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Biomedical subjects

D Shaffer

Publications and source records attributed to D Shaffer.

At least 19 recordsLinked to original sources
PubMed1992

Combined kidney and pancreas transplantation. A 3-year experience.

Between May 1988 and September 1991, we performed 26 simultaneous kidney and pancreas transplants and one pancreas transplant after a kidney transplant. All transplants consisted of bladder drainage via a duodenal segment. Actuarial patient, kidney, and pancreas graft survival rates at 12 months were 96%, 88%, and 85%, respectively, and at 24 months were 96%, 88%, and 81%, respectively, and were not significantly different from those of diabetic recipients of cadaver kidney transplants alone. Excellent long-term glycemic control was obtained as monitored by fasting blood glucose and glycosylated hemoglobin levels and by oral glucose tolerance tests. The mean period of hospitalization and number of hospital admissions in the first year posttransplant were significantly greater for patients who received combined kidney and pancreas transplants than for those who received cadaver kidney transplants alone. Combined kidney and pancreas transplants can be performed with patient and graft survival comparable to those of kidney transplants alone, with excellent long-term glycemic control, but result in increased morbidity in the first postoperative year.

Adult↗
PubMed1992

A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days.

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Malignant melanoma in a Hispanic male with nevus of Ota.

Nevus of Ota is uncommon in the non-Oriental population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genitourinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population.

Brain Neoplasms↗
PubMed1992

Bioavailability and patient acceptance of cyclosporine soft gelatin capsules in renal allograft recipients.

OBJECTIVE: To evaluate the relative bioavailability and patient acceptance of cyclosporine (CSA) soft gelatin capsule versus oral solution in renal allograft recipients. DESIGN, SETTING, AND PATIENTS: The bioavailability of CSA capsules was compared with that of CSA solution with crossover study design in the outpatient clinic setting. Nine renal allograft recipients with stable renal function participated in this study. METHODS: CSA dose was switched from solution to capsule in each patient for seven days. At steady-state, nine blood samples were obtained over a 12-hour period from each patient on day 7 for CSA solution and on day 14 for CSA capsules. CSA blood samples were analyzed by HPLC and fluorescence polarization immunoassay (FPIA) methods. Time to peak concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC) were calculated on days 7 and 14, and compared using the matched Student's t-test. Patient acceptance was evaluated by patient preference on the questionnaire. RESULTS: For CSA blood concentrations measured by HPLC assay, the Tmax, Cmax, and AUC were 3.4 +/- 1.3 h, 569 +/- 240 nmol/L, and 4659 +/- 2144 h.nmol/L (mean +/- SD), respectively, with solution and 4.2 +/- 2.1 h, 560 +/- 257 nmol/L, and 4765 +/- 1799 h.nmol/L (mean +/- SD), respectively, with capsules. These differences were not significant (p greater than 0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p greater than 0.1). The mean (+/- SD) relative bioavailability of capsules compared with solution was 109 +/- 29 percent AUC (0-12 h) measured by HPLC and 111 +/- 27 percent AUC (0-12 h) measured by FPIA. All patients expressed preference for capsules over the solution. CONCLUSIONS: CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.

Administration, Oral↗
PubMed1992

Combined liver and whole pancreas procurement in donors with a replaced right hepatic artery.

Aberrant donor arterial anatomy, such as a replaced right hepatic artery, is often considered a contraindication to combined liver and whole pancreas procurement for transplantation. With the increasing interest in transplantation of the pancreas and the demand for cadaver organs, methods for simultaneous procurement despite aberrant donor anatomy are essential. We describe the surgical techniques used successfully in six instances of combined liver and whole pancreas procurement in donors with a replaced right hepatic artery and suggest that a replaced right hepatic artery should not preclude simultaneous procurement in otherwise suitable donors.

Anastomosis, Surgical↗
PubMed1992

Periodic limb movement disorder is associated with normal motor conduction latencies when studied by central magnetic stimulation--successful use of a new technique.

This study prospectively tested the hypothesis that patients with periodic limb movement disorder (PLMD) have longer motor conduction latencies than normals. Six healthy adults, 13 patients with PLMD, and 8 patients with long-term multiple sclerosis (MS) had recordings of motor conduction latencies during wake and sleep. MS subjects were included only to show that we could detect prolongation of central conduction; nonMS subjects were used to test the hypothesis. Subjects had no other medical or sleep problems. A novel magnetic stimulator, the Cadwell MES-10, was discharged over the vertex and the C7 cervical spine. It triggered compound muscle action potentials that were recorded in the abductor digiti minimi in the hand. The conduction latencies were the total conduction time (TCT), measured vertex to hand, and the peripheral conduction time (PCT), measured C7 to hand. The difference was the central conduction time (CCT). Only TCT could be obtained during sleep. Supporting the use of TCT as an indirect measure of central conduction was that, in all waking subjects, TCT correlated with CCT (r = 0.91, p = 0.001) but not with PCT. Reliabilities during wake and sleep were 0.95 or higher for TCT and PCT measurements. Waking CCT was greater in MS subjects (13.77 milliseconds) than those without MS (9.21 milliseconds), p = 0.001. Sleeping TCT was much less impressive in distinguishing MS subjects [27.08 milliseconds in nonrapid eye movement (NREM) sleep; 28.64 milliseconds in rapid eye movement (REM) sleep] from nonMS subjects (24.45 milliseconds in NREM; 24.84 milliseconds for REM), p = 0.07 for NREM and p = 0.04 for REM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Sequential interleukin 2 and interleukin 2 receptor levels distinguish rejection from cyclosporine toxicity in liver allograft recipients.

Previous studies of renal transplant recipients have demonstrated that allograft rejection is accompanied by an increase in plasma and urinary levels of interleukin 2 and its soluble receptor before the development of clinical symptoms. After measuring interleukin 2 and interleukin 2 receptor levels in the plasma, bile, and urine of liver transplant recipients, we found that rejection is preceded by elevation of plasma and biliary levels of both substances, that cyclosporine toxicity did not affect either of these levels, and that urinary levels of the substances are unaffected in either condition. Levels of interleukin 2 and interleukin 2 receptors increased in bile earlier than in plasma, and interleukin 2 levels did not overlap among stable patients and those experiencing rejection, whereas levels of interleukin 2 receptors did. Serial measurements of interleukin 2 levels, particularly in the product of the transplanted organ, provide a reliable assessment of the immunologic status of the allograft.

Bile↗
PubMed1991

Reliability and validity of a psychosocial axis in patients with child psychiatric disorder.

The interrater reliability of a classification scheme of psychosocial stressors was assessed among 52 child psychiatrists in rating exercises with 28 case histories. Validity was evaluated in a field study of 377 cases rated by 39 of the same child psychiatrists. The impact of glossary descriptions on reliability and validity was also determined. Reliability was low with most Kappa values being in the range of 0.20 to 0.40. The glossary did not affect interrater reliability, but it significantly decreased the use of abnormal codes. The discriminant validity of the codes was supported in that the most commonly used codes were used with differential frequency in a pattern that conforms with the known psychosocial correlates of the different psychiatric conditions of childhood.

Child↗
PubMed1991

The impact of curriculum-based suicide prevention programs for teenagers.

The impact of three school-based suicide prevention programs was assessed by comparing attitudes and knowledge of 758 9th and 10th graders with those of 680 control pupils, matched on age, ethnicity, and socioeconomic status at the school level, who did not receive the programs. Evaluations were conducted before exposure to the programs and again 1 month later. A large majority of students knew and subscribed to some of the more important program goals before exposure to the program. There was little evidence of program impact among the minority that did not. Most students were interested by the programs, and positive reactions were more common among female and minority students.

Adolescent↗
PubMed1991

Child psychiatrists' views of DSM-III-R: a survey of usage and opinions.

The DSM-IV Child Psychiatry Work Group surveyed 460 child psychiatrists about their use of DSM-III-R and their reactions to specific proposed nosological revisions for DSM-IV. This paper presents the responses of the sample as a whole and of respondent subgroups with different theoretical, practice, and training characteristics. The survey indicates that DSM-III and DSM-III-R are widely used and generally accepted by child psychiatrists. Ninety-eight percent of respondents believe a criterion-based diagnostic system is useful, and 65% consider DSM-III-R to be an improvement over DSM-III. Depending on the diagnosis 47% to 66% of the respondents reported that they generally assess all applicable criteria and 28% to 49% often refer to the manual before assigning a diagnosis. A majority of respondents supported proposals for several new diagnostic subtypes. Ninety-three percent of respondents indicated that "adequacy of family support" was very valuable for treatment planning or estimating prognosis. Fifty-five percent of respondents admitted to diagnosing adjustment disorders in order to avoid the stigma associated with other disorders. Child psychiatrists who are psychodynamically oriented or practicing in an office-based setting or out of training for more than 10 years tend to use the DSM-III-R less rigorously.

Adolescent↗
PubMed1991

Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration.

Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS.

Animals↗
PubMed1991

Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder.

OBJECTIVE: The authors' objective was to investigate the possibility that glucocorticoid receptor changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD). METHOD: They measured the number of lymphocyte cytosolic glucocorticoid receptors and plasma cortisol concentrations in 15 consecutively admitted male combat Vietnam veterans with PTSD and in a normal comparison group of 11 subjects. RESULTS: Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in glucocorticoid receptor concentrations, paralleling the normal diurnal decline in cortisol levels. The number of glucocorticoid receptors was 63% greater in the morning and 26% greater in the afternoon in the patients with PTSD than in the normal subjects. No group differences in cortisol levels were observed, nor were glucocorticoid receptor number and cortisol levels correlated. The number of morning glucocorticoid receptors was positively correlated with symptoms of PTSD and anxiety. CONCLUSIONS: These results provide further evidence for a dysregulation of the HPA axis in PTSD. The finding that patients with PTSD had a substantially greater number of lymphocyte glucocorticoid receptors than normal comparison subjects is consistent with the authors' previous observations of low 24-hour urinary cortisol excretion in subjects with PTSD. Furthermore, the receptor changes observed are opposite of those reported in major depressive disorder. The present data, along with other findings of HPA abnormalities in PTSD, support the possibility of a greater negative feedback sensitivity at one or more levels of the HPA axis.

Adult↗
PubMed1991

A pilot follow-up study of childhood soft signs and the development of adult psychopathology.

A subgroup of subjects (4 of 12) with childhood soft signs and adolescent anxiety-withdrawal disorders were followed up into adulthood and assessed for soft signs and psychiatric diagnoses. These subjects continued to have soft-sign abnormalities and most had adult anxiety or affective disorders, including obsessive-compulsive disorder (OCD). In contrast, control subjects with childhood soft signs but no adolescent anxiety disorders had fewer soft signs at follow-up and no discrete adult anxiety or affective disorders, but they did have obsessive-compulsive symptoms that did not meet criteria for OCD.

Adolescent↗
PubMed1991

The impact of curriculum-based suicide prevention programs for teenagers: an 18-month follow-up.

In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect.

Adolescent↗