Role of vasoconstrictor mechanisms in the control of left ventricular performance of the normal and damaged heart.

The effect on the left ventricle of changes in the state of the arterial vasculature is best identified by utilizing calculations of pulsatile rather than steady flow phenomena. Impedance is the most satisfactory term to describe this effect. The normal ventricle compensates for changes in impedance largely by changes in preload, but the damaged heart loses this compensatory ability and its stroke volume becomes inversely related to outflow resistance. Patients with heart failure behave in a similar fashion and pharmacologic vasodilation may induce marked improvement in left ventricular pump function. Inappropriate vasoconstriction in heart failure may result from stimulation of the sympathetic or renin-angiotensin system. Early experience with converting enzyme inhibitors suggests that blockade of the formation of angiotensin II may be a useful means of treating some patients with heart failure.     

Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation

To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring. Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings. The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient. These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient.     

Induction of replicative DNA synthesis in quiescent human fibroblasts by DNA damaging agents.

A marked induction of DNA replication was observed in confluent human diploid fibroblast cultures treated with low relatively nontoxic doses of UV radiation, N-methyl-N-nitrosourea (MNU), and N-acetoxy-2-acetylaminofluorene (AAAF). Isopycnic CsCl density gradient analysis of newly synthesized DNA labeled with BrdUrd indicated that most of the synthesis was semiconservative. The rate of semiconservative DNA synthesis was maximal 24 hr after damage. This induction of DNA replication was greatest at approximately equal to 3 J/m2 UV, 0.5 mM MNU, or 1.0 microM AAAF; was inhibited by hydroxyurea and aphidicolin; and also occurred in repair-deficient xeroderma pigmentosum fibroblasts. Autoradiographic examination of both confluent cultures and serum-arrested cultures showed a large increase in the fraction of densely labeled (S phase) cells after UV treatment. These densely labeled cells retain the capacity for cell division and subsequent proliferation. We conclude that low doses of at least three different DNA damaging agents are capable of recruiting quiescent cells into a state of DNA replication similar to that observed in the normal cell cycle.     

A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twice-weekly, directly observed, and cost-effective regimen

STUDY OBJECTIVE: To evaluate the efficacy and toxicity of a 62-dose, four-drug, 6-month, and directly observed regimen for treatment of pulmonary and extrapulmonary tuberculosis. DESIGN: An open, nonblinded clinical trial, with intended follow-up of patients for 36 months after the completion of therapy. SETTING: A metropolitan tuberculosis clinic in a public health department. PATIENTS: From March 1981 through April 1989, we enrolled 160 patients with suspected or known tuberculosis; 35 of these patients were excluded from the analysis. INTERVENTIONS: Isoniazid, rifampin, pyrazinamide, and streptomycin were administered daily for 2 weeks; these drugs were then given in higher doses twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 18 weeks. A total of 62 doses were administered, and all therapy was directly observed by a nurse or an outreach worker. MEASUREMENTS AND MAIN RESULTS: Of the 125 evaluable patients, 101 (81%) had pulmonary tuberculosis, 7 (6%) had both pulmonary and extrapulmonary involvement, and 17 (13%) had extrapulmonary disease only. Seventy-one (57%) patients had a history of recent alcoholism. There were two relapses (1.6% +/- 2.2%), occurring 6 and 56 months after the completion of therapy. The time at which sputum samples became culture negative in pulmonary patients ranged from 1 to 19 weeks (median, 4.6 weeks); 40% +/- 9.6% of patients were culture-negative after 4 weeks of therapy, 75% +/- 8.5% after 8 weeks, 94% +/- 4.7% after 12 weeks, 97% +/- 3.3% after 16 weeks, and 100% after 20 weeks. Adverse drug reactions included hyperuricemia (greater than 178 mumol/L [3 mg/dL] above normal) secondary to pyrazinamide in 80 patients (64%), twofold or greater elevations of aspartate aminotransferase in 21 patients (17%), 1.5-fold or greater elevations of alkaline phosphatase in 33 patients (27%), cutaneous abnormalities in 8 patients (6%), nausea in five patients (4%), and dizziness in 1 patient (1%). CONCLUSIONS: This 62-dose, largely twice-weekly tuberculosis treatment regimen is efficacious and relatively nontoxic and is especially useful for patients in whom directly observed therapy is indicated.     

Media and political framing of crystal methamphetamine use in Australia

Abstract

Media and politicians both influence public opinion and policy responses to illicit drug issues. This study examines the contribution each may have made in Australia in 2015 to the problem and politics streams of the policy process, as outlined in Kingdon’s ‘multiple streams’ heuristic, when a National Ice Taskforce responded to increased public, political and media concern about methamphetamine use. A retrospective content analysis compared the frequency and content of articles about methamphetamine in print media (N?=?639) and federal parliament speeches (N?=?158) in 2015. Peaks in the number of media articles and debates in parliament followed the establishment and interim findings of the Ice Taskforce. The findings showed that politicians more frequently framed methamphetamine use as a crisis or epidemic than the media. Both frequently portrayed cost to society as the consequence of methamphetamine use and often cited law enforcement sources. The media most frequently positioned methamphetamine users as criminal or deviant compared to politicians who did not position the user or positioned them as an addict or victim. This analysis highlights the convergence of the problem and politics streams and suggests they are not independent as first posited by Kingdon.     

Comparison of selective left ventriculograms with levophase ("forward") ventriculograms in patients with coronary artery disease.

In order to compare levophase ("forward") ventriculograms to standard (selective) LV cineangiography, 10 patients with coronary artery disease were studied by (1) selective injection of contrast medium into the LV cavity followed by (2) injection into the right ventricle and filming the levophase. Biplane cineangiograms were used to calculate the end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), and ejection fraction (EF). Values for the two respective techniques were then compared. Not only were correlation coefficients for the two methods low, but there was also a statistically significant difference between the two SVI (66 +/- 26 ml. for selective and 53 +/- 25 ml. for levophase injection; p less than 0.02) and the two EF (67 +/- 7 per cent for selective and 52 +/- 12 per cent for levophase injection; p less than 0.01). Levophase cineangiograms therefore significantly underestimate the LV ejection fraction when compared to standard (selective) LV cineangiography. These differences must be considered when evaluating greatly divergent interinstitutional survival rates for patients with low EF who undergo coronary artery bypass surgery, and when selecting candidates for bypass surgery on the basis of the angiographic data.     

Unreliability of exercise-induced R wave changes as indexes of coronary artery disease

To investigate the diagnostic value of exercise-related QRS amplitude changes, the responses of 40 young normal subjects and 28 patients with chest pain and no significant coronary arterial obstruction were compared with those of 73 patients with coronary arterial narrowing of various degrees of severity. All underwent submaximal, multiple lead multistaged treadmill exercise testing. The combined normal group showed an average decrease in R wave amplitude between rest and exercise of 1.1 ± 2.8 mm (mean ± standard deviation) in lead V₅; those with coronary artery disease had an increase of 0.6 ± 3.4 mm (P = 0.001). Similar but less pronounced differences were observed in lead II (a decrease of 1.9 ± 2.3 mm in normal subjects versus a decrease of 0.5 ± 3.1 mm in those with coronary disease, P = 0.01). When derived R wave criteria were used, the test sensitivity averaged 52 percent and the specificity 63 percent; these values were inferior to the sensitivity of 88 percent and specificity of 72 percent of S-T segment criteria in the same group of patients. No significant relation was found between the extent of coronary artery disease and R wave changes, and an analysis of multiple variables suggested possible correlations with factors not directly related to ischemia. It is concluded that exercise-induced QRS amplitude changes are unreliable predictors of the presence, absence or severity of coronary artery disease.     

Specialty training and specialization among physicians who treat HIV/AIDS in the United States

OBJECTIVE: To assess the association of specialty training and experience in the care of HIV disease with HIV-specific knowledge, referral patterns, and HIV-related education activities. DESIGN: Cross-sectional survey. SETTING: The United States. PARTICIPANTS: Physicians caring for patients in the HIV Costs and Service Utilization Study, a study of a probability sample of HIV-infected individuals in the United States. MEASUREMENTS AND MAIN RESULTS: Measures included physicians' reports of specialty training and HIV caseload, scores on an HIV-specific knowledge test, referral patterns, and attendance rates at HIV-related educational activities. Approximately 72% (379) of the eligible physicians completed a survey. Of these, 152 (40%) had infectious disease (ID) training, and 213 (56%) were generalists; 4% of ID-trained physicians and 37% of generalist physicians did not consider themselves HIV experts. The median current caseloads were 150 and 200 patients for ID experts and generalist experts, respectively. In contrast, the median caseload for non-expert generalists was 5. Mean scores on the knowledge scale were similar for ID and generalist experts (9.0 items correct out of 11 vs 8.5; P=not significant), but lower for generalist non-experts (6.5 items correct; P <.01). Experts had attended more local and national HIV meetings than non-experts (9.3 vs 2.7; P <.01, and 2.3 vs.40; P <.01, respectively) in the past year. Fewer ID experts ever referred than generalist experts (13.0% vs 27.3%; P=.01). In multivariable models that included specialty training and caseload, physicians with caseloads of 20 to 49 and >50 were more likely to have a high knowledge score (defined as 80% or more correct, odds ratio [OR], 2.8; P=.04 and OR, 5.7; P <.001, respectively), and the effect of specialty was attenuated (OR, 2.7; P=.02 decreased from OR, 7.8; P <.001 in a model without caseload). In the models predicting referral practices, both experience (OR,.25; P <.01 and OR,.17; P <.01 for caseloads of 20 to 49 and >50, respectively) and specialty (OR,.19; P <.01 and OR,.09; P <.01 for generalist and ID experts, respectively) were significant. CONCLUSIONS: In a national sample of physicians, HIV-specific knowledge was more strongly associated with HIV caseload than with specialty training. In addition, although referral practices were related to both experience and specialty, generalist experts and ID physicians reported similar behaviors. This suggests that generalist physicians, through clinical experience and self-education, can develop specialized knowledge in HIV care.