The heart at necropsy in centenarians

Cardiac findings at necropsy are described in 6 patients aged 100 to 103 years of age. Although 4 had considerably narrowed coronary arteries at necropsy, none had apparent clinical evidence of myocardial ischemia or congestive heart failure during life.     

The clinical relevance of the Waterlow pressure sore risk scale in the ICU

OBJECTIVE: To evaluate whether the Waterlow pressure sore risk (PSR) scale has prognostic significance for intensive care patients. DESIGN: A prospective study. SETTING: The surgical intensive care unit (ICU) of the University Hospital Rotterdam. PATIENTS: Data were evaluated from 594 patients who had been admitted to the ICU during the year 1994. METHODS AND RESULTS: Each patient was assessed daily with respect to their Waterlow PSR score and the development of pressure sores in the sacral region. Actuarial statistical methods were used to analyse the predictive value of the risk score. When a patient had a Waterlow PSR score > 25 on admission, the risk of developing a pressure sore was significantly increased compared to patients with a PSR score < 25. After admission, the daily Waterlow PSR scores obtained were significantly associated with the risk of developing a pressure sore. For each additional point this risk increased by 23% (95% confidence interval 17 to 28%). CONCLUSIONS: The Waterlow PSR scale provides the medical and nursing staff at an early stage with reliable information about the risk patients have in developing a pressure sore.     

A prospective study of dietary fiber types and symptomatic diverticular disease in men

To examine prospectively dietary fiber calculated from food composition values based on analytic techniques and specific dietary fiber types in relation to risk of diverticular disease, we analyzed data from a prospective cohort of 43,881 U.S. male health professionals 40-75 y of age at base line; subjects were free of diagnosed diverticular disease, colon or rectal polyps, ulcerative colitis and cancer. The insoluble component of fiber was inversely associated with risk of diverticular disease relative risk (RR) = 0. 63, 95% confidence interval (CI), 0.44-0.91, P for trend = 0.02, and this association was particularly strong for cellulose (RR = 0.52, 95% CI, 0.36-0.75, P for trend = 0.002). The association between diverticular disease and total dietary fiber intake calculated from the AOACstandards method was not appreciably different from results using the Southgate or Englyst method [for AOAC method, RR = 0.60, 95% CI, 0.41-0.87; for Southgate method, RR = 0.61, 95% CI, 0.42-0. 88; for Englyst method, RR = 0.60, 95% CI, 0.42-0.87, for the highest quintiles]. Our findings provide evidence for the hypothesis that a diet high in dietary fiber decreases the risk of diverticular disease, and this result was not sensitive to the use of different analytic techniques to define dietary fiber. Our findings suggest that the insoluble component of fiber was significantly associated with a decreased risk of diverticular disease, and this inverse association was particularly strong for cellulose.     

Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: simultaneous determination by a high performance liquid chromatography with electrochemical detection

A simple, sensitive and accurate method for the simultaneous determination of risperidone (RSP) and its 9-hydroxy metabolite (9-OH-RSP) in human plasma is described. The relationship between dose of RSP and the plasma concentration of RSP and 9-OH-RSP in a clinical situation is discussed. Both compounds were isolated from plasma by a simple one-step liquid-liquid extraction with 15% methylene chloride in pentane. High-performance liquid chromatography separations were made on a cyano column and the compounds were detected by electrochemical detector. The method had sufficient sensitivity to determine RSP and 9-OH-RSP accurately at concentrations as low as 0.25 ng/ml when 1 ml of plasma is used for the analysis. The assay determinations were accurate, precise and consistent with a coefficient of variation less than 15%. Commonly co-administered drugs and other antipsychotics did not interfere with the analysis of either RSP or 9-OH-RSP There were large variations in inter- and intra-individual values of plasma concentrations of RSP and 9-OH-RSP. The 9-OH-RSP appears to be the major circulating active moiety and its plasma concentrations were, on the average 22 fold higher than that of RSP in schizophrenic patients treated with RSP. The ratio of RSP/9-OH-RSP concentrations suggested that three of the patients may have deficiency in cytochrome P450 enzyme CYP 2D6. The plasma concentrations of RSP showed a weak relationship with the administered daily oral dose (r = 0.4684, p = 0.01, n = 215). However, there was a good relationship between the daily dose of RSP and the plasma concentration of 9-OH-RSP (r = 0.6654, p = 0.01, n = 280) or the total active moiety, sum of RSP and 9-OH-RSP concentrations (r = 0.7041, p = 0.0005, n = 280). The measurement of the total active moiety in plasma of schizophrenic patients may be useful for assessing the relationship between dose and plasma concentration and dose and clinical outcome of patients rather than measuring RSP alone.     

Conduction properties of the crista terminalis in patients with typical atrial flutter: basis for a line of block in the reentrant circuit

INTRODUCTION: Previous mapping studies in patients with typical atrial flutter have demonstrated the crista terminalis to be a posterior barrier of the reentrant circuit forming a line of block. However, the functional role of the crista terminalis in patients with or without a history of atrial flutter is not well known. The aim of this study was to determine whether the conduction properties of the crista terminalis are different between patients with and those without a history of atrial flutter. METHODS AND RESULTS: The study population consisted of 12 patients with clinically documented atrial flutter (group 1) and 12 patients with paroxysmal supraventricular tachycardia as well as induced atrial flutter (group 2). A 7-French, 20-pole, deflectable Halo catheter was positioned around the tricuspid annulus. A 7-French, 20-pole Crista catheter was placed along the crista terminalis identified by the recording of double potentials with opposite activation sequences during typical atrial flutter. After sinus rhythm was restored, pacing from the low posterior right atrium near the crista terminalis was performed at multiple cycle length to 2:1 atrial capture. No double potentials were recorded along the crista terminalis during sinus rhythm in both groups. In group 1, the longest pacing cycle length that resulted in a line of block with double potentials along the crista terminalis was 638 +/- 119 msec. After infusion of propranolol, it was prolonged to 832 +/- 93 msec without change of the interdeflection intervals of double potentials. In group 2, the longest pacing cycle length that resulted in a line of block with double potentials along the crista terminalis was 214 +/- 23 msec. After infusion of procainamide, it was prolonged to 306 +/- 36 msec with increase of interdeflection interval of double potentials. CONCLUSION: The crista terminalis forms a line of transverse conduction block during typical atrial flutter. Poor transverse conduction property in the crista terminalis may be the requisite substrate for clinical occurrence of typical atrial flutter.     

Total-body and regional bone mineral content and areal bone mineral density in children aged 8-18 y: the Fels Longitudinal Study

We used a modification of the isolated perfused rat heart, in which coronary effluent and interstitial transudate were separately collected, to investigate the localization and production of angiotensin II (Ang II) in the heart. During combined renin (0.7 to 1.5 pmol Ang I/mL per minute) and angiotensinogen (6 to 12 pmol/mL) perfusion (4 to 8 mL/min) for 60 minutes (n=3), the steady-state levels of Ang II in interstitial transudate in two consecutive 10-minute periods were 4.3+/-1.5 and 3.6+/-1.5 fmol/mL compared with 1.1+/-0.4 and 1.1+/-0.6 fmol/mL in coronary effluent (mean+/-half range). During perfusion with Ang II (n=5), steady-state Ang II in interstitial transudate was 32+/-19% of arterial Ang II compared with 65+/-16% in coronary effluent (mean+/-SD, P<.02). During perfusion with Ang I (n=5), Ang II in interstitial transudate was 5.1+/-0.6% of arterial Ang I compared with 2.2+/-0.3% in coronary effluent (P<.05). The tissue concentration of Ang II in the combined renin/angiotensinogen perfusions (per gram) was as high as the concentration in interstitial transudate (per milliliter). Addition of losartan (10(-6) mol/L) to the renin/angiotensinogen perfusion (n=3) had no significant effect on the tissue level of Ang II, whereas losartan in the perfusions with Ang I (n=5) or Ang II (n=5) decreased tissue Ang II to undetectably low levels. The results indicate that the heart is capable of producing Ang II and that this can lead to higher levels in tissue than in blood plasma. Cardiac Ang II does not appear to be restricted to the extracellular fluid. This is in part due to AT1-receptor-mediated cellular uptake of extracellular Ang II, but our results also raise the possibility of intracellular Ang II production.     

Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia

We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.     

The interaction of thyroid state, MAOI drug treatment, and light on the level and circadian pattern of wheel-running in rats

In order to examine the relationship between thyroid status, the circadian system, and antidepressant drug response, the antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI), was administered chronically to sham-operated or thyroparathyroidectomized rats. Wheel-running was monitored continuously in a light-dark (LD) cycle, and then in constant dim light. In LD, MAOI treatment increased levels of running. This effect was delayed in hypothyroid rats relative to euthyroid rats. In constant light, the MAOI-induced increase in running was diminished in euthyroid but not hypothyroid animals. Hypothyroid animals were less responsive to the change in lighting than were euthyroid animals, and this was more apparent in hypothyroid rats given MAOI. The daily pattern of running differed with lighting condition as well as with treatment group. MAOI-treatment of hypothyroid animals phase-advanced the pattern of wheel-running. MAOI-treatment of control animals increased the amplitude of wheel-running particularly in the LD cycle. These results indicate that thyroid status, lighting, and MAOI treatment interact to alter the behavioral response to chronic drug treatment.     

Concurrent abomasal displacement and perforating ulceration in cattle: 21 cases (1985-1996)

OBJECTIVE: To evaluate the association of physical examination and clinicopathologic findings with surgical findings in cattle with concurrent abomasal displacement and perforating ulceration, to determine short- and long-term survival rates in these cattle, and to determine whether degree of peritonitis (focal vs diffuse) influences survival rates. DESIGN: Retrospective study. ANIMALS: 21 cattle with concurrent abomasal displacement and perforating ulceration and 42 cattle with uncomplicated abomasal displacement. PROCEDURE: Information on signalment, stage of lactation, physical examination findings, clinicopathologic data, surgical diagnosis, procedure(s) performed, and necropsy findings were retrieved from medical records of all cattle included in this study. Differences between physical examination findings of cattle with concurrent disease and those of cattle with uncomplicated displacements were evaluated, as were differences between survival rates in cattle with focal versus diffuse peritonitis. RESULTS: Cattle with concurrent disease had a greater probability of having pneumoperitoneum and signs of abdominal pain identified on physical examination than did cattle with uncomplicated diseases. There was no relationship between clinicopathologic data and survival time. Short-term survival rate was 38%, and degree of peritonitis significantly influenced survival time in cattle with concurrent abomasal displacement and perforating ulceration. Long-term survival rate in these cattle was 14%. CLINICAL IMPLICATIONS: Cattle with concurrent displaced abomasum and perforating ulceration have a poor chance for survival. In addition to detection of displaced abomasum, physical examination findings that can help lead to a presurgical diagnosis of this syndrome are pneumoperitoneum and signs of abdominal pain.     

Tibiofemoral contact pressures in degenerative joint disease

Using tibiofemoral joints from older (age, 53-80 years) human cadavers with articular cartilage degeneration, contact pressures and contact areas were measured in the extended knee in four conditions: (1) neutral alignment; (2) 5 degrees varus (simulating single limb stance of gait); (3) 5 degrees valgus; and (4) after a 5 degrees proximal tibial closing wedge valgus osteotomy. In degenerated cartilage, contact pressures were reduced at the lesion sites and were high on the borders of the lesions. No statistically significant changes occurred in contact pressures and areas when values from neutral loading were compared with values during loading in each of the other three conditions. Lateral average and maximum contact pressures were less in varus loading than in valgus loading. Equal medial and lateral contact pressures during varus loading, in contrast to lower medial than lateral contact pressures in the other three loading, supports the theory that the varus moment imposed on the knee in single limb stance could be a mechanism causing medial tibiofemoral osteoarthritis. The 5 degrees valgus osteotomy resulted in contact pressures similar to those in neutral loading. These experiments do not support the value of the 5 degrees valgus osteotomy in reducing contact pressures on the medial tibial plateau.