect upon spontaneous tumors genetically associated with specific murine strains.

Animals↗
PubMedDate not supplied

Effects of single or repeated dermal exposure to methyl parathion on behavior and blood cholinesterase activity in rats.

The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD(50)) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1-3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory.

Administration, Cutaneous↗
PubMedDate not supplied

Growth after intestinal transplant in children.

Intestinal transplantation has been more frequent in children with intestinal failure. However, the growth after intestinal transplantation has not been well documented. The demographics, transplant information, postoperative complications, heights, and weights were obtained retrospectively from medical records on 23 children who underwent intestinal transplantation. Z-scores were calculated from the STAT Growth-BP, based on Centers for Disease Control and Prevention growth chart (2000). Transplantations were performed between 1999 and 2004. Patient median age was 1.1 years (range 0.5 to 6.9 years). Twelve were boys and 11 girls. Seventeen children received multivisceral transplantations, one modified multivisceral transplantation, and five isolated intestinal transplantations. Baseline immunosuppression consisted of tacrolimus and corticosteroids. Daclizumab was used as induction agent in 18 patients; alemtuzumab, in five patients. Median pretransplant Z-scores were median -1.67 (n = 23) in weight, and median -3.36 (n = 21) in height. Pretransplant growth was significantly retarded. We analyzed significantly retarded patients with Z-score <-2.0. The change of weight Z-score from pretransplant was: 1.25 at 6 months (n = 11), 1.46 at 12 months (n = 10), and 2.21 at 24 months (n = 7). The change of height Z-score: 1.9 at 6 months (n = 16), 1.42 at 12 months (n = 13), and 1.51 at 24 months (n = 10). Z-score significantly improved (P < .002, ANOVA). Among the analyzed factors sex, age at transplant, length of stay, and rejection within 6 months, were not associated with catch-up growth. Children with retarded growth showed significant catch-up after successful intestinal transplantation.

Body Height↗
PubMedDate not supplied

Transient focal abnormalities of neuroimaging studies during focal status epilepticus.

We report transient changes in computed tomography (CT) and magnetic resonance imaging (MRI) scans in a patient with focal status epilepticus, referred to us with a tentative diagnosis of neoplasm based on CT and angiographic findings. EEG seizures originated independently from each temporal-occipital area, predominantly from the right. Previous EEGs had shown almost exclusively right temporo-occipital epileptogenic activity. MRI showed increased signal intensity, and CT showed decreased right hemisphere attenuation without enhancement. One month later, there was resolution of the radiological and clinical abnormalities. The transient CT and MRI changes probably represented focal cerebral edema, developing during focal status epilepticus. Lack of change in the left hemisphere probably reflected the quantitative difference in epileptic activity. Clues to the diagnosis of focal edema due to status include: (1) changes on electrical and imaging studies that correlate anatomically with the clinical status, and (2) resolution of abnormalities with appropriate seizure control. In patients with suspected seizure disorders, electrical and clinical data should be correlated before interpretation is made of focal lesions seen by neuroimaging techniques.

Adult↗
PubMedDate not supplied

The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients.

STUDY OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration. DESIGN: Open-label study of intramuscular administration, and double-blind, randomized study of intravenous administration. SETTING: Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively. PATIENTS: Neurosurgical patients who required anticonvulsant prophylaxis or treatment. INTERVENTIONS: In the intramuscular study, 118 patients received loading doses ranging from 480-1500 mg phenytoin equivalents (PE) and daily maintenance doses ranging from 130-1250 mg PE for 3-14 days. In the intravenous study, 88 patients received fosphenytoin and 28 received phenytoin sodium for 3-14 days. Mean +/- SD loading doses and maintenance doses of intravenous fosphenytoin and phenytoin were 1082 +/- 299 mg PE and 411 +/- 221 mg PE, and 1082 +/- 299 mg and 422 +/- 197 mg, respectively. Trough phenytoin concentrations were measured daily in all patients. MEASUREMENTS AND MAIN RESULTS: Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations. Adverse events associated with the drug occurred in 9% of patients, commonly those typical of the parent drug. For intravenous treatment, the frequency of mild irritation at the infusion site was significantly lower in the fosphenytoin group (6%) than in the phenytoin group (25%, p < 0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 micrograms/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. CONCLUSION: Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

Adolescent↗