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Biomedical subjects

K M Wilson

Publications and source records attributed to K M Wilson.

At least 91 records · Page 5Linked to original sources

Comparison trial of clindamycin with aztreonam or gentamicin in the treatment of postpartum endometritis.

Sixty-two patients who had postpartum endometritis were treated with clindamycin in combination with either aztreonam or the aminoglycoside gentamicin. Currently, the combination of clindamycin and an aminoglycoside constitutes a treatment of choice for this condition. Our results suggest that aztreonam can be substituted for an aminoglycoside in the treatment of postpartum endometritis with similar clinical outcomes.

Adolescent↗

Mineralocorticoids modulate central angiotensin II receptors in rats.

The effect of chronic administration of deoxycorticosterone acetate (DOCA) on the regulation of angiotensin II (AII) receptors in the brains of adult rats was compared with their drinking and pressor responsiveness to both peripheral and central administration of AII. Analysis of AII receptor binding in a block of tissue containing the hypothalamus, thalamus and septum (HTS) after treatment for 8 weeks with DOCA-salt (240 micrograms/kg/day) revealed a significant increase in the number of AII-binding sites compared to salt-loaded controls (Bmax 9.65 vs 6.80 fmol/mg protein) and no change in binding affinity (Kd). Significant increases in the drinking responses to peripheral (200 micrograms/kg) and central (10 ng) administration of AII were observed in these rats. Additional studies indicated that the pressor responses to either centrally (25 ng) or peripherally (20 micrograms/kg, s.c.) administered AII were augmented in DOCA-treated rats. The effect of mineralocorticoids on AII-binding sites was also investigated in primary neuronal cultures from the brains of one-day-old rats. Pretreatment of these cultures with either DOCA or aldosterone (ALDO) induced a time- and concentration-dependent increase in the specific binding of [125I]AII. Maximal increases in AII binding of 53 and 62% above control values were observed when cultures were treated with 500 pg of either ALDO or DOCA per milliliter of culture medium. Scatchard analysis of specific binding of [125I]AII in neuronal cultures treated with DOCA revealed a significant increase in Bmax but no change in Kd. Thus, mineralocorticoid hormones induce an increase in the number of AII-receptor binding sites in the HTS of rats which parallels physiological responses to both central and peripheral administration of AII. This relationship may be independent of the concentration of AII in the blood, since an increase in the number of AII binding sites was also observed in neurons cultured from the brains of one-day-old rats which had been treated with mineralocorticoid hormones.

Aldosterone↗

Effects of radiation on host-tumor interactions using the multicellular tumor spheroid model.

Use of the multicellular tumor spheroid as a tumor model allows separate host or tumor treatment with ionizing radiation and examination of the effects on host-tumor immune interactions. Spheroids of EMT6/Ro, a BALB/c mammary tumor were implanted into the peritoneal cavity of syngeneic immunized mice, recovered, and dissociated into single cells. Cytolytic activity of mature spheroid associated cells and peritoneal cells was resistant to radiation doses as high as 1000 rads when irradiate directly prior to assay. Mice irradiated (200, 400, 700 rads) 24 h prior to spheroid injection had an increased number of tumor cells and decreased number of tumor infiltrating and peritoneal host cells upon spheroid recovery. This was paralleled by an increased colony forming efficiency per spheroid. Cytolytic activity of the spheroid associated cells against radiolabeled EMT6 cells was in many cases decreased with radiation although lysis was the same on a per cell basis. Cytolytic activity by peritoneal cells from these mice increased with dose as measured on a per cell basis. This activity from irradiated animals was carried out by a Thy1+ cell.

Animals↗

Physiologic responses to chronic dietary tyrosine supplementation in DOCA-salt-treated rats.

The antihypertensive effect of chronic administration of L-tyrosine (Tyr) was investigated in a two-part study. In the first experiment, adult male Sprague-Dawley rats were assigned to 1 of 4 treatment groups: control diet plus unilateral nephrectomy (Nphx) and 0.15 M NaCl (Sal) as the sole drinking solution (C-CTRL); control diet plus deoxycorticosterone acetate (DOCA, 268 micrograms/rat/day), Nphx, and Sal (C-DOCA); control diet supplemented with 2.5% L-p-Tyr plus Nphx and Sal (Tyr-CTRL), and Tyr plus DOCA, Nphx, and Sal (Tyr-DOCA). Systolic blood pressure (SBP) increased within 2 weeks after initiation of treatment with DOCA-salt and remained elevated throughout the duration (8 weeks) of the study (p less than 0.001). Dietary administration of Tyr to DOCA-treated rats failed either to affect SBP in normotensive rats or the elevation of SBP in DOCA-treated rats. Dietary supplementation with Tyr induced a significant elevation in urinary excretion of free dopamine (week 1, 3, 5, and 7) and a decreased excretion of free norepinephrine (week 1) without regard to DOCA treatment. Metabolic responsiveness (change in colonic temperature) and cardiovascular responsiveness (change in heart rate) to subcutaneous administration of the beta-adrenergic agonist, isoproterenol, were significantly prolonged while alpha 2-adrenoceptor number (cerebral cortical membranes; 3H-yohimbine binding) was reduced in rats receiving Tyr. In the second experiment, similar rats were assigned to 1 of 3 treatment groups: control diet plus Nphx and Sal, control diet plus Nphx, DOCA and Sal, and Tyr plus DOCA, Nphx, and Sal; however, Tyr was not started until DOCA-salt-induced hypertension developed (4 weeks). Neither acute (2.5 h post-meal) nor chronic (4 weeks) effects of administration of Tyr on SBP were noted. Thus, the Tyr-induced changes observed in these studies include a chronic increase in free dopamine, and a transient decrease in norepinephrine, excretion. No significant effects of Tyr on blood pressure of DOCA-salt-treated rats were observed.

Animals↗

Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats.

Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.

Animals↗

Angiotensin II-induced hypothermia in rats.

Systemic administration of angiotensin II (ANG II) (200 micrograms/kg sc) to the rat induced a hypothermic response that was characterized within 12 min by a reduction in the rate of O2 consumption, vasodilation of the tail, and a 1.3 degrees C fall in colonic temperature. Administration of ANG II in doses ranging from 10 to 200 micrograms/kg resulted in a decrease in colonic and an increase in tail skin temperature. Angiotensin I (ANG I) (200 micrograms/kg sc) induced a similar hypothermic response which was abolished by pretreatment with the ANG I-converting enzyme inhibitor, captopril (35 mg/kg ip). The interaction of ANG II with cholinergic and adrenergic pathways was evaluated to determine possible mechanisms. Treatment with ANG II (200 micrograms/kg sc) and propranolol, a beta-adrenoceptor antagonist (6 mg/kg ip), resulted in a greater depression of colonic temperature (Tco) than was observed with ANG II alone but did not affect the increase in tail skin temperature (Tsk) accompanying administration of ANG II. When ANG II was administered in combination with the beta-adrenergic agonist, isoproterenol (50 micrograms/kg ip), Tco remained at control levels, whereas an enhancement of the ANG II-induced increase in Tsk occurred. Administration of ANG II in combination with atropine sulfate (6 mg/kg ip), a muscarinic receptor antagonist which crosses the blood-brain barrier, significantly reduced the extent of the fall in Tco without affecting the increase in Tsk. The combined treatment of ANG II and the quaternary analogue, atropine methyl nitrate (3.25 mg/kg ip), which does not cross the blood-brain barrier, failed to affect the hypothermic responses to ANG II. These results suggest that the hypothermic responses to ANG II may be mediated through a central cholinergic pathway and possibly influenced by an adrenergic component. The inability of both adrenergic and cholinergic blockers to affect the vasodilatory response of the tail of the rat to administration of ANG II suggests that the mechanisms subserving heat production can be blocked independently of those subserving heat loss.

Angiotensin II↗

The secretory pathway in the mouse epididymis as shown by electron microscope radioautography of principal cells exposed to monensin.

The secretory pathway in principal cells of the mouse epididymis was studied using in vitro labeling and electron microscope radioautography of tissue exposed to the ionophore monensin. After a 5-minute pulse of 3H-leucine, control samples of caput epididymidis were incubated in a modified Krebs-Ringer solution (MKRH medium), while experimental specimens were placed in the same medium, to which 1 microM monensin had been added. At intervals between 5 minutes and 4 hours, samples were fixed and prepared for electron microscope radioautography. Analysis of control specimens revealed heaviest labeling of the rough and the sparsely granulated endoplasmic reticulum early in the experiment followed by a fall in radioactivity, maximal labeling of the Golgi apparatus at 30 minutes, and a pronounced rise in the percentage of grains associated with the apical cell surface and the epididymal lumen beginning 1 hour after administration of precursor. In monensin-treated epididymides, radioactive material accumulated in the Golgi region while the normal increase in labeling of the apical surface and the lumen was completely inhibited for at least 2 hours. The percentage of grains attributed to coated vesicles was also reduced in samples exposed to monensin. In contrast, labeling patterns of the abundant, sparsely granulated, endoplasmic reticulum and the rough endoplasmic reticulum were very similar in monensin-treated and control specimens. The concomitant alterations in labeling of the Golgi apparatus and the lumen demonstrate that the Golgi apparatus participates in intracellular transport of secretory proteins in epididymal principal cells, and is not bypassed as previously suggested. The percentage of grains associated with the sparsely granulated endoplasmic reticulum suggests that much of the synthesis of secretory protein in the principal cells occurs in this organelle, and the lack of alteration of its labeling in the presence of a monensin-induced block at the level of the Golgi apparatus indicates that the sparsely granulated endoplasmic reticulum lies before the Golgi apparatus in the secretory pathway. It is speculated that vesicles play a role in transport of secretory protein from the Golgi apparatus to the lumen.

Animals↗

Drinking: a final common pathway?

Administration of either naloxone, an opioid antagonist (1 mg/kg i.p.), or clonidine, an alpha 2 adrenoceptor agonist (12 micrograms/kg i.p.), attenuated the dipsogenic responses of female rats to both angiotensin II (200 micrograms/kg s.c.) and isoproterenol (25 micrograms/kg s.c.). The effect of simultaneous administration of naloxone and clonidine at these submaximal doses was an additive attenuation of both angiotensin II- and isoproterenol-induced water intakes. The absence of a significant interaction between naloxone and clonidine to inhibit drinking suggests that they act by a similar mechanism. Yohimbine, an alpha 2 adrenoceptor antagonist (300 micrograms/kg i.p.), administered in combination with naloxone, reversed the antidipsogenic effect on angiotensin II-induced drinking. These results provide further support for a role for alpha 2-adrenoceptors in laboratory-induced drinking in rats, and suggest the possibility that the antidipsogenic effect of naloxone is related to alpha 2 adrenergic mechanisms. A model to support these observations is presented in which two separate pathways for the induction of drinking (osmoreceptor- and angiotensin II-induced) converge on a final common pathway. Since both naloxone and clonidine inhibit responses to stimulation of both pathways for drinking, these results suggest that their actions are likely to be at some point as yet undetermined on the final common pathway.

Angiotensin II↗

Limb pterygium syndromes: a review and report of eleven patients.

Conditions with limb pterygia and congenital contractures were reviewed as part of a study of over 350 infants with arthrogryposis. Emphasis was placed on inheritance and variability of distinct pterygium conditions. Eleven patients with limb pterygia were recognized in our study and are described here. Seven of the 350 patients with congenital contractures had the autosomal recessively inherited multiple pterygium syndrome (Patients 1-7). Three of the seven are sibs, a fourth was born to consanguineous parents, and three were chance isolated cases. These seven had multiple joint webs, unusual finger contractures, syndactyly, rocker bottom feet, ptosis, antimongoloid slant of palpebral fissures, epicanthal folds, highly arched palate, scoliosis, and short stature. There is intrafamilial variability. Three patients from one family had a lethal multiple pterygium syndrome. Two were monozygotic twins. They had webbing and contractures of the elbows, knees, neck, and fingers, calcaneovalgus deformity of the feet, and an unusual facial appearance: hypertelorism, flat nose, antimongoloid slant of palpebral fissures, apparently low-set ears. One had a cleft palate. Internal malformations included: bilateral pulmonary hypoplasia, small heart, absence of the appendix, and attenuation of the ascending and transverse colon. One sporadic case of lethal popliteal pterygium with facial clefts was studied. Multiple anomalies included: ankyloblepharon filiforme adnatum, upslanting palpebral fissures, hypoplasia of nasal cartilages, frenula, clefts into the oropharynx lateral to the mouth, apparently low-set ears with slit-like canals, large popliteal pterygia, syndactyly with fusion of all digits in hands and feet, and hypoplastic labia.

Abnormalities, Multiple↗

Assessing interaction between medical trainees and parents of pediatric patients.

The interaction between the health care provider and the parent is recognized as vitally important in the delivery of high quality pediatric care. Attributes of the provider such as empathy, concern for the patient, understanding, and the amount of attention given to the parents' concerns have been found to relate to satisfaction with medical care. Instruments must be developed to assess these attributes in the interaction rather than measuring interviewing technique. The program and research staff of the Child Health Associate Program at the University of Colorado Health Sciences Center modified the Barrett-Lennard Relationship Inventory to evaluate trainees' interaction with parents of patients. This instrument, generally used in psychological settings, has been shown to be a reliable and sensitive tool to measure the perception of patients of the following practitioner qualities in a continual therapeutic relationship: empathic understanding, congruence, and level of regard. In this paper, the authors describe the modification and use of the inventory in acute care medical settings.

Child↗

Rothmund-Thomson syndrome with severe dwarfism.

Two patients had severe dwarfism and limb anomalies, but also had other clinical characteristics of the Rothmund-Thomson syndrome, including characteristic skin changes, abnormal hair growth, sensitivity to sunlight, defective nails and teeth, and juvenile cataracts. We emphasize that this diagnosis should be considered in any patient with extremely short statute, associated skeletal anomalies, and an early onset of typical cutaneous changes.

Adult↗

Maternal and fetal sequelae of anticoagulation during pregnancy.

Review of published cases of pregnancies in which coumarin derivatives or heparin were administered demonstrates that use of either class of anticoagulant carries substantial risks. Of 418 reported pregnancies in which coumarin derivatives were used, one-sixth resulted in abnormal liveborn infants, one-sixth in abortion or stillbirth and, at most, two-thirds in apparently normal infants. In addition to the expected hemorrhagic complications, fetal effects of coumarin derivative administration include a specific embryopathy and central nervous system abnormalities. All available cases (including unpublished ones) of warfarin embryopathy and central nervous system abnormalities following gestational exposure to coumarin derivatives are reviewed, various complications are tabulated, critical periods of teratogenesis are discussed and possible mechanisms proposed. The use of heparin during gestation does not result in a significantly better outcome of pregnancy. In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and, again at most, in two-thirds apparently normal. Because of the substantial risks of both clases of anticoagulants, and the inherent risks of pregnancy complicated by the indications for anticoagulation, prevention of pregnancy is usually indicated. If pregnancy occurs, a relatively normal outcome can be anticipated in about two-thirds of the pregnancies regardless of the anticoagulant used. Heparin does not appear to be a clearly superior alternative to coumarin derivatives.

Abnormalities, Drug-Induced↗

Disposition kinetics and effects of intravenous nicotine.

Nicotine was given intravenously to subjects during acid and alkaline urine conditions in doses and a dosing schedule to simulate cigarette smoking. Total clearances were greater, terminal half-lifes shorter, but volumes of distribution much the same in acid (pH < 5) and alkaline (pH > 7) urine conditions. The effect of urinary pH on total clearance was due entirely to changes in renal clearance, which accounted for 23% and 2% of total clearance in acid and alkaline urine conditions. Nicotine injections induced a sensation of arousal and increased heart rate and blood pressure over the short term, but with repeated injections tolerance to these effects developed rapidly. No differences in subjective or physiologic responses to intravenous nicotine were observed and we consider it unlikely that the effects of smoking a cigarette differ as a function of urinary pH.

Adult↗