Myocardial Demands of Atrial-Triggered Versus Fixed-Rate Ventricular Pacing in Patients with Complete Heart Block

Hemodynamics, myocardial oxygen consumption, and lactate concentration were determined by cardiac catheterization at rest and during exercise in eight patients treated with AV universal pacemakers (DDD) for high degree AV block. The pulse generator was alternately programmed in ventricular inhibited (VVI) or atrial synchronous (VAT) mode. During VVI pacing, the cardiac output rose between rest and exercise (4.3-7.6 L/min) due to increased stroke volume. VAT pacing gave significantly greater increase (4.5-8.8 L/min) which, as the stroke volume was unchanged, resulted from accelerated heart rate. The myocardial oxygen consumption and the coronary blood flow did not differ between VVI and VAT mode at rest or during exercise, nor did the modes make a difference in arterial systolic and pulmonary wedge pressures. These observations suggested that VAT pacing offers higher cardiac output than VVI pacing, but with similar demands on myocardial oxygen consumption.     

The critical C-terminus of the small subunit of herpes simplex virus ribonucleotide reductase is mobile and conformationally similar to C-terminal peptides

The C-terminus of the small subunit of class I ribonucleotide reductases is essential for subunit association and enzymatic activity. ¹H NMR analysis of the small subunit (2 × 38 kDa as a homodimer) of herpes simplex virus ribonucleotide reductase shows that this critical binding site is mobile and exposed in relation to the rest of the protein. Assignments of six C-terminal amino acids are made by comparing the TOCSY and NOESY spectra of the small subunit with the spectra of an identical protein truncated by seven amino acids at the C-terminus and the spectra of an analogous 15 amino acid peptide. The mobility of the C-terminus may be important for subunit recognition and could be general for other ribonucleotide reductases. The spectral comparisons also suggest that the six C-terminal amino acids of the small subunit and peptide are confor-mationally similar. This observation may be important for the design of inhibitors of ribonucleotide reductase subunit association. © Munksgaard 1994.     

Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer

Heat shock proteins (HSPs) protect cells against stress‐associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow‐up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence‐free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613–0.823 for intensity and 0.584–0.719 for IRp, but only 0.036–0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.     

CDTect-RIA AND CDTect-EIA FOR DETERMINATION OF SERUM CARBOHYDRATE-DEFICIENT TRANSFERRIN COMPARED

CDTect-RIA and CDTect-EIA for determination of serum carbohydrate-deficienttransferrin (CDT) by radioimmunoassay and enzyme immunoassayrespectively were tested for equality and precision in fourEuropean laboratories. For correlational studies, serum sampleswith CDT concentrations up to 130 U/1 were analysed in accordancewith a uniform trial schedule. The regression of CDT valuesobtained by the two procedures was computed for each laboratoryusing the method of Passing and Bablok. Slopes and interceptsof the regression functions did not differ significantly fromthe values 1 or 0, as proved by the corresponding 95% confidenceintervals. Precision studies were computed using analysis ofvariance. For CDT concentrations at the upper reference limitfor men, the within-day coefficients of variation (CVs) rangedbetween 0.7 and 6.4% (median 5.2%) for CDTect-RIA and from 4.3to 9.2% (median 6.2%) for CDTect-EIA. The corresponding purebetween-day CVs were 5.0–18.5% (median 9.8%) and 3.5–14.5%(median 10.9%). The study demonstrates the equality of CDT valuesobtained by CDTect-RIA and CDTect-EIA. According to this study,the two methods can be used interchangeably without gettingfluctuating CDT values, e.g. in longitudinal studies.     

Interstitial fluid volume,colloid osmotic and hydrostatic pressures in rat skeletal muscle. Effect of venous stasis and muscle activity

The effect of 24 h caval/iliac venous obstruction on interstital fluid volume (IFV), hydrostatic (P|) and colloid osmotic (COP₁) pressure in hindlimb skeletal muscle was studied in three groups of rats: Group I (GI), Intact innervation, unrestricted motor activity. Group II (GII), Sympathectomized, unrestricted. Group III (GIII), Motoric and sympathetic denervation + immobilization of the hindlimbs. Subcutaneous edema was present in all groups at femoral venous pressure (P_v) exceeding 13 mmHg. Skeletal muscle edema was seen in G III at P_v above 12 mmHg, in two rats in G II at P_v of 18 and 23 mmHg, but in no rats in G I. Whithout venous obstruction, control COP₁ was 8–10 mmHg in all groups. With increasing P_v, COP fell moderately in GI and GII: ΔCOP₁/AP_v= 0.22. In GIII, COP, fell from a control of 8.2 to 3.5 mmHg at a P_v of 12 mmHg (ACOP₁/AP_v=0.52), but remained constant with further rise in P_v P₁ was about 0 mmHg in controls and 1–2 mmHg in rats with muscle edema. IFV rose by 6% per mmHg increase in P_v in G III, and 2% in G I and G II. This expansion of IFV may explain about 70% of the fall in COP₁, the remaining being due to lymphatic washout of interstitial proteins. It is concluded that normal muscle activity together with dilution and washout of interstitial proteins constitute the main edema preventing mechansms in skeletal muscle.     

IS THERE ANY EVIDENCE FOR THE EXISTENCE HYPERTHYROID HEPATIC STATE FOLLOWING CHRONIC ALCOHOL INTAKE?

The hepatic concentrations of thyroid hormones were studiedin female Sprague-Dawley rats (N = 24) pair-fed nutritionallyadequate liquid diets containing either ethanol (36% of totalcalories) or isocaloric carbohydrates for 21 days. Comparedto controls, prolong4 alcohol consumption failed to result insignificant alterations of hepatic thyroid hormone levels (T₄:14.7 ± 1.81 ng/g of Liver wet weight vs 15.0 ±1.59; T₃: 2.60 ± 0.16 ng/g of liver wet weight vs 2.66± 0.18). Similar results were obtained when the hepaticlevels of thyroid hormones were expressed per total liver, perg of liver protein or per 100g of b d y weight. These data thereforeprovide no evidence for a ‘hyperthyroid hepatic state’following chronic alcohol consumption.