Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

Start Talking About Risks: Development of a Motivational Interviewing-Based Safer Sex Program for People Living with HIV

The epidemiology of HIV infection in the US in general, and in the southeast, in particular, has shifted dramatically over the past two decades, increasingly affecting women and minorities. The site for our intervention was an infectious diseases clinic based at a university hospital serving over 1,300 HIV-infected patients in North Carolina. Our patient population is diverse and reflects the trends seen more broadly in the epidemic in the southeast and in North Carolina. Practicing safer sex is a complex behavior with multiple determinants that vary by individual and social context. A comprehensive intervention that is client-centered and can be tailored to each individual’s circumstances is more likely to be effective at reducing risky behaviors among clients such as ours than are more confrontational or standardized prevention messages. One potential approach to improving safer sex practices among people living with HIV/AIDS (PLWHA) is Motivational Interviewing (MI), a non-judgmental, client-centered but directive counseling style. Below, we describe: (1) the development of the Start Talking About Risks (STAR) MI-based safer sex counseling program for PLWHA at our clinic site; (2) the intervention itself; and (3) lessons learned from implementing the intervention.     

Situs inversus with hypertrophic cardiomyopathy in identical twins

We describe identical twin sisters born to nonconsanguineous, healthy parents. Both twins had situs viscerum inversus and developed hypertrophic cardiomyopathy in adulthood.     

Hemothorax in a patient with asthma

Treatment of chronic illnesses such as asthma can often become routine. This is a case report that emphasizes the importance of a thorough history and physical examination for each exacerbation of asthma. An 11-year-old girl with a history of asthma presented to the emergency room with wheezing and dyspnea that was assumed to be an exacerbation of her chronic illness. After careful history taking and physical examination, a chest radiograph was recommended. The x-ray revealed a hemothorax and a new diagnosis was made, thoracic Ewing's sarcoma.     

Nuclear type-ii [h-3] estradiol binding-sites in mcf-7 human breast-cancer cells - binding interactions with 2,6-bis-([3,4-dihydroxyphenyl]-methylene)cyclohexanone esters and inhibition of cell-proliferation

Previous studies from this laboratory demonstrated that 2,6-bis-([3,4-dihydroxyphenyl]methylene)cyclohexanone (BDHPC) and related compounds mimic methyl p-hydroxyphenyllactate (MeHPLA) as endogenous ligands for nuclear type II [H-3]estradiol binding sites. Occupancy of type II sites by these agents results in the inhibition of malignant cell proliferation in vitro and mammary tumor growth in vivo. The present studies were designed to assess the effects of BDHPC esterification on type II site binding interactions in uterine nuclei and in cultured MCF-7 human breast cancer cells in vitro. The results of these experiments demonstrate that in rat uterine nuclear fractions BDHPC acetate (Kd approximately 100 nM) interacts with type II sites with a 100-fold lower affinity than BDHPC (Kd approximately 0.9 nM) and BDHPC benzoate failed to inhibit [H-3]estradiol binding under these experimental conditions. Conversely, BDHPC and BDHPC acetate displayed very similar binding affinities for type II sites in cultured MCF-7 human breast cancer cells and there was a direct correlation between nuclear type II site occupancy and the inhibition of cellular proliferation by these two compounds. BDHPC benzoate failed to interact with type II sites or inhibit MCF-7 cell proliferation. Taken together, these results suggested that BDHPC acetate, but not BDHPC benzoate, was being hydrolyzed by esterases in MCF-7 cells, releasing the free parent compound. This conclusion was supported by the observations that incubation of BDHPC acetate in mammary tumor cytosol preparations resulted in essentially quantitative hydrolysis to BDHPC as determined by thin layer chromatography (TLC) and by high performance liquid chromatography (HPLC) analysis of tumor cytosol extracts. Conversely, BDHPC benzoate was not hydrolyzed by tumor esterases which is consistent with the inability of this compound to bind to type II sites or inhibit MCF-7 human breast cancer cell proliferation. These experiments confirm and extend the hypothesis that esterase hydrolysis of MeHPLA related compounds represents an important biological step involved in the control of the biological activity of type II site agonists which appear to regulate malignant cell proliferation through this binding interaction.     

An open study of sertraline in patients with major depression who failed to respond to moclobemide

OBJECTIVES: The aim of this study is to evaluate the efficacy and tolerability of sertraline in patients with major depression who have failed to respond to an adequate trial of moclobemide. METHOD: Sixty-three patients with major depression who had discontinued moclobemide within the last 6 weeks due to lack of efficacy were recruited from multiple psychiatric services in Victoria and Queensland. After a wash-out period, patients were treated with sertraline 50 mg once daily for 4 weeks. If there was an insufficient response, the dose was titrated upwards to a maximum of 200 mg/day, with 2 weeks at each dosage level. By the end of the study, patients had received a fixed dose of sertraline for 8 weeks. The main outcome measures were the 17-item Hamilton Rating Scale for Depression (HAMD) and Clinical Global Impression (CGI) scales. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). RESULTS: Of the 62 intention-to-treat patients enrolled, 48 (77%) responded to sertraline (i.e. experienced > or =50% reduction in HAMD total score from baseline and had a final HAMD score of < or =17). Fifty-four (87%) patients were at least 'minimally improved' on the CGI scale. There were also significant improvements in mean total MADRS and BDI scores. Sertraline was well tolerated. Adverse events were reported by 84% of patients, but only 5% withdrew due to adverse events. CONCLUSIONS: This study shows that patients with major depression who have failed to respond to moclobemide can generally be treated successfully with sertraline.     

Single shot intraoperative excretory urography for the immediate evaluation of renal trauma

PURPOSE: We reviewed the quality and usefulness of single shot intraoperative excretory urography (IVP) for evaluating suspected upper urinary tract trauma at our trauma center. MATERIALS AND METHODS: Between 1990 and 1997 single shot intraoperative IVP for staging renal injuries was performed in 50 patients in whom clinical instability and/or major associated injuries mandated an intraoperative study. Contrast material (2 ml/kg) was injected intravenously and images were obtained after 10 minutes. The quality and usefulness of each study were scored by a single attending urologist on a scale of 1-worst to 5-best. RESULTS: Intraoperative study quality was generally good (average score 3.84). The information obtained was generally considered useful for determining urological treatment (average score 3.96). In 16 patients (32%) intraoperative IVP findings safely obviated renal exploration. No contrast medium reactions were noted and no complications developed that were attributable to intraoperative IVP. CONCLUSIONS: Intraoperative single shot, high dose IVP is safe, efficient and of high quality in the majority of cases when performed as recommended. This study often provides important information that facilitates rapid and accurate decision-making. Intraoperative IVP is a useful tool for guiding the exploration of penetrating renal injuries and confirming blunt renal injuries that may be safely observed.     

Autonomic blockade and the Valsalva maneuver in patients on maintenance hemodialysis: a hemodynamic study

Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at rest. Cardiac output, mean intraarterial pressure, and the calculated total peripheral resistance index were recorded while the patients were at rest and during acute "total" autonomic blockade. On the sodium diet of 10 mmoles/day, normotensive and hypertensive patients had similarly low total blood volumes, low-normal ECF volumes, and similar levels of plasma renin and aldosterone. The resting cardiac output was increased in both groups, but the total peripheral resistance was increased only in the patients with hypertension, in whom peripheral resistance was inappropriately high for the degree of anemia. Six hypertensive patients were studied on both diets. The resting mean arterial pressure was greater on the sodium diet of 100 mmoles/day than on the 10 mmoles/day diet, accompanied by increased in plasma volume, extracellular fluid volume, and cardiac output, but no change in peripheral resistance. During autonomic blockade on either diet, there was a marked fall in blood pressure in the patients with hypertension. This was mainly due to a fall in peripheral resistance which reached levels similar to those seen in the normotensive patients whose resistance was unaltered by blockade. Autonomic factors appear to contribute to the elevated peripheral resistance of hypertensive dialysis patients. In these patients, the effect of a high sodium diet, at least over the time-scale studied here, is to increase blood pressure and cardiac output, without the change in peripheral resistance expected from autoregulation.