In-hospital needlesticks and other significant blood exposures to blood from patients with acquired immunodeficiency syndrome and lymphadenopathy syndrome

There have been no documented cases of acquired immunodeficiency syndrome (AIDS) in personnel after a prospectively recognized in-hospital blood exposure. To assess the frequency of such exposure the membership of the Association for Practitioners in Infection Control was surveyed in early June 1983. Thirty-three percent of the membership responded, accounting for 42% of U.S. hospitals with more than 250 beds. Respondents reported needlestick or other significant blood exposures to blood from patients with AIDS occurring in 157 instances and to blood from patients with lymphadenopathy syndrome in 43 instances. Nineteen and twenty of the exposures, respectively, occurred before July 1982. There are two bases for believing that AIDS will not pose a substantial risk to hospital workers: the lack of demonstrated in-hospital AIDS transmission to date and the recognition that other viruses besides the hepatitis B virus--viruses that seem to have less potential for in-hospital transmission--are equally plausible models of AIDS transmission.     

Hypocellular acute leukemia

We examined the clinical features and therapeutic response of a group of patients with acute leukemia and hypocellular bone marrow. Therapists have generally avoided, delayed or modified therapy because of hypocellularity. We demonstrated not only that aggressive therapy is possible, but also that the remission rate is high (complete remission = 73 percent) and survival prolonged (x? > 40 months).     

Decline in blood flow in stenotic coronary arteries during increased myocardial energetic demand in response to pacing-induced tachycardia

It is generally belleved that blood flow (CBF) in a severely stenotic coronary artery does not change, or only increases to a maximum limited by the obstruction, in response to increased myocardial oxygen demand in coronary artery disease (CAD). The effects of ventricular pacing on pressure and flow in critically stenotic coronary arteries were studied in six open-chest dogs. A critical stenosis was produced in the circumflex coronary artery with a soft wire snare. CBF in the circumflex (Cx) and left anterior descending (LAD) coronary arteries were measured with electromagnetic flow probes. Aortic pressure, coronary pressure distal to the stenosis, and heart rate (HR) were also measured. In Cx arteries with no stenosis, increasing HR from 59 ± 6 to 153 ± 5 bpm increased CBF from 26 ± 2 to 44 ± 3 ml/min (p < 0.01). When the snare was tightened so that a critical stenosis was produced, increasing HR from 65 ± 3 to 157 ± 4 bpm caused a fall in CBF in the stenotic Cx artery from 23 ± 2 to 15 ± 2 ml/min (p < 0.001). This fall in CBF was associated with a decrease in distal Cx artery pressure (66 ± 3 to 31 ± 2 mm Hg;p < 0.001) and a rise in large artery resistance (2.1 ± 0.4 to 7.7 ± 2.3 units;p < 0.05). In these experiments, CBF in the normal LAD increased from 29 ± 3 to 55 ± 7 ml/min (p < 0.001). Mean aortic pressure did not change significantly (110 ± 3 to 105 ± 4 mm Hg). The fall in Cx flow and distal Cx pressure tended to persist after cessation of pacing. These studies suggest that an increase in myocardial oxygen demand may result in a paradoxical fall in flow in a stenotic coronary artery, and that this reduction in flow may persist after the metabolic stress is relieved.     

Pressure pulse contour analysis in determining the effect of vasodilator drugs on vascular hemodynamic impedance characteristics in dogs

The effects of three vasodilators on the shape of the arterial pressure contour in the dog were investigated. A modified Windkessel model of the arterial vasculature was used as a guide in interpreting the observed contour changes. The pressure curve during diastole has been viewed as the transient response of the arterial system and can be fit accurately to the equation The parameters in this equation and peripheral resistance were used to define the components of the third order Windkessel model consisting of proximal (C₁) and distal (C₂) compliances, an inertance term (L), and peripheral resistance (R). This model describes the gross mechanical behavior seen in the arterial system during diastole. The arterial pressure pulse, mean pressure, and cardiac output responses to intravenous administration of sodium nitroprusside (NP), nitroglycerin (NTG), and hydralazine (H) were studied using computerized parameter estimating techniques to determine the a_i parameters in the pressure equation and their relationship to the Windkessel components. All three drugs caused C₁ to decrease, but not significantly. NTG increased inertance from 0.076 to 0.134 mm. Hg/ml./sec.², with a p value < 0.05. NP increased C₂ from 0.027 to 0.046 ml./mm. Hg. (p < 0.01); NTG also increased C₂, from 0.030 to 0.060 ml./mm. Hg (p < 0.05). Hydralazine had no significant effect on C₂, but it did reduce R from 3.10 to 2.16 mm. Hg/ml./sec. (p < 0.01). Neither NP nor NTG showed a significant decrease in R. Thus, the three vasodilators apparently have different vascular effects, as demonstrated by the pulse contour analysis. Such an analysis may be a useful way to evaluate vasodilator therapy.     

Q-T interval in sinus arrhythmia

The Bazett equation is modified for calculating the “corrected Q-T” in children with sinus arrhythmia.     

Stimulation of malic enzyme formation in hepatocyte culture by metabolites: Evidence favoring a nonglycolytic metabolite as the proximate induction signal

Recent studies have shown that the addition of increasing concentrations of glucose to the medium of primary adult rat hepatocyte cultures results in the progressive induction of malic enzyme. We have undertaken experiments to determine (1) whether metabolism of glucose was an essential prerequisite for such induction, and (2) whether a specific glycolytic intermediate could be shown to constitute the proximate carbohydrate signal triggering such induction. In line with these objectives we investigated the ability of various sugars and glycolytic metabolites to induce malic enzyme in this system and assessed the influence of insulin, glucagon, and thyroid hormone (triiodothyronine, T₃) on this process. Our results show that only those sugars capable of entering the cell and being metabolized induce malic enzyme (glucose, fructose, and galactose). The nonmetabolizable sugars 3-O-methylglucose and 2-deoxyglucose are ineffective. Incubation with 20 mmol/L lactate, pyruvate, dihydroxyacetone, or glycerol resulted in malic enzyme induction, whereas incubation with acetate, citrate, and α-ketoisocaproate was without effect. The induction by all sugars and metabolites required presence of insulin. As previously reported for glucose, addition of T₃, under all metabolic conditions, resulted in a constant 3.6-fold increase in the rate of malic enzyme induction and further supports the proposal that T₃ acts to multiply the effect of a common carbohydrate-generated signal. Glucagon administration led to a dose-dependent inhibition of the carbohydrate effect with a half-maximal effect and maximal effect at 2 and 100 nmol/L, respectively. None of the glycolytic metabolites tested could reverse the glucagon inhibition completely. Our results indicate that metabolism of glucose is essential for induction of malic enzyme and are most consistent with the view that the signal arises from the metabolism of pyruvate at a step before the formation of cytsolic acetyl-CoA. Since these processes are mitochondrial in location, it appears likely that this organelle is the site of origin of the inducing signal. Of some interest in this connection was the finding that dichloroacetate led to a major induction of malic enzyme, even in the absence of insulin and in the presence of glucagon. The ability of dichloroacetate to bypass the glucagon block thus further supports a nonglycolytic origin of the inducing signal.     

Effect of clofibrate and colestipol singly and in combination on plasma lipids and lipoproteins in type III hyperlipoproteinemia

The effects of colestipol, clofibrate, and a combination of these two drugs on plasma lipid and lipoprotein values were evaluated in seven subjects with type III hyperlipoproteinemia. When compared to baseline, colestipol administration resulted in a significant decrease in LDL-cholesterol (146 v 99, P less than 0.01) and a significant increase in VLDL-triglycerides (260 v 399, P less than 0.05). The increases in total triglycerides (346 v 462, P = 0.09) and VLDL-C (117 v 155, P = 0.17) noted with colestipol were not statistically significant. Clofibrate administration increased HDL-C (37 v 46, P less than 0.05), and lowered VLDL-C (117 v 56, P less than 0.05), VLDL-triglycerides (260 v 144, P less than 0.05) and total triglycerides (346 v 218, P less than 0.01). The combined regimen was more effective than clofibrate in lowering total and LDL-cholesterol, and no other significant differences were noted.     

Coronary arteriographic findings in patients with axis shifts or S-T-segment elevations on exercise-stress testing

The exercise ECG's and coronary arteriograms of 158 patients were examined to evaluate the relationship of exercise-induced axis shifts and S-T-segment elevations to coronary artery disease. Eighteen of the 158 patients had exercise-induced S-T-segment elevations. Seventeen of these 18 patients had severe obstruction of the major coronary artery most compatible with the zone of ischemic localization. This obstruction was greater than 85 per cent in 16 patients and greater than 50 per cent in a seventeenth patient. The remaining patient had a normal coronary arteriogram and the most minimal exercise-induced S-T-segment elevations. Nine of the 158 patients had exercise-induced right axis shifts. Only 4 of these 9 patients had greater than 50 per cent obstruction of a major coronary artery, as compared to 103 of 154 patients in the total group studied. Also, there was no trend toward predominant involvement of any particular coronary artery in these 4 patients. Hence, it appears that this finding is not predictably associated with severe localized coronary artery disease. Only 4 of the 158 patients had exercise-induced left axis shifts. Three of these four patients had complete obstruction of the left anterior descending artery. But the group size was small, and the fourth patient had a normal coronary arteriogram. Hence, it is only possible to suggest that this finding may be associated with severe disease of the left anterior descending artery. The results of coronary artery surgery are discussed in a patient who had both a left axis shift and precordial S-T-segment elevations on his preoperative exercise ECG.     

Inhibition of malic enzyme induction by triiodothyronine in the diabetic rat: Reversal by fructose feeding

In order to determine whether an increase in insulin is a prerequisite for induction of malic enzyme (ME) by triiodothyronine (T₃), we examined the ability of various diets to affect the T₃ induction of ME in diabetic rats. Forty-eight hours after streptozotocin, rats were placed on either a regular diet, a 60% glucose diet, or a 60% fructose diet. The next day selected groups received 200 μg T₃/100 g body weight. Twenty-four hours later serum was collected and the liver 100,000 × g supernatant fraction was assayed for ME. Compared to intact controls, the level of ME in the basal state as well as in the T₃ stimulated state was significantly less in diabetic rats (in U/mg, basal: intact, 19.3; diabetic, 7.1; T₃-treated:intact, 56.6; diabetic, 15.6). Fructose feeding in the diabetic rats led to no significant increment in ME (1.1 U/mg) whereas the intact rat fed fructose showed a significant increment in ME (39.4 U/mg). The combined administration of fructose and T₃ in the diabetic rat however, resulted in a substantial increment of ME (30 U/mg), which was significantly greater than the increment induced by T₃ and glucose (2 U/mg). Moreover, the increment in ME induced by T₃ and fructose in diabetic animals was not significantly different from that achieved in intact animals (54.9 U/mg). All groups of diabetic rats showed a decrease in insulin from the start of the dietary manipulations to the end of the experiment (28.7 μU/ml fasting to 10.9 μU/ml when killed in the fed state). Thus ME induction by T₃ can occur in the absence of an increase in insulin secretion. Fructose feeding can supply, at least in part, the necessary factors that permit T₃ to induce ME in diabetic rats.     

The idiopathic hyperkinetic heart syndrome: clinical course and long-term prognosis

Nineteen of the originally reported 24 patients having the idiopathic hyperkinetic heart syndrome were followed for periods of 11 to 25 years. One patient died of complicating severe mitral stenosis. Of the remaining 18 patients, nine had complete physical examinations and ECG records. Only one of these patients was symptomatic at the time of reexamination. Murmurs originally present in eight of nine patients were present in only five of nine at reexamination; hyperkinetic circulation and heart, originally present in eight, were found in only two at follow-up; and systolic hypertension, present in seven at beginning of the study, was only present in four at follow-up. ECG abnormalities (usually left ventricular hypertrophy) regressed in the majority. Persistent elevation of cardiac index and systolic ejection rate were found at repeat catheterization in the single symptomatic patient who had congestive cardiomyopathy. Uncomplicated idiopathic hyperkinetic heart syndrome appears to have an excellent long-term prognosis.     

The synthesis of insulin and proinsulin in a cell-free system derived from the streptozotocin-nicotinamide--induced rat islet adenoma

Preliminary studies were conducted to develop a cell-free system for insulin biosynthesis using the streptozotocin-nicotinamide--induced rat islet adenoma. Radiolabeled proteins, migrating on steric exclusion chromatography and SDS-gel electrophoresis in the region of insulin and proinsulin, were synthesized in a system prepared from the tumor 800 X g supernatant fraction, rat liver cytosol, and appropriate energy substrates. The proteins were not synthesized by a rat liver cell-free system, and synthesis could be substantially inhibited by the addition of cycloheximide. In addition, it could be shown that the islet proteins were not the products of residual intact cells within the system, nor were they an artifact due to nonspecific binding of [3H]-L-leucine to pre-existing insulin and proinsulin. The radiolabeled material eluting with insulin on steric exclusion chromatography was identified as [3H]-insulin by immunoaffinity column chromatography.