The effects of stress on left ventricular ejection fraction

The left ventricular ejection fraction (EF) was studied in 17 healthy volunteers with a new ambulatory left ventricular function monitor. Heart rate, EF, and blood pressure measurements were made during rest, a psychiatric stress interview, cold exposure, exercise, and eating. An increase in EF was seen during emotional stress (from 0.45±0.09 to 0.51±0.13, P<0.001). This increase was comparable to that observed during exercise (0.52±0.14) and eating (0.52±0.10, P<0.001). In contrast, cold exposure caused a decrease in EF (0.43±0.13, P<0.05). These observations demonstrate the powerful hemodynamic consequences of common behaviors as well as the utility and feasability of studying such behavioral factors in ambulatory subjects.Supported in part from grants HL24623 and HL36005 from the National Institutes of Health and by fellowships from the Canadian Heart Foundation (Dr. Kiess) and the Medical Research Council of Canada (Dr. Liu)     

Tumour necrosis factor in man: clinical and biological observations

Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.     

An Epidemiologic Approach to Assessing Primary Care Needs in Rural Illinois

One persistent problem that faces state and federal health policy-makers is determining the level of primary care needs of the citizens they serve. To refine the decision making process in Illinois, a model was developed to compare the 84 rural counties of Illinois and their potential need for additional primary care interventions. Using expert panel methods, a group of public health professionals selected a set of 31 health status indicators that were available at the county level throughout the state. Next, the panel developed a weighting system for those indicators. These weighted values were then applied to the demographic and epidemiologic data from each of the counties to rank the counties on the basis of need. Indicators having the highest correlation with the weighted sum were the percent of the population enrolled in Medicaid, lung cancer mortality rate, general population mortality rate, proportion of population at poverty level, and percent of births to teens. Data also showed that the rural counties with the greatest needs clustered in five geographic regions. The identification of these five geographic clusters may facilitate collaborative efforts in meeting the primary care needs of these populations.     

Changing trends in feeding policies for ventilated preterm infants

In 1987 and 1994 all UK regional neonatal intensive care units were questioned about their feeding policies for the ventilated preterm infant. Between 1987 and 1994 there was an increase in the use of milk feeds (59 versus 71%), fortified breast milk (5 versus 72%) and low birthweight formula (41 versus 69%) whilst use of donor breast milk declined (56 versus 22%). Units that gave enteral feeds used significantly less parenteral nutrition ( p < 0.05). Overall there was a tendency towards greater uniformity in feeding policies.     

The effect of potassium ion depletion on postinfarction canine cardiac arrhythmias

The effect of potassium ion (K+) depletion on postmyocardial infarction ventricular arrhythmias was investigated in 32 dogs: 12 control animals, 10 animals that ate a diet extremely low in K+ for 15 days, and 10 others that, in addition to dietary K+ deprivation, received 50 mg of hydrochlorothiazide four times. The experimental myocardial infarction was created by proximal left anterior descending coronary artery ligation. In a subgroup of 24 animals selected for relatively uniform size of myocardial infarction (14% to 22% of left ventricular mass), eight animals with mean cumulative K+ balance of -4.01 +/- 2.19 meq/kg developed spontaneous ventricular fibrillation within 4 to 17 min of coronary ligation, whereas 16 animals with a mean cumulative K+ balance of -0.11 +/- 1.82 meq/kg didn't. By univariate analysis cumulative K+ deficit (p = .001) and plasma K+ concentration (p = .039) correlated significantly with spontaneous ventricular fibrillation. Multivariate analysis of the entire population of 32 animals identified cumulative K+ deficit and size of myocardial infarction as the only independent predictors of ventricular fibrillation. Cumulative K+ deficit was also an independent predictor of ventricular fibrillation induced by programmed cardiac stimulation in the conscious state 1 day after myocardial infarction.     

Reduction of intracellular pH as a possible mechanism for killing cells in acidic regions of solid tumors: effects of carbonylcyanide-3-chlorophenylhydrazone

The environment of cells within solid tumors is known to be acidic relative to that in normal tissue, and the viability of tumor cells may depend on mechanisms which maintain intracellular pH (pHi) above the extracellular pH (pHe). We have assessed therefore the toxicity in vitro of the proton ionophore carbonylcyanide-3-chlorophenylhydrazone (CCCP), since this agent has been reported to be capable of transporting H+ equivalent through artificial lipid bilayers and mitochondrial membranes. CCCP was toxic to the human bladder carcinoma cell line MGHU1 and to the murine mammary sarcoma cell line EMT-6 only at pH, less than 6.5. CCCP transported H+ equivalents through cell membranes at physiological (7.35) and low pHc (6.20). Cell lines were found to have steady-state pHi values approximately 0.1 to 0.2 pH units above pHc at pHc less than 6.50. Addition of CCCP led to a decrease in steady-state pHi values as compared to untreated cells at pHc less than 6.50, whereas there was no apparent effect of CCCP on steady-state pHi values at pHc greater than 6.50. The CCCP-induced reduction in steady-state pHi combined with the uncoupling of oxidative phosphorylation by CCCP appeared to be the major mechanisms leading to cell death at pHc less than 6.50. The toxicity of CCCP under acidic conditions was enhanced by amiloride and 4,4'-diisothiocyanostilbene-2,2-disulfonic acid, agents which are known to inhibit membrane-based ion exchange mechanisms which regulate pHi under acidic conditions. When both agents were combined with CCCP, cell killing was observed at pHc less than 7.30. Our results suggest that mechanisms which regulate pHi under acidic conditions which occur in solid tumors may represent targets for new forms of tumor-specific therapy.     

Incidence and anatomic distribution of cutaneous melanoma among United States Hispanics

Using the data base for melanoma incidence compiled by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we compared the incidence and anatomic distribution of primary cutaneous melanomas in Hispanic and non-Hispanic Caucasian populations and in blacks between 1973 and 1981. Cases were divided into United States whites, New Mexico (NM) whites (non-Hispanic Caucasians), NM Hispanics, Puerto Rico (PR) residents by definition Hispanic, and US blacks. Among whites, the highest incidence was 8.0 per 100,000 and was ten times that of US blacks. The incidence among PR and NM Hispanic residents was 1.6 to 3.7 times that of US blacks. The anatomic distribution among NM Hispanics was similar to US and NM whites for both genders. In contrast, among PR residents the anatomic distribution in both genders was most common for the leg, similar to that for blacks. Spaniards who migrated to PR have more admixture with blacks from Africa than Spaniards who migrated to the mainland. This suggests a genetic predilection for the occurrence of melanoma on the lower extremity among PR residents as opposed to NM Hispanics.