Showing papers by "Medical University of South Carolina published in 1990"

A Comparison of the Efficacy and Safety of a β-Blocker, a Calcium Channel Blocker, and a Converting Enzyme Inhibitor in Hypertensive Blacks

Abstract: A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10—mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs. (Arch Intern Med.1990;150:1707-1713)

Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan.

Abstract: An association between the ingestion tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome. Edema of the extremities, frequently accompanied by pruritus, paresthesia, and myalgia, developed in the nine patients (six women and three men; age range, 30 to 66 years) 1 to 18 months after the start of therapy with tryptophan (1.5 to 3.0 g daily) for insomnia, depression, or obesity. Five patients were taking drugs (benzodiazepines) known to inhibit hypothalamic-pituitary-adrenal function, and one had adrenal insufficiency. All had blood eosinophilia in the acute phase of their illness (mean eosinophil count [+/- SD], 3.62 +/- 2.87 X 10(9) cells per liter). All had histopathological changes in the dermis and subcutaneous tissue typical of scleroderma, and seven patients had eosinophils. The fascia was inflamed and fibrotic, and adjacent skeletal muscle often showed perifascicular inflammation. Tryptophan was discontinued in all patients, and eight received prednisone. The cutaneous symptoms improved, but only two patients had complete resolution of their illness. The patients had plasma levels of tryptophan before and after an oral dose of tryptophan that were similar to those in normal subjects. Plasma levels of L-kynurenine and quinolinic acid, which are metabolites of tryptophan, were significantly higher in four patients with active disease than in three patients studied after eosinophilia had resolved or in five normal subjects (P less than 0.001)--findings consistent with the activation of the enzyme indoleamine-2,3-dioxygenase. This illness resembles eosinophilic fasciitis and probably represents one aspect of the recently reported eosinophilia-myalgia syndrome. The development of the syndrome may result from a confluence of several factors, including the ingestion of tryptophan, exposure to agents that activate indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic-pituitary-adrenal axis.

Changes in Left Ventricular Volume, Mass, and Function During the Development and Regression of Supraventricular Tachycardia-Induced Cardiomyopathy. Disparity Between Recovery of Systolic Versus Diastolic Function

Abstract: Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man. Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined. Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10). Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt]. Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km). Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05). There were no significant changes in Kc or Km. After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.

Development of a crime-related post-traumatic stress disorder scale for women within the symptom checklist-90-revised

Abstract: A community sample of 355 adult women were administered the Symptom Checklist-90-Revised and were assessed with structured interviews for a life-time history of criminal victimization and Crime-Related Post-Traumatic Stress Disorder. Using a criterion group classification approach, a 28-item scale within the SCL-90-R was developed that successfully discriminated between the CR-PTSD positive and negative respondents. Though replication and further research is needed, the developed scale may be of use for initial screening for CR-PTSD as well as for ongoing clinical assessment and research purposes.

Hyperacusis and Otitis Media in Individuals with Williams Syndrome

Abstract: Williams syndrome is characterized by cardiac defects, varying degrees of physical and developmental delay, stellate eye pattern, possible elevated serum calcium level, and elfin/pixie facial featu...

Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine.

Abstract: Chronic supraventricular tachycardia has been associated with ventricular dysfunction in humans and animals. However, this ventricular failure is poorly characterized, and the ultrastructural consequences of supraventricular tachycardia are unknown. We serially examined right and left ventricular function, endomyocardial ultrastructure, and creatine kinase activity in eight pigs at base line and again at 1, 2, and 3 wk following rapid atrial pacing. Left and right ventricular ejection fractions fell significantly from base line after 1 wk of chronic tachycardia. Three weeks of chronic pacing resulted in further deterioration in ejection fractions. Significant biventricular chamber dilatation developed and was associated with a reduction in end-diastolic wall thickness after 2 wk of tachycardia. Mitochondrial injury and diminished mitochondrial cytochrome oxidase staining of subendocardial myocytes were observed after 2 wk of tachycardia. Endomyocardial creatine kinase activity fell from control levels following 2 wk of pacing. Postmortem examination revealed a reduction in left ventricular wall thickness compared with 14 control animals. Fibrosis occurred along the subendocardial layer in paced animals, and glycogen content was also reduced. In summary, chronic supraventricular tachycardia resulted in severe biventricular pump dysfunction and chamber dilatation that were associated with ultrastructural alterations and reduced enzyme activity of the subendocardial myocytes. These ultrastructural and metabolic changes may be potential mechanisms responsible for the ventricular dysfunction and dilatation observed in this model.

The immunoglobulin M heavy chain constant region gene of the channel catfish, Ictalurus punctatus: an unusual mRNA splice pattern produces the membrane form of the molecule

Abstract: The immunoglobulin (IgM) heavy chain constant region gene of the channel catfish, Ictalurus punctatus, has been cloned and characterized. The gene contains four constant region domain-encoding exons (CH1 to CH4) expressed in the secreted form of the immunoglobulin, and two exons encoding the transmembrane (TM) domain utilized in the lymphocyte membrane receptor form of the immunoglobulin. The sequence of a cDNA clone encoding the 3' region of the message for the membrane receptor form of the mu chain indicates that the TM1 exon is spliced directly to the CH3 exon, and not into a site within the CH4 exon, as occurs in the mammals, a shark and an amphibian. This unusual pattern of splicing, which produces a membrane heavy chain that is characteristically smaller than the secreted heavy chain, may be common to all teleost fish.

Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase.

Abstract: Protein catabolic states (i.e., sepsis and trauma) are thought to be associated with accelerated oxidation of branched-chain amino acids (BCAA). Branched-chain alpha-keto acid dehydrogenase (BCKAD), the rate-limiting enzyme for BCAA oxidation by muscle, is regulated by phosphorylation/dephosphorylation. Skeletal muscle BCKAD was only 2-4% active in control rats. Intravenous injection of Salmonella enteritidis endotoxin (0.25-10 mg/kg) did not change total BCKAD activity, but increased the percent active enzyme in muscle three- to four-fold in 4-6 h. Identical results were observed in adrenalectomized rats pretreated with one dose of alpha-methylprednisolone (2.5 mg/kg i.p.) 30-60 min before saline or endotoxin injection, indicating that endotoxin's effect was not mediated by hypersecretion of adrenal hormones. Cortisone pretreatment of normal rats (100 mg/kg per d) for 2 d prevented endotoxin-induced activation of muscle BCKAD, suggesting that endogenous secretion products mediated BCKAD activation by endotoxin. Human recombinant tumor necrosis factor-alpha and/or IL-1 beta or alpha (50 micrograms/kg) increased muscle BCKAD activation two- to fourfold in normal rats 4-6 h after intravenous injection. We conclude that cytokine-mediated activation of muscle BCKAD may contribute to accelerated BCAA oxidation in septicemia.

Microvasculature in systemic sclerosis.

Abstract: The considerable amount of consistent data obtained with different techniques regarding the nailfold capillary morphology and function in SSc sheds increasing light on the natural history and the different evolutive patterns of SSc microangiopathy. These data also provide a strong support for a nosologic spectrum of entities like SSc, CREST syndrome, UCTD and prescleroderma RP. From a practical point of view, a more accurate semiologic analysis of RP should provide interesting clues for the clinical management of patients consulting for that vasomotor disturbance. In the next few years, one can predict that quantitation of the microangiopathy, using morphometry and dynamic videomicroscopy, will increase the usefulness of capillary microscopy in clinical practice for the diagnosis and follow-up of such patients.

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy.

Abstract: From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.

Myocardial stiffness derived from end-systolic wall stress and logarithm of reciprocal of wall thickness. Contractility index independent of ventricular size.

Abstract: The slope of the end-systolic pressure-volume relation (ESPVR) is useful in assessing acute changes in contractile state. However, a limitation of ESPVR is that its slope decreases progressively as ventricular size increases without this change necessarily indicating a change in contractile state. In this respect, an index of contractile function that is independent of ventricular size would have an obvious advantage. The exponential constant (k) of the end-systolic relation between wall stress (sigma) and the natural logarithm of the reciprocal of wall thickness [ln(1/H)], sigma = Cekln(1/H), corresponds to the stiffness constant of the myocardium (kSM), a contractile index that should be independent of ventricular size and geometry. To examine the size independence of kSM, we studied left ventricular kSM during beta-blockade (to stabilize inotropic state) in 25 normal dogs with greatly differing ventricular sizes whose end-diastolic volumes ranged from 14 to 82 ml. The kSM was nearly constant (3.6 +/- 0.4) over this wide range of end-diastolic volumes and thus was independent of end-diastolic volume. Conversely, ESPVR, also obtained during beta-blockade, was closely and negatively correlated to end-diastolic volume (r = 0.92). To test the ability of kSM to measure changes in contractile state, we altered contractile state pharmacologically. The kSM increased from 3.7 +/- 0.5 to 4.8 +/- 0.8 (p less than 0.01) with infusion of dobutamine (after reversal of beta-blockade) and decreased to 3.1 +/- 0.3 (p less than 0.05) with inhalation of isoflurane, a negative inotrope, during beta-blockade (p less than 0.05). We conclude that kSM is independent of ventricular size and is sensitive to changes in inotropic state. As such, it should be useful as an index of contractile function.

Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury.

Abstract: Activation of arachidonic acid occurs after spinal cord injury. Leukotriene B4 is a lipoxygenase metabolite of arachidonic acid. In a rat model of experimental spinal cord injury, we found that the leukotriene B4 content was less than the sensitivity of our assay (8 pg/mg of protein) in non-traumatized spinal cord. Leukotriene B4 was detectable in traumatized cord (mean +/- SE, 25 +/- 5 pg/mg of protein; n = 3). Release of leukotriene B4 from spinal cord slices into the incubation medium was also noted after trauma (9 +/- 1 pg/mg of protein; n = 12) and was enhanced by exposure of traumatized spinal cord slices to the calcium ionophore A23187 (375 +/- 43 pg/mg of protein; n = 12). The amount of leukotriene B4 released corresponded to the extent of post-traumatic polymorphonuclear cell infiltration determined by a myeloperoxidase assay. Results from this study suggest that the source of leukotriene B4 in spinal cord injury is infiltrating polymorphonuclear cells.

Clinical pharmacokinetics of imipramine and desipramine.

Abstract: The pharmacokinetics of imipramine and desipramine have been extensively investigated with recent studies designed to understand sources of intersubject variability and to study discrete clinical populations rather than healthy volunteers. Sources of intersubject variability in pharmacokinetics are both genetic (oxidative phenotype) and environmental. Oxidative phenotype has an important impact on first-pass metabolism. In individuals with poor metabolism, systemic availability for imipramine is increased. Intrinsic clearance of desipramine is reduced 4-fold in individuals with poor metabolism. Recent pharmacokinetic studies in diverse patient populations such as the depressed elderly, children and alcoholics have revealed decreased clearance of imipramine in the elderly and increased clearance of both imipramine and desipramine in chronic alcoholics. In at least a third of the population, nonlinear pharmacokinetics of desipramine may be observed at steady-state plasma concentrations above 150 micrograms/L. These nonlinear changes in desipramine pharmacokinetics are not associated with age or sex, but are associated with higher desipramine 2-hydroxydesipramine concentration ratios. Hydroxylated metabolites of imipramine and desipramine may possess both antidepressants and cardiotoxic activity but their formation is rate limited and plasma concentrations tend to follow the parent compound with little accumulation. The potent cardiovascular effects of the hydroxymetabolites may be particularly relevant for the elderly and in acute overdose.

Observations on the Elastic Behavior of a Synthetic Orthodontic Elastomer

Abstract: The study focused on changes in elasticity that accompany water storage of a synthetic orthodontic elastomer. We plotted loading and unloading curves to permit the direct measurement of instantaneous elastic recovery (IER) and permanent set (PS) and the calculation of delayed recovery (DR). We obtained baseline data by testing dry as received material. Comparable tests were performed on material that had been stored in water at 37 degrees C for one, seven, 14, 42, and 70 days. Gas chromatography-mass spectrometry was used for analysis of organic substances leached from the elastomer by water. A two-way ANOVA revealed that extension distance and water storage duration affected load requirement, IER, PS, and DR. The presence of leachable organic substances in 14-, 42-, and 70-day storage water was evidence of time-dependent matrix decomposition. Findings from tests of elastic performance and analysis of specimen storage water indicate that exposure of the elastomer to water leads first to weakening of noncovalent forces and subsequently to degradation.

Comparative distribution of carbonic anhydrase isozymes III and II in rodent tissues.

Abstract: Carbonic anhydrase (CA) III was demonstrated immunocytochemically in epithelium in some regions of salivary gland ducts, colon, bronchi, and male genital tract and in adipocytes, in addition to skeletal muscle and liver where the isozyme was previously localized. Basal cells beneath the submandibular gland's excretory ducts in guinea pig stained for CA III. Carbonic anhydrase III occurred alone in some and with CA II in other sites but was often absent from CA-II-containing types of cells. This was exemplified by CA III's abundance in CA-II-positive proximal colon and its sparsity in the CA-II-rich distal colon of the mouse. Striated ducts in guinea pig, but not mouse salivary glands, stained darker for CA and appeared accordingly to function more actively in ion transport compared with excretory ducts. Carbonic anhydrase content varied among genera in liver and pancreas and between mouse species and strains in salivary glands and kidney. Newly observed murine sites of CA II activity included Auerbach's plexus and a population of leukocytes infiltrating the lamina propria in small intestine, and several types of cells in the male genital tract. In immunoblot tests, antisera to CA III showed no cross reactivity with antisera to CA II, but those to CA II disclosed weak cross reactivity with CA III.

Methicillin-Resistant Staphylococcus aureus Outbreak at a Veterans' Affairs Medical Center: Importance of Carriage of the Organism by Hospital Personnel

Abstract: The reported prevalence of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) by hospital personnel averages 2.5%. From August 1985 to September 1987, 155 patients at our Veterans' Affairs Medical Center (VAMC) were colonized or infected with MRSA. In December 1986, only two (2.1%) of 94 healthcare workers were identified as nasal carriers. Prompted by a sharp increase in the number of patients with MRSA in early 1987, contact tracing identified 450 employees, of whom 36 (8%) were nasal carriers. Thirty-five percent of surgical residents (7 of 20) were nasal carriers. Prior to being identified as a nasal carrier, one surgical resident was associated with the inter-hospital spread of the VAMC MRSA strain to the burn unit of the affiliated university hospital. Three family members of two employee carriers were also found to harbor the epidemic strain. All 36 carriers were decolonized with various antimicrobial combinations. Vigorous infection control measures were effective in controlling the epidemic. The frequency of MRSA carriage by hospital personnel at our medical center during the epidemic proved higher than previously appreciated. Thus, healthcare workers may comprise a sizable MRSA reservoir. During an MRSA epidemic, infection control should attempt to identify and decolonize this hospital reservoir, as these individuals can disseminate MRSA both within the hospital as well as into the community.