Increased Ca 2+-sensitivity of myofibrillar tension in heart failure and its functional implication

In human failing myocardium, an increased Ca ²⁺-sensitivity of myofilament tension development has been described in Triton X skinned cardiac myocytes compared to cardiomyocytes obtained from non-failing human donor hearts. The present study aimed to investigate whether there are functional implications of the increased Ca ²⁺-sensitivity in heart failure and whether alterations of myofilament function are already obvious at earlier stages of heart failure, such as in cardiac hypertrophy or whether alterations of the intracellular Ca ²⁺-homeostasis are able to induce alterations in myofilament function. Ca ²⁺-activated tension development was measured in Triton X-skinned fibers from human failing and non-failing myocardium. Ca ²⁺-sensitivity of myofilament tension development was significantly shifted to the left in human failing myocardium. Plots of diastolic free Ca ²⁺ versus diastolic tension development showed that in a range of similar diastolic Ca ²⁺-concentrations, diastolic tension was significantly enhanced in the failing hearts. The Ca ²⁺/tension relationship was shifted to the right in Triton X-skinned fiber preparations from transgenic renin overexpressing rats (TG(mREN2)27), shown to have concentric hypertrophy. In addition, the Ca ²⁺/tension relationship was unchanged in phospholamban knock-out mice with an increased systolic Ca ²⁺ (and enhanced diastolic Ca ²⁺-load). It is concluded that the increased Ca ²⁺-sensitivity of myofilament tension observed in single cardiomyocytes from failing human myocardium may be a phenomenon also present in multicellular preparations and may contribute to the diastolic dysfunction observed in human heart failure. Alterations of myofilament function occur at very early stages of heart failure and may be species dependent, or dependent on intracellular free Ca ²⁺-levels.     

13C/31P NMR studies of glucose transport in human skeletal muscle

The muscle intracellular (IC) free glucose concentration and the rate of muscle glycogen synthesis were measured by using in vivo ¹³C and ³¹P NMR spectroscopy in normal volunteers under hyperinsulinemic (≈300 pM) clamp conditions at the following three plasma glucose levels: euglycemia (≈6 mM), mild (≈10 mM), and high (≈16 mM) hyperglycemia. In keeping with biopsy studies, muscle IC free glucose concentration at euglycemia (−0.03 ± 0.03 mmol/kg of muscle, mean ± SEM, n = 10) was not statistically different from zero. A small but statistically significant amount of IC free glucose was observed during mild and high hyperglycemia: 0.15 ± 0.08 (n = 5) and 0.43 ± 0.20 mmol/kg of muscle (n = 5), respectively. Muscle glycogen synthesis rate, in mmol per kg of muscle per min, was 111 ± 11 at euglycemia (n = 10), 263 ± 29 during mild hyperglycemia (n = 5), and 338 ± 42 during high hyperglycemia (n = 5), these three rates being significantly different from each other. As previous in vitro and in vivo studies, these rates suggest a K_m (concentration at which unidirectional glucose transport reaches half-maximal rate) of the muscle glucose transport system in the 15–25 mM range under hyperinsulinemic conditions. The low concentrations of muscle IC free glucose observed under hyperinsulinemic conditions were interpreted, with this estimate and in the framework of metabolic control theory, as glucose transport being the predominant step controlling muscle glucose flux not only at euglycemia but also during hyperglycemia.     

Orthogonal leads for the measurement of QT dispersion: a comparison with conventional leads

To determine the characteristics of QT interval dispersion using orthogonal ECG leads with high paper speed (100 mm/s) and high voltage gain (10 cm/mV) as compared to conventional 12-lead ECG, we measured the QT dispersion in 57 patients at rest and directly after exercise using these two techniques. The measurements were repeated by the same observer and by an independent observer in 29 patients to assess reproducibility. QT dispersion was found to be significantly lower in orthogonal leads than standard lead tracings (24+/-20 ms versus 44+/-17 ms at rest, P<0.001; 29+/-21 ms versus 53+/-27 ms after exercise, P<0.001, respectively). The intrasubject and interobserver reproducibility was better for the orthogonal lead tracings, making this technique a potentially useful tool for future research.     

Falls in older Mexican-American women

OBJECTIVE: To determine the frequency of falls and identify risk factors for falls among older Mexican-American women. DESIGN: A prospective cohort study with an average follow-up of 2.7 years. SETTING: A clinical center at the Palo Alto Veterans Affairs Medical Center, California. PARTICIPANTS: 152 community-dwelling Mexican-American Caucasian women aged 59 years or older. OUTCOME MEASURES: Falls and injurious falls, as determined by monthly telephone interviews. RESULTS: The rate of falls was 508 per 1000 person-years (95% confidence interval (CI), 440-577). Injurious falls requiring medical attention occurred at a rate of 79 per 1000 person-years (95% CI, 52-107). Factors that were associated independently with an increased risk of falling were older age, a history of arthritis or rheumatism, a history of high thyroid, having fainted at least once in the year before baseline, current use of psychotropic medications, and walking fewer than 5 blocks a day. Those persons with an average time for the chair stand test had a lower risk of falling than those with the slowest times or the fastest times. CONCLUSIONS: The frequency of falls and injurious falls in this cohort of 152 relatively acculturated, healthy, older Mexican-American women was similar or slightly higher than previously reported rates for non-Hispanic Caucasian(s). Many of the factors associated with falls in this study were similar to those reported for non-Hispanic Caucasian women, suggesting that fall prevention measures tested mainly among non-Hispanic Caucasian women would also be appropriate for Mexican-American women.     

Cell-surface immunoglobulins in chronic lymphocytic leukemia and allied disorders

Immunoglobulin on the surface of peripheral blood lymphocytes from 57 patients with chronic lymphocytic leukemia (CLL) and allied disorders was investigated by fluorescence microscopy and correlated with circulating immunoglobulin. In 38 of 48 patients with CLL, the predominant surface immunoglobulin identified on peripheral blood lymphocytes was M (IgM) of either kappa or lambda light chain type. In five patients, the predominant surface protein was immunoglobulin G (IgG) of either kappa or lambda type. In three others, the lymphocyte surface immunoglobulin could not be definitely identified and in two, no surface immunoglobulin was detected. Circulating immunoglobulin levels, particularly IgM, were depressed in the majority of patients with CLL. In three subjects with IgM-bearing lymphocytes, the serum contained a circulating IgM M component and three of the five subjects with IgG-bearing cells, had a circulating IgG M component. In three patients with CLL, immunoglobulin disappeared from the cell surface with progression of the disorder, although neoplastic cells remained in the circulation. The amount of immunoglobulin on the surface of cells from patients with chronic lymphosarcoma cell leukemia was much greater than that on cells from patients with CLL, and the surface immunoglobulin pattern in hairy cell leukemia also appeared distinctive. Study of immunoglobulin on the surface of lymphocytes has helped to define the cellular origin and monoclonal nature of CLL, the source of circulating M components in this disease, and the relationship of CLL to other lymphoproliferative disorders. Although technically demanding, the study of surface immunoglobulin should prove useful in clinical medicine.     

Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy

In a prospective study abdominal paracentesis with ascitic fluid aspiration was performed in 54 consecutive patients with ascites of unknown cause. The ascitic fluid was examined cytologically and bacteriologically. The total cholesterol concentration was measured with an enzymatic colorimetric method. Malignant disease was diagnosed in 34 patients. Two of them had both malignant disease and liver cirrhosis and were excluded. Seventeen patients had liver cirrhosis, one had acute pancreatitis, and two had decompensated heart disease. The diagnostic value of an ascitic cholesterol concentration greater than 1.2 mmol/l in terms of predicting malignant disease was 87.5% (95% confidence limits, 71.0-96.5). The predictive value of an ascitic cholesterol concentration less than or equal to 1.2 mmol/l in terms of benign disease was 80.0% (95% confidence limits, 56.3-94.3). It is concluded that ascitic cholesterol measurement is a valuable supplement to cytologic examination in distinguishing between ascites of malignant and benign origin.