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Biomedical subjects

K Reed

Publications and source records attributed to K Reed.

At least 37 records · Page 2Linked to original sources

24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone.

Glucocorticoids are commonly prescribed in the post transplant period as a component of combination immunosuppressive regimens. However, the daily 24-hour pattern of helper lymphocytes (CD4+) and suppressor cells (CD8+) during chronic methylprednisolone therapy has not been examined in renal transplant recipients in relation to glucocorticoid exposure and time post-transplant. The response of total lymphocytes, CD4+ and CD8+ lymphocytes was examined in 23 stable renal transplant recipients who received methylprednisolone for at least 8 months post-transplant. The patient's prescribed oral methylprednisolone dose (mean daily dose = 9.7 +/- 2.6 mg) was given intravenously and whole blood was sampled periodically over 24 h for lymphocyte counts and methylprednisolone concentrations. A complete blood count with differential was determined via an automated hemocytometer with CD4+ and CD8+ lymphocytes determined using flow cytometry. Methylprednisolone area under the concentration versus time curve (AUC) was determined and normalized for each patient's respective dose. A general lymphopenia resulted in all patients with a mean decrease of 61 +/- 15% and an average nadir time occurring at 6 h. The decline from baseline was 76 +/- 17% for absolute number of CD4+ and 59 +/- 18% for CD8+ lymphocytes with an average nadir time at 6 h. Twelve patients exhibited a baseline CD4+ count to be less than 688 cells/mm3 (the low end of the reference range) and the lymphocyte count of all the patients fell below this value at the nadir. Six patients had a CD8+ lymphocyte count below 380 cells/mm3 (low end of the reference range) at baseline with 21 of the 23 patients exhibiting less than 380 cells/mm3 at the nadir time. At the time of nadir, the mean CD4+ and CD8+ counts were 156 +/- 105 cells/mm3 and 256 +/- 270 cells/mm3, respectively. In 17 of the 23 patients, the CD4+ count was below 200 cells/mm3 at the time of nadir. The dose-normalized AUC of methylprednisolone ranged from 22.6 to 113.5 ng.h/ml with 48% of patients exhibiting morning cortisol concentrations greater than 60 ng/ml. No correlation was noted between daily methylprednisolone exposure and the extent of lymphocyte decline. Lymphocyte response patterns are not clinically recognized in renal transplant recipients, as a means of monitoring immunosuppression. The absolute CD4+ and CD8+ lymphocyte count and the timing of these sample collections post-steroid administration, may have clinical relevance when serially assessed as is done in other immunologic diseases. Prospective evaluation of lymphocyte subset patterns and correlation with susceptibility to overimmunosuppressive (i.e. opportunistic infections) is necessary to help determine if these complications can be minimized by more individualized steroid dose modification.

Adult

CD4+/CD8+ lymphocyte patterns in renal transplant recipients receiving chronic methylprednisolone.

Circulating lymphocytes play a major role in mediating allograft rejection. The peripheral lymphocyte count is influenced by methylprednisolone administration, however, the relationship of methylprednisolone pharmacokinetics to lymphocyte trafficking patterns and its effect on selected lymphocyte subsets (CD4+, CD8+) in renal transplant recipients receiving chronic, fixed-doses of this glucocorticoid has not been studied. To examine this relationship, seven stable renal transplant recipients were given their usual oral methylprednisolone dose (mean daily dose = 15 mg) intravenously, and whole blood was obtained over 24 hr. CD4+ and CD8+ cells were quantitated with flow cytometry and serum concentrations of methylprednisolone were analyzed by high performance liquid chromatography (HPLC). Following methylprednisolone administration, a lymphocytopenia was noted in all patients with the CD4+ and CD8+ cells declining to less than 75% of baseline with a resultant nadir at 8 hr. The CD4+ and CD8+ count returned to baseline values by 12 to 24 hr in all patients. Interpatient variability in pharmacokinetic parameters of methylprednisolone was noted with a total body clearance of 240 +/- 112 mL/hr/Kg and half-life ranging from 2.2 to 3.9 hr. The variability seen in the clearance and distribution volume of methylprednisolone among these patients suggests that fixed doses result in a variable degree of systemic exposure. The poor correlation between methylprednisolone pharmacokinetic parameters and the decline of CD4+ and CD8+ cells indicates that other factors may play a role in the lymphocyte trafficking response. Nevertheless, nadir CD4+ and CD8+ cell counts may provide a measure of methylprednisolone immunosuppression in transplant recipients. Studies to examine their relationship to clinical outcomes (i.e., graft function, steroid toxicity, opportunistic infections) are currently in progress.

Adult

Acutely psychotic patients receiving high-dose haloperidol therapy.

Despite the trend towards lower neuroleptic dosing in the treatment of psychosis, there continue to be patients who are administered doses that are higher than recommended. Thirty-six acutely psychotic patients receiving parenteral haloperidol were evaluated by the Brief Psychiatric Rating Scale, the Schedule for Affective Disorders and Schizophrenia-Change Version, and the Nurses' Observation Scale for Inpatient Evaluation, as well as by drug levels in plasma. Patients were compared on the basis of total haloperidol dose in the first 24 hours: regular dose (RD: 10-30 mg) and high dose (HD: 40-80 mg). At baseline, patients in the HD group scored significantly higher on the Brief Psychiatric Rating Scale factor Hostile-Suspiciousness and the Nurses' Observation Scale for Inpatient Evaluation factor Irritability. Assignment to regular-dose and HD groups could not be accounted for on the basis of age, gender, weight, or duration of illness. Moreover, drug levels in plasma indicated that the HD patients did not require higher doses on the basis of differences in haloperidol levels.

Acute Disease

Cloning and expression of a rat cardiac delayed rectifier potassium channel.

We have cloned a cDNA (designated RAK) coding for a delayed-rectifier K current (IRAK) from adult rat heart atrium and expressed it in Xenopus oocytes. RAK differs from the cloned rat brain K current, BK2 [McKinnon, D. (1989) J. Biol. Chem. 264, 8230-8236], by one amino acid at residue 411. RAK expressed in oocytes compares closely to the intrinsic adult rat atrial delayed-rectifier current measured by using whole-cell recording of single isolated cells. Northern blot analysis confirmed the presence of the channel in adult rat atrium, and to a lesser extent, in rat ventricle. IRAK activates with time constants ranging from 58 ms at -20 mV to 6 ms at +60 mV and does not show significant inactivation over 800 ms. It is blocked by 4-aminopyridine greater than barium much greater than tetraethylammonium chloride, which is similar to the relative potencies of these blockers on the native delayed rectifier current. We conclude that the main delayed rectifier K current in adult rat atria is virtually identical to a neuronal delayed rectifier, BK2.

4-Aminopyridine

Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial.

A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone.

Administration, Oral

The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse.

Depletion of hepatic glutathione in the mouse by pretreatment with diethyl maleate (DEM) is known to potentiate the acute toxicities of many dimethyl-substituted organothiophosphate insecticides. However, certain studies have raised doubts regarding the participation of glutathione in the detoxification of methyl parathion in the mouse, and hence the putative mechanism of action of DEM-induced potentiation of this insecticide. The present study evaluates the hypothesis that DEM potentiates the acute toxicities of methyl parathion, methyl paraoxon, and fenitrothion by a mechanism other than glutathione depletion. One hour following pretreatment of mice with DEM (0.75 ml/kg i.p.), glutathione was markedly depleted and the acute toxicities of methyl parathion, methyl paraoxon and fenitrothion were potentiated. Administration of glutathione monoethyl ester (20 mmol/kg p.o.) to DEM-pretreated mice attenuated DEM-depletion of hepatic glutathione, or maintained glutathione at or above control levels. However, glutathione monoethyl ester did not alter the DEM-induced potentiation of the lethality of these insecticides. Furthermore, administration of glutathione monoethyl ester to naive mice increased hepatic glutathione levels, but did not affect the percentage of animals succumbing to a challenge dose of methyl parathion, methyl paraoxon, or fenitrothion. These data indicate that DEM potentiates the toxicity of methyl parathion, methyl paraoxon or fenitrothion by a mechanism unrelated to hepatic glutathione content.

Animals

A comparison of adinazolam and desipramine in the treatment of major depression.

Thirty-one patients with a DSM-III (R) diagnosis of Major Depression received adinazolam (n = 16) or desipramine (n = 15) during a 6 week double-blind randomized controlled trial. Both groups showed a significant decline in Hamilton Rating Scale for Depression scores (21.8 +/- 4.5 to 10.7 +/- 8.5 for adinazolam and 23.5 +/- 5.5 to 12.9 +/- 8.6) for desipramine. Melancholic and anxiety symptoms were reduced equally by both drugs. Initial sedation was the most common side-effect with adinazolam. Plasma levels of desipramine and hydroxy-desipramine correlated highly with oral dose after 3 weeks of treatment.

Adult

Measles epidemic: impact on pediatric oncology patients.

Measles, a preventable disease, is again epidemic in the United States and is a threat to the immunocompromised pediatric oncology patient. In response to this latest epidemic, the Immunization Practices Advisory Committee has revised its recommendations for controlling an outbreak and has changed childhood immunization to a two-dose schedule. Full understanding of measles management is needed to effectively protect the pediatric oncology patient during the current epidemic. This article reviews the epidemiology, clinical presentation and management of measles, including recommendations for vaccinations, exposures, isolation, and patient and family education.

Child

Influence of age and parity on the emotional care given to women experiencing miscarriages.

Obstetrical nurses (N = 309) participated in a study of the hypothetical influence of patients' age and parity status on nurses' emotional care for women who had experienced miscarriage. Vignettes in which age and parity were varied were mailed to the sample along with a questionnaire. After factor analysis, three measures of emotional care were used as the dependent variables: emotional seriousness, priority of care, and emotional support. Analysis of variance showed that the parity status of the woman was a significant variable in the nurses' perceptions of emotional seriousness and priority of care, but did not affect the nurses' perceptions of the need for emotional support. Age was not a significant variable in the three measures of emotional care.

Abortion, Spontaneous

Prevalence of neuroleptic-induced dystonia in mania and schizophrenia.

In a prospective study of 41 acutely psychotic patients, neuroleptic-induced dystonic reactions occurred in 62.5% of the manic patients (10 of 16) and 66.7% of the schizophrenic patients (10 of 15), a nonsignificant difference. These findings contradict a recent report suggesting a higher risk for this side effect in mania.

Acute Disease

Leiomyomas of the gastrointestinal tract.

Sixteen patients with leiomyoma of the gastrointestinal tract underwent operation and removal of their tumor during a four- and one-half-year period from January 1980 to July 1984. There were three esophageal, five gastric, two small bowel, four colon, and two anorectal leiomyomas. The majority of gastric leiomyomas presented with bleeding, as did half of the small bowel and colon cases. All were treated by excision without mortality. The various clinical presentations, evaluations, and choice of operative approach for this uncommon tumor are discussed.

Adult

A prospective evaluation of the Port-A-Cath implantable venous access system in chronically ill adults and children.

Totally implantable venous access systems are presently widely used, but large-scale, prolonged studies are lacking in evaluating adequately these systems. We prospectively evaluated 198 systems in 191 patients (ages from two months to 80 years) during a three year period, with a median follow-up time of 330 days (a range of two to 1,088 days). Withdrawal of blood was consistently successful in 91 per cent of the systems. Complication rates for infection and thrombosis were 0.04 and 0.03 per 100 days of catheterization, respectively. No episodes of migration of the catheter or embolization were noted. This was thought to be the result of the placement of all catheters by a cutdown technique rather than percutaneously. Five systems were removed because of thrombosis and 22, because of infection. Implantable venous access devices are reliable and have a low complication rate in adult and pediatric patients who require repetitive venous access.

Adolescent

Changes in plasma catecholamines and plasma renin activity during hypotension in conscious rats with lesions of the nucleus tractus solitarii.

The purpose of the present study was to examine the effects of lesions of the nucleus tractus solitarii on the reflex control of sympathetic activity and renin release in the conscious rat. Two doses of the arteriolar vasodilator hydralazine (0.3 and 1 mg/kg, i.v.) were used to activate reflexively the sympathetic nervous system in nucleus tractus solitarii lesion and control rats. Administration of 1 mg/kg of hydralazine to the control rats caused mean arterial pressure to fall from 120 +/- 2 mm Hg to 84 +/- 2 mm Hg and elicited an 11.2-fold increase in plasma renin activity and a 2.7-fold increase in plasma norepinephrine concentration. Administration of 0.3 mg/kg of hydralazine caused the arterial pressure of the lesion group to fall from 118 +/- 3 mm Hg to a comparable value of 85 +/- 4 mmg Hg, but plasma renin activity and plasma norepinephrine concentration did not rise significantly. However, administration of 1 mg/kg of hydralazine to the lesion group caused arterial pressure to fall from 128 +/- 6 mm Hg to 64 +/- 2 mm Hg, in association with a 12.4-fold increase in plasma renin activity and a 1.6-fold elevation in plasma norepinephrine concentration. Atenolol, a beta 1-adrenoceptor antagonist, blocked 70% of the rise in plasma renin activity caused by 1 mg/kg of hydralazine in both groups of rats. In addition, prior renal denervation also markedly attenuated the rise in plasma renin activity caused by hydralazine in the lesion group. Finally, electrical stimulation of the vagus nerves, which caused a large vasodepressor response in the control group, failed to lower the arterial pressure of the lesion group. Based on these observations, we conclude that in the conscious rat (1) nucleus tractus solitarii lesions eliminate the arterial baroreflexes as well as the cardiopulmonary baroreflex, and (2) severe hypotension induces sympathetically mediated renin release in the apparent absence of arterial and cardiopulmonary baroreflex function.

Animals

Role of radionuclide imaging in the evaluation of wrist pain.

The cause of hand and wrist pain can be difficult to determine, especially when standard radiographs are normal or show only nonspecific changes. This study reports the effectiveness of radionuclide imaging in the evaluation of patients with hand and wrist pain of uncertain cause. Eighty-eight patients with hand and wrist pain and initially normal standard radiographs were evaluated prospectively by additional radiographic methods including the following: routine tomography, wrist arthrography, computerized tomography, or magnetic resonance imaging. Each patient also had bone scintigraphy. The diagnosis established by clinical assessment and by other imaging methods was then compared with the scintigraphic findings. The presence or absence of focal scintigraphic abnormalities correlated with the presence or absence of focal pathology definable by the conventional methods in 88% of patients. As expected, scintigraphy was chiefly of value in defining the locus of an injury or other process in the wrist, rather than the nature of an abnormality. The scintigrams were abnormal in 95% of cases involving complete intrinsic ligament ruptures and fractures and were normal in 96% of patients with no definable injury. Scintigraphic findings correlated poorly with partial intrinsic ligament injuries and in cases of synovitis. Radionuclide imaging is a sensitive means of detecting focal lesions in patients with hand and wrist pain of unknown cause.

Adult