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Biomedical subjects

J W Johnson

Publications and source records attributed to J W Johnson.

At least 73 records · Page 4Linked to original sources

Betamethasone effects on steroid and prostaglandin concentrations in pregnant rhesus monkeys.

Glucocorticoids delay parturition in rhesus monkeys, but the mechanism is unknown. This study was designed to determine the relationship between administration of glucocorticoids and prostaglandin levels in late pregnancy. Pregnant rhesus monkeys received intramuscular betamethasone (2 mg/day) from day 120 to day 133 of pregnancy. 13,14-Dihydro-15-keto-prostaglandin F2 alpha, progesterone, estradiol, estrone, and cortisol in amniotic fluid were measured by radioimmunoassay, and progesterone and estradiol were measured in the maternal serum. Among control animals, between 133 days and 160 days there were significant increases in adrenal size (p less than 0.05) and in amniotic fluid 13,14-Dihydro-15-keto-prostaglandin F2a metabolite, (p less than 0.005), estrone, and progesterone concentrations (p less than 0.05). The increase in adrenal size and the rise in amniotic fluid 13,14-Dihydro-15-keto-prostaglandin F2a metabolite, did not occur in betamethasone-treated monkeys. Maternal serum estradiol levels were suppressed immediately after treatment with betamethasone but recovered to control levels by day 160. Other changes in maternal serum and amniotic fluid sex steroid levels were sought but not observed. These data are consistent with the hypothesis that glucocorticoids delay primate parturition by altering intrauterine prostaglandin F2 alpha metabolism.

Amniotic Fluid↗

Presence of an intracellular endometrial inhibitor of prostaglandin synthesis during early pregnancy in the cow.

Previous studies have detected reduced endometrial secretion of prostaglandins during pregnancy in cattle. The present experiment tested the hypothesis that reduced secretion of prostaglandins is caused by induction of an intracellular endometrial inhibitor of prostaglandin synthesis. The microsomal fraction of parturient bovine cotyledons was utilized as a source of enzymes for prostaglandin synthesis. Endometrial tissues collected at Day 17 of the estrous cycle (n = 12) and pregnancy (n = 12) were homogenized and subjected to differential centrifugation for preparation of microsomes and a high-speed (100,000 x g) cytosolic supernatant. Endometrial intracellular preparations were then examined for the ability to modulate prostaglandin synthesis by cotyledonary microsomes from parturient cows. Endometrial intracellular preparations from cyclic cows decreased (P less than 0.05) PGF synthesis by cotyledonary microsomes to a slight extent (supernatant, 21% reduction; microsomes, 11% reduction), while preparations from pregnant cows markedly decreased (P less than 0.01) PGF synthesis (supernatant, 63% reduction; microsomes, 28% reduction; supernatants vs microsomes, P less than 0.01). Regardless of the amount of arachidonic acid available as substrate (25-400 micrograms) endometrial supernatant from pregnant cows (pooled sample) caused a 50% inhibition (IC50) of prostaglandin synthesis at a tissue equivalent of 270 +/- 9.1 mg. The mechanism of inhibition by endometrial high-speed supernatant from pregnant cows appears to be non-competitive with respect to arachidonic acid. The inhibitor(s) may be proteinaceous (70-75 kDa and 25-35 kDa) and can be precipitated by 20% saturated ammonium sulfate. In conclusion, early pregnancy in cattle appears to be associated with increased amounts of an intracellular endometrial inhibitor of prostaglandin synthesis.

Ammonium Sulfate↗

Patch-clamp recording of amino acid-activated responses in "organotypic" slice cultures.

Patch-clamp recording techniques were used to study the properties of amino acid-activated channels in cultured "organotypic" slices from rat cerebellum and hippocampus. Hippocampal pyramidal cells responded to the three main glutamatergic agonists, N-methyl-D-aspartate (N-Me-D-Asp), quisqualate, and kainate, whereas Purkinje cells responded only to quisqualate and kainate. Analysis of single-channel events recorded in outside-out patches from hippocampal neurons showed large conductance events (50 pS), which occurred more frequently in the presence of glycine. These events could be produced by N-Me-D-Asp and also, at low frequency, by quisqualate. On the other hand, 50-pS events were never observed in Purkinje neurons. This supports the hypothesis that N-Me-D-Asp and "non-N-Me-D-Asp" receptors are distinct molecular entities. Comparison of whole-cell and outside-out patch recordings from Purkinje cells revealed a clear spatial segregation of gamma-aminobutyric acid (GABA) and glutamate receptors: although GABA receptors are found at high density in somatic membrane, quisqualate and kainate receptors are mostly extrasomatic. The results show that organotypic slice cultures are amenable to patch-clamp methods. They also show that, in these cultures, amino acids receptors have specific distribution patterns according to cell type and to region within a cell.

Action Potentials↗

Abdominal rescue after incomplete delivery secondary to large fetal sacrococcygeal teratoma.

Two cases are presented of incomplete vaginal delivery because of fetal sacrococcygeal teratomas. Prompt recognition and aggressive therapy resulted in favorable outcomes with minimal morbidity. The combined vaginal and abdominal manipulations involved repositioning the arms, shoulders, and vertex in the vagina, as the breech was extracted abdominally in a direction opposite to that ordinarily used. While this procedure seemed to work well, it is only applicable when the diagnosis of fetal tumor is made too late to prevent an obstructed delivery. Optimally, obstructed delivery is prevented by early ultrasonographic diagnosis and cesarean delivery before advanced labor.

Adult↗

Treatment of hypertension in pregnancy with methyldopa: a randomized double blind study.

Twenty-five patients whose pregnancies were complicated by chronic hypertension were entered in a double-blind study and randomly allocated to treatment with methyldopa (Aldomet) or placebo. Thirteen patients were in the treatment group and 12 in the placebo group. The two groups showed no significant difference in demographic and pretreatment laboratory profiles. Methyldopa-treated patients registering in the first trimester had a significant reduction in the mean arterial pressure (MAP) during the second and third trimesters (P less than 0.025). No significant differences in birth weight (BW), ponderal index (PI) were found when results were corrected for gestational age (GA), race, and sex. The mean GA was significantly prolonged in the methyldopa-treated group by 10.3 days (P less than 0.05). The frequency of superimposed pre-eclampsia was similar in both groups (33.3% vs. 38.4%). However, 75% of the superimposed pre-eclampsia occurred antepartum in the placebo group, while 80% of the methyldopa-treated group developed superimposed pre-eclampsia intrapartum. The results of this small study suggest that the treatment of hypertension in pregnancy may reduce MAP and possibly delay the occurrence of superimposed pre-eclampsia and thus afford a prolongation of the pregnancy.

Chronic Disease↗

Epidermoid cyst of testis: a case for orchiectomy.

Epidermoid cyst of the testis is a benign lesion without report of metastasis. It cannot be differentiated reliably from the far more common malignant testicular mass on a clinical basis. Simple excision of the cyst, even with concurrent biopsy of the apparently normal surrounding parenchyma, does not exclude the possibility of a remote scar or focus of viable tumor. The existence of a concurrent malignant lesion along with an epidermoid cyst may be more than coincidental. For such an undetected associated lesion, appropriate highly successful adjunctive therapy is delayed if excision of the epidermoid cyst alone is performed. Consequently, inguinal orchiectomy should be the treatment of choice for epidermoid cyst of the testis with the subsequent burden of proof placed on the pathologist to exclude associated lesions that may alter therapy.

Adolescent↗

Predicting the outcome of corticoid therapy for acute ulcerative colitis. Results of a prospective, randomized, double-blind clinical trial.

We looked for factors predicting the therapeutic outcome in 66 patients with severe ulcerative colitis treated with intravenous hydrocortisone or corticotropin (ACTH) for 10 days. Patients were randomized before therapy within strata defined by whether they had received oral corticosteroids continuously before the study (group A, 35 patients) or not (group B, 31 patients). Comparisons were made between groups receiving what we considered optimal corticoid therapy, hydrocortisone for group A and ACTH for group B. Overall, therapeutic success was achieved in 28 (42%), with a median time of 7.5 days. Favorable factors measured on admission to the study were those suggesting less severe colitis activity: absence of fulminant disease, limited disease extent, a shorter duration of the present attack, fewer stools, a lower erythrocyte sedimentation rate (ESR), and a higher hemoglobin. Factors compatible with more severe colitis including fulminant activity, more extensive disease, a shorter total disease duration, bloody stools, and fewer bowel movements, favored an early response among those patients who were to achieve a remission. Prolonging therapy beyond 10 days by switching to the alternate corticoid drug did not improve the remission rate. Achieving remission during the initial therapy period, especially when it occurred early, was the most important predictive factor for a favorable clinical course during the following year. Prolonging therapy did not improve the 1-year remission rate. In fact, a higher proportion of patients who continued to require therapy underwent colectomy than those who received one treatment course.

Acute Disease↗

Nutrition and hydration: relationship to preterm myometrial contractility.

Although the mechanisms responsible for the onset of preterm labor in human pregnancy are unclear, animal studies have demonstrated that decreased nutrient intake is associated with increased uterine prostaglandin F metabolite production and spontaneous uterine contractions. The purpose of this study was to assess the association of maternal nutrition and dehydration with preterm uterine contractility. Pregravid weight-for-height, pregnancy weight gain at 30 weeks' gestation, urine specific gravity, ketonuria, and dependent and generalized edema were measured in 30 women who had preterm uterine contractions and in 30 women matched for race, gestational age, socioeconomic status, and smoking who reported no symptoms of preterm contractility. Data were analyzed with the paired-difference t test, Fisher's exact test, and the Cochran-Mantel-Haenszel test. No statistical association was found for dehydration (high urine specific gravity) and preterm contractility. However, pregravid weight below standard body weight-for-height was statistically associated with preterm contractions (P less than .001), as was low weight gain at 30 weeks' gestation (P = .04). There was an association between preterm contractions and both ketonuria (P less than .0001) and the absence of edema (P = .02). Inexpensive clinical measurements of nutritional status may help to identify women at risk for preterm uterine contractility.

Adolescent↗

Analysis of FMRF-amide effects on Aplysia bursting neurons.

The peptide L-phenylalanyl-L-methionyl-L-arginyl-L-phenylalaninamide (FMRF-amide) was pressure-applied onto the somata of bursting neurons L4 and L6 in the Aplysia abdominal ganglion. FMRF-amide causes a biphasic response, first depolarizing and then hyperpolarizing the neuron. In voltage-clamp experiments, FMRF-amide induces an inward current that begins 100-200 msec after applying the peptide and peaks in 2-10 sec. This is followed by an outward current that begins with a latency of 2-5 sec and peaks in 15-65 sec. The entire response lasts 1-5 min. Experiments were done to separate the two currents induced by FMRF-amide on the basis of ion selectivity and kinetics and to determine their I(V) relationships. The currents were studied using a method to quickly measure I(V) curves. The inward current is caused by a conductance increase and has a reversal potential of approximately +18 mV. This current depends on the concentration of extracellular Na ions but not Ca, Cl, or K ions and is insensitive to tetrodotoxin, hexamethonium, and curare. The outward current is caused by a conductance increase and has a reversal potential of approximately -61 mV, which is similar to the reversal potential of the fast, transient K current (IA) in the same cells. This current is sensitive to changes in the external K ion concentration but not to changes in Cl, Ca, or Na concentration. The outward current is partially blocked by 1 mM 4-aminopyridine but not TEA or curare. Neither current is significantly voltage dependent within the range from -70 to -40 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Slow outward tail currents in molluscan bursting pacemaker neurons: two components differing in temperature sensitivity.

Bursting pacemaker neurons of Tritonia and Aplysia were studied in voltage-clamp experiments to determine the ionic requirements of the slow outward tail current. This current is important for terminating bursts and hyperpolarizing the neuron during the interval between bursts and therefore contributes to the timing of pacemaker activity. A method for rapid extracellular perfusion of the neuron soma with solutions of different ionic composition was used to study the ionic dependence of the tail current. Measurements of the current-voltage relationship were made at different times during the decay of the tail current to determine the reversal potential in different ionic solutions. These experiments showed that 2 or more slow outward currents contribute to the tail current. Temperature had a large effect on these currents. At cold temperatures (10-15 degrees C), the tail current was predominantly a K current. At warm temperatures (20-23 degrees C), both a K current and a K-insensitive outward current were seen. Bursting pacemaker activity occurred throughout this temperature range. Both the K current and the K-insensitive current required Ca influx for activation. These findings help to reconcile conflicting reports in the literature concerning the ionic dependence of the slow outward tail current and suggest a mechanism for temperature compensation of bursting activity in these pacemaker cells.

Action Potentials↗

Amniotic fluid prolactin and fetal lung maturation.

Concentrations of prolactin in amniotic fluid, fetal plasma, and maternal plasma were determined in 34 rhesus monkeys delivered by hysterotomy under general anesthesia at gestational ages of 110 to 160 days (term, 165 days). Included were 15 cases (gestational ages 110 to 143 days) in which the mothers received 2 mg of betamethasone intramuscularly daily for 3 days prior to delivery. Fetal lung maximum volumes were determined in addition to the following indices of fetal lung surfactant: lung alveolar stability, lung phosphatidylcholine concentrations, lung extract surface tensions, and amniotic fluid lecithin to sphingomyelin ratios. Amniotic fluid prolactin was found to correlate significantly with lung alveolar stability (r = 0.51; p less than 0.01), lung phosphatidylcholine (r = 0.51; p less than 0.01), lung extract surface tension (r = -0.39, p less than 0.05) and amniotic fluid lecithin/sphingomyelin ratio (r = 0.50; p less than 0.01). These correlations remained statistically significant even when the effects of gestational age were taken into account. These findings suggest that amniotic fluid may modulate fetal production of surfactant via its prolactin content.

Amniotic Fluid↗

Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis.

Patients with acute myelocytic leukemia and hyperleukocytosis have a poor prognosis due to vascular leukostasis and infiltration in the central nervous system and lungs. The clinical records of all patients with a new diagnosis of acute myelocytic leukemia and initial white blood cell count greater than 100,000 X 10(9)/liter admitted to the Mount Sinai Medical Center between the years 1974 and 1983 were examined. Forty-three patients were identified, 22 of whom had clinical and/or pathologic evidence of leukostasis of the central nervous system and/or lung. All patients received induction chemotherapy with daunorubicin and a continuous infusion of cytosine arabinoside. Thirty-five patients also underwent therapeutic leukapheresis prior to induction chemotherapy. The overall remission induction rate in these 43 patients was 51 percent. Fifteen patients had lung leukostasis; the remission rate for these patients was 27 percent (three complete remissions, one partial remission), as compared with a remission rate of 64 percent (18 of 28) for those without pulmonary leukostasis (chi 21 = 5.53; p = 0.02). Thirteen patients had central nervous system infiltration; the remission rate for these patients was 46 percent (five complete remissions, one partial remission), as compared with 53 percent (16 of 30) for patients without central nervous system involvement (chi 21 = 0.19; p = 0.67). The median survival of 21 patients without leukostasis was 10.8 months, as compared with 15.4 months for seven patients with central nervous system involvement and no lung leukostasis and 0.2 months for 15 patients with pulmonary leukostasis (chi 22 = 19.9; p less than 0.001). Thus, pulmonary leukostasis was found to be the single worst prognostic factor in this group of patients.

Adolescent↗

Fecal alpha 1-antitrypsin measurement: an indicator of Crohn's disease activity.

Random fecal alpha 1-antitrypsin levels were determined in 34 patients, 24 with Crohn's disease, and 10 "controls" having diarrheal illnesses not associated with intestinal protein loss, in an effort to evaluate its usefulness as a measure of Crohn's disease intestinal activity. In the control group, all alpha 1-antitrypsin levels were less than 2 mg/g dry wt of stool. The mean fecal level among those with Crohn's disease was 52.9 mg/g (range less than 2 to greater than or equal to 200). There was a strong correlation between disease activity, as measured by a clinical score, and the alpha 1-antitrypsin levels (Spearman r = 0.65, p = 0.001). This correlation was similarly strong among those with colitis or ileitis. A fecal value greater than 20 mg/g may provide a rough guideline to separate patients with clinically active disease from those with inactive Crohn's disease, despite a considerable range of fecal levels among patients with a particular clinical score. Fecal alpha 1-antitrypsin levels correlated with several other laboratory measures that have been proposed as indicators of Crohn's disease activity. The serum orosomucoid, C-reactive protein, and albumin correlated with the clinical activity score among some of our patient groups. Both clinical scores and laboratory parameters, however, may have limited usefulness in a variety of circumstances. Random fecal alpha 1-antitrypsin determinations seem to provide a reliable, although not directly quantitative, measure of the intestinal activity among patients with Crohn's disease, especially when other methods may be inconclusive.

Adolescent↗

Antepartal uterine hypercontractility secondary to nipple stimulation.

An alarming result was noted in conjunction with a nipple stimulation contraction stress test. In a 42-week pregnant woman with suspected postmaturity, gentle self-stimulation of the right nipple through the clothing for one to 1.5 minutes caused the sudden onset of uterine hypercontractility, increased uterine tone, and severe fetal bradycardia. The bradycardia persisted for approximately five minutes despite supportive measures. Operative delivery was being considered when the fetal heart rate returned to a normal baseline. Ultimately, the patient delivered vaginally without further significant complication. This experience demonstrated that carefully controlled breast stimulation may result in unpredictable uterine hyperstimulation with fetal bradycardia.

Adult↗

Value of umbilical blood acid-base studies in fetal assessment.

Determining umbilical vessel blood gas and acid-base values at delivery is a useful, noninvasive means of assessing the condition of the fetus and of reconstructing intrapartum events. These measurements provide a means of auditing the incidence and severity of fetal acidemia and of evaluating the efficacy of clinical measures of detection and treatment. In addition, these parameters may be useful in differentiating the various causes of fetal acidemia.

Acid-Base Equilibrium↗