Showing papers by "Medical University of South Carolina published in 1991"

Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure

Abstract: Background. Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. Methods. We randomly assigned 1088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with 40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). Results. As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent...

Cystic fibrosis: scoring system with thin-section CT.

Abstract: The progression of lung disease in patients with cystic fibrosis (CF) was evaluated with chest radiography. The severity and extent of the various radiographic changes were scored with the Chrispin or the Birmingham method, which involves the use of imprecise and subjective terms, such as line shadows, large pulmonary shadows, and nodular cystic lesions. Although computed tomography (CT) has been shown to be helpful in the evaluation of lung disease in CF, no scoring system or other objective criteria have been developed for the evaluation of the wide range of pulmonary changes in these patients. A CT scoring system was devised that incorporates all of the changes seen in the lungs of patients with CF. Such a scoring system may facilitate objective evaluation of existing and newly developed therapeutic regimens and may be a valuable tool in the preoperative evaluation of patients being considered for lobectomy or bullectomy and in the selection of patients for lung transplantation.

Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia.

Abstract: In the present study, we examined the possibility that granulosa cell death during ovarian follicular atresia occurs by apoptosis (programmed cell death). To investigate this possibility, atresia was induced in immature female rats by injecting 15 IU PMSG. Controls received either vehicle or no treatment. PMSG-treated animals were killed on days 1-5 post-injection while controls were killed on days 1 or 5. The onset of atresia was assessed histologically by light microscopic inspection of 5 microns tissue sections and functionally by quantification of serum progesterone and estrogen levels. Apoptosis is characterized by the cleavage of genomic DNA into oligonucleosomal length fragments by a Ca2+/Mg(2+)-dependent endogenous endonuclease. Such fragments form a distinctive ladder pattern when separated electrophoretically. Accordingly, the occurrence of apoptosis in granulosa cells was assessed by examining the pattern of fragmented DNA in cell lysates after agarose gel electrophoresis. Gels were stained with ethidium bromide and DNA visualized by UV transillumination. The earliest morphological signs of atresia were detected 4 days after PMSG injection as evidenced by degeneration and detachment of granulosa cells from the basal lamina. Serum estrogen increased from basal to levels 7-fold over controls by day 3 after PMSG treatment, falling to control values by day 4 and thereafter. In contrast, progesterone remained basal for the first 3 days, rising to levels 3-fold and 8-fold above controls 4 and 5 days after PMSG treatment, respectively. Such shifts in the ratio of estrogen to progesterone production are known to be characteristic of follicular atresia. Finally, electrophoretic analysis of low mol wt DNA in granulosa cell lysates revealed a definitive ladder pattern of oligonucleosomal length DNA fragments (characteristic of apoptosis) on days 4 and 5 after PMSG injection. This pattern was not detectable on days 1 and 2 after treatment. Lysates obtained 3 days after PMSG treatment showed a faint apoptotic-like pattern of DNA fragments; a result consistent with other systems in which DNA cleavage begins before any morphological signs of death. Interestingly, a ladder pattern of DNA fragments was present in control lysates suggesting that granulosa cell death under normal (vs. induced) conditions of atresia in immature rats occurs by apoptosis. These data demonstrate an intimate association between apoptotic-like events and dying granulosa cells and thus support the possibility that apoptosis is involved in the induction of follicular atresia.

Clomipramine in the treatment of patients with obsessive-compulsive disorder

Abstract: Two double-blind studies at 21 centers evaluated the therapeutic efficacy, safety, and tolerability of up to 300 mg/d of clomipramine hydrochloride or an equivalent number of placebo capsules in the treatment of 520 patients with obsessive-compulsive disorder, of whom 239 had had the disorder for at least 2 years (study 1) and 281 had been ill for at least 1 year (study 2). On the two principal measures of the severity of the disorder, ie, the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global Obsessive Compulsive Scale, clomipramine was significantly more effective than placebo in both studies. The mean reduction in the Yale-Brown Obsessive Compulsive Scale score at the end of 10 weeks of treatment was 38% and 44% in studies 1 and 2, respectively, for the clomipramine-treated patients and 3% and 5% for the placebo-treated patients. The drug was also found to be superior on the basis of the physicians' and patients' evaluations of global therapeutic change. The most frequently observed adverse effects during clomipramine therapy were those typically associated with tricyclic antidepressant drugs. Although uncommon, the occurrence of seizures and elevated aminotransferase values are potentially serious side effects of clomipramine. Clomipramine was generally well tolerated and was effective in reducing obsessive and compulsive symptoms.

High resolution computed tomography in early scleroderma lung disease.

Abstract: Seventeen patients with early systemic sclerosis (SSc) underwent high resolution computed tomography (HRCT) of the chest to evaluate dyspnea and/or abnormal pulmonary function tests (PFT). All patients were assigned a dyspnea score and each had routine chest radiography (CXR). Bronchoalveolar lavage (BAL) was performed on 10 patients. HRCT was abnormal in 15 patients (88%), while CXR was abnormal in only 10 patients (59%). Mediastinal lymphadenopathy was detected in 7 patients (41%). Disease duration, dyspnea score, and forced vital capacity (FVC) did not correlate with HRCT score. However, trends toward higher total BAL cell counts and higher BAL neutrophil counts were noted in patients with ground glass opacities on HRCT, and BAL lymphocyte counts were significantly higher in such cases. HRCT is superior to CXR for detecting early interstitial lung disease in SSc, but patient history and FVC correlate poorly with HRCT findings. Ground glass opacities on HRCT may reflect active alveolitis, and mediastinal lymphadenopathy associated with SSc lung disease may be a consequence of pulmonary inflammation.

Cocaine-induced psychosis

Abstract: Background Chronic stimulant use can produce a paranoid psychosis that is similar to acute paranoid schizophrenia. While this phenomenon has been systematically explored in amphetamine abusers, it has been relatively unexplored in a systematic fashion in cocaine abusers. Method The experience of cocaine-induced psychosis was evaluated in 55 individuals consecutively admitted for treatment of DSM-III-R cocaine dependence. Each subject was interviewed about their experiences of psychosis while intoxicated by means of a standardized, semistructured interview. Results Fifty-three percent (29/55) of those interviewed reported experiencing transient cocaine-induced psychosis. There was no significant difference in lifetime amount of cocaine use or amount of cocaine use in the month before admission between those who experienced psychosis and those who did not. The psychosis-positive group used significantly more cocaine in the year prior to admission (p less than or equal to .02) and had a longer duration of use (p less than or equal to .01). Males were significantly (p less than or equal to .05) more likely than females to develop psychosis. Ninety percent (26/29) developed paranoid delusions directly related to drug use. Ninety-six percent (28/29) of the subjects experienced hallucinations: 83% (24/29), auditory hallucinations; 38% (11/29), visual hallucinations; and 21% (6/29), tactile hallucinations. Twenty-seven percent (15/55) of subjects developed transient behavioral stereotypies. Conclusion Cocaine-induced paranoia is a common experience among chronic users. Amount and duration of use are related to its development. Implications for a kindling model of cocaine-induced psychosis will be discussed.

Computer-generated physician and patient reminders. Tools to improve population adherence to selected preventive services.

Abstract: Despite an emerging consensus on appropriate preventive services, a minority of patients receive them. A study was undertaken to assess the impact of computer-generated reminders to adult patients, their physicians, or both patients and physicians on adherence to five recommended preventive services: cholesterol measurements, fecal occult blood testing, mammography, Papanicolaou smears, and tetanus immunization. During the academic year 1988-1989, all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups: control, physician reminders, patient reminders, and both physician and patient reminders. Adherence was defined in community-oriented terms: the percentage of patients within each group who had received the preventive service in the recommended interval. During the study period, adherence to four of the five preventive services increased significantly, with the largest increases in the physician and patient reminder group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4% to 35.4% (for each increase, P less than .0001, McNemar's chi-square test). In general, increases were greater in blacks and in patients with any form of insurance coverage. Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings.

Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture.

Abstract: We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage colonies including blast cell colonies in cultures of marrow cells from normal mice. When tested with marrow cells harvested 2 days after injection of 5-fluorouracil at 150 mg/kg, IL-11 enhanced interleukin 3-dependent colony formation, whereas IL-11 alone supported only scant colony formation. Serial observations (mapping studies) of cultures of post-5-fluorouracil spleen cells indicated that the mechanism of the synergistic effect of IL-11 is to shorten the dormant period of stem cells, an effect very similar to that of interleukin 6. When pooled blast cells were plated into medium containing IL-11 and erythropoietin, only macrophage colonies were observed. Thus, IL-11 can directly support the proliferation of committed macrophage progenitors and, and like interleukin 6 and granulocyte colony-stimulating factor, act synergistically with interleukin 3 to shorten the Go period of early progenitors.

Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A gynecologic oncology group study of second‐line therapy in 105 patients

Abstract: One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first-line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty-eight percent of the patients had short-term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).

Mammosomatotropes : presence and functions in normal and neoplastic pituitary tissue.

Abstract: I. Introduction MORE than a half century has passed since Romeis first proposed the “one cell-one hormone” theory which holds that each of the major pituitary hormones is produced by a separate and distinct cell type (1). Consistent with this idea, the acidophilic staining cells (termed acidophils) of the adenohypophysis have been traditionally subdivided into two categories, those that secrete only GH and others that produce just PRL. This view was supported by considerable tinctorial evidence available at the time of Romeis' hypothesis and generated in the subsequent three decades (1–5). Moreover, data produced throughout the 1970s and early 1980s by the use of light microscopic immunocytochemistry (ICC) and immunofluorescence were generally consonant with the one cell-one hormone theory, except in the case of certain pituitary tumors (6–8). The presence of bihormonal acidophils in this latter situation was attributed to aberrant mechanisms attendant to the neoplastic condition. However, as will be disc...

Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia.

Abstract: Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structur...

Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion.

Abstract: Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious.

DAPI as a Useful Stain for Nuclear Quantitation

Abstract: A simple-to-use fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI), visualizes nuclear DNA in both living and fixed cells. DAPI staining was used to determine the number of nuclei and to assess gross cell morphology. Following light microscopic analyses, the stained cells were processed for electron microscopy. Cells stained with DAPI showed no ultrastructural changes compared to the appearance of cells not stained with DAPI. DAPI staining allows multiple use of cells eliminating the need for duplicate samples.

Homicide as a risk factor for PTSD among surviving family members

Abstract: In this National Institute of Justice-funded study, random digit dialing telephone survey methodology was used to screen a large, nationally representative sample (N = 12,500) of the noninstitutionalized U.S. adult population to identify surviving family members and friends of victims of criminal homicide and alcohol-related vehicular homicide. A total of 9.3% of the national sample had lost a family member or friend to homicide. Immediate family survivors (n = 206) completed an interview assessing demographic characteristics and DSM-III-R criteria for homicide-related post-traumatic stress disorder (PTSD). The interview participation rate was 84%. Among immediate family survivors, 23.3% developed PTSD at some point in their lifetimes, and 4.8% met full diagnostic criteria for PTSD during the preceding 6 months. Survivors of criminal and vehicular homicide victims were equally likely to develop PTSD. Survivors who experienced the homicide during their childhood, adolescence, or adulthood also showed equal likelihood of PTSD. Clinical implications of findings are discussed.

Substance Abuse in an Inpatient Psychiatric Sample

Abstract: The relationship between psychoactive drug abuse and psychopathology is complex. There have been few systematic explorations of substance abuse in psychiatric populations since the recent epidemic of cocaine abuse. To update and further explore the relationship between psychiatric illness and substance abuse, 100 consecutively admitted patients to an inpatient psychiatry unit were administered a drug and alcohol use/abuse questionnaire. Sixty-four percent endorsed current or past problems with substance abuse and 29% met DSM-III-R criteria for substance abuse in the 30 days prior to admission. For the major diagnostic categories, there were no significant differences between groups in percentages of patients with substance abuse disorders. There was a trend (p less than or equal to .2) toward an increased number of lifetime psychiatric hospitalizations in the substance-abusing group. Alcohol was the most common drug of choice followed by stimulants, cannabis, and sedative hypnotics. Differences in drug choices between diagnostic categories are discussed. Forty-three percent of urine drug screens obtained were positive, and of those with positive urine drug screens, 42% denied drug use upon admission. Only 40% of patients with current or past substance abuse problems had received treatment for their chemical dependency. In our sample, while substance abuse was very prevalent, it was underreported and undertreated.

An experimental study comparing various anterior capsulectomy techniques

Abstract: • Radial tears at the margin of an anterior capsulectomy may be associated with the exit of at least one loop of an intraocular lens out of the capsular bag ("pea pod" effect) and subsequent decentration. Many ophthalmologists have gained a clinical impression that the anterior capsule is more likely to remain intact if the continuous circular capsulorhexis (CCC) technique is used. However, controlled comparison of the incidence of radial tears with the use of different capsulectomies under standardized conditions has not been performed, to date. In this study, we analyzed the incidence of radial tear formation in 40 human eyes that were obtained post mortem. These eyes were randomized to four technique groups: (1) "can opener," (2) linear capsulotomy, (3) capsulopuncture, and (4) CCC. We demonstrated that the CCC technique is much less likely to cause or be associated with anterior capsular radial tears as opposed to the other three techniques. With the technique of nuclear expression used in this study, radial tears occurred in 100% of cases treated with the can opener, linear capsulotomy, and capsulopuncture techniques, whereas no tears occurred with the CCC technique. This study provides convincing evidence that the CCC is the best available anterior capsulectomy procedure to minimize the incidence of radial tears.

Blood loss in total knee arthroplasty.

Abstract: Over a two-year period, 112 consecutive primary total knee arthroplasties (TKA) were performed according to a standard protocol and were evaluated to determine the effects of intraoperative tourniquet deflation, suction drainage, and immediate continuous passive motion (CPM) on blood loss and the need for blood transfusions. It has been reported that these measures lead to increased morbidity following TKA. The tourniquet was deflated before closure, hemostasis was obtained, and two suction drains were placed for 24 to 48 hours. CPM was started immediately, and continued for a mean of seven days. Serial hematocrits (Hct) were obtained. Mean age of the 64 males and 48 females was 65 years. The diagnosis was osteoarthritis in 86% and rheumatoid arthritis in 14%. Seventy-three percent of the prostheses were cemented and 27% were uncemented. The mean tourniquet time was 104 minutes and the mean length of surgery was 140 minutes. Blood loss measured at surgery averaged 222 ml. Total calculated blood loss averaged 794 ml, but was higher for patients with a cemented versus uncemented prosthesis (p less than .05), and males versus females (p less than .005). It was not related to diagnosis, tourniquet time, or length of surgery. Of the 38% of patients requiring a transfusion (mean, 2.2 units), there was not a significantly greater drop in Hct (from 36.6 to 26.5; change, 10.1) when compared to patients not receiving a transfusion (from 43.1 to 32.5; change, 10.6). Therefore, the need for transfusion was related to preoperative Hct and not the intraoperative or postoperative blood loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy.

Abstract: Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15 +/- 3% versus 31 +/- 2%, p less than 0.05), increased end-diastolic dimension (5.6 +/- 0.8 versus 3.8 +/- 0.2 cm, p less than 0.05), and no change in mass (2.6 +/- 0.1 versus 2.6 +/- 0.2 g/kg, p = NS) compared with controls. Myocyte length significantly increased with SVT (171 +/- 9 versus 109 +/- 11 microns, p less than 0.05), without significant changes in cell width (28 +/- 2 versus 26 +/- 2 microns). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5 +/- 0.8 versus 8.7 +/- 0.8 x 10(-2), p less than 0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72 +/- 3% versus 80 +/- 3% and 45 +/- 5% versus 63 +/- 4%, respectively, p less than 0.05), with no change in total myocyte volume (54.2 +/- 2.7 versus 54.3 +/- 1.8 microns3 x 10(12)). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2 +/- 0.1 cm, p less than 0.05), and LV hypertrophy developed (3.3 +/- 0.3 g/kg, p less than 0.05). Increased myocyte length (158 +/- 5 microns, p less than 0.05) and width (33 +/- 2 microns, p less than 0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5 +/- 2.6 microns3 x 10(12), p less than 0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1 +/- 0.1 versus 4.0 +/- 0.1, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)