Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non-invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg-1 bodyweight min-1 enhanced the contractile state of the left ventricle without altering the heart rate.     

A biomechanical evaluation of the long stem intramedullary hip screw

Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon-a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon-a2b subcutaneously three times weekly for 12 months (5 MU/m2 for 4 months and then 3 MU/m2 for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV-RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/or virological relapse over the 6-month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon-a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric side effects.     

Effects of stress management on clinical outcomes in rheumatoid arthritis

An intriguing feature of early zygote development in Chlamydomonas reinhardtii is the active elimination of chloroplast DNA from the mating-type minus parent due presumably to the action of a zygote-specific nuclease. Meiotic progeny thus inherit chloroplast DNA almost exclusively from the mating-type plus parent. The plus-linked nuclear mutation mat3 prevents this selective destruction of minus chloroplast DNA and generates progeny that display a biparental inheritance pattern. Here we show that the mat3 mutation creates additional phenotypes not previously described: the cells are much smaller than wild type and they possess substantially reduced amounts of both mitochondrial and chloroplast DNA. We propose that the primary defect of the mat3 mutation is a disruption of cell-size control and that the inhibition of the uniparental transmission of chloroplast genomes is a secondary consequence of the reduced amount of chloroplast DNA in the mat3 parent.     

The management of atheromatous emboli to the lower extremities

Atheromatous emboli to the small vessels of the feet usually cause painful, cyanotic areas on the distal portions of the extremity. Complete resolution of the symptoms is the rule, and recurrent episodes are common. Atheromatous emboli to the major vessels of the leg often cannot be distinguished from emboli originating from other sources, unless characteristic gross or microscopic features are present in the embolous material. If the embolus contains atheromatous debris or if the origin is uncertain, aortic arteriograms are indicated to determine if an ulcerated lesion may have been the source. Apparently, two mechanisms of embolization exist; they are fragmentation with distal embolization of atheromatous material and embolization of plateletfibrin thrombus material from ulcerated plaques. Endarterectomy of the involved segment of aorta has been uniformly successful in preventing recurrent episodes of embolization.     

The effects of large doses of fentanyl and fentanyl with nitrous oxide on renal function in the dog

Renal effects of large doses of fentanyl (1 mg/kg) were determined in 14 mongrel dogs before and after addition of 50 per cent nitrous oxide. Fentanyl significantly increased urine osmolarity and decreased urine output and free water clearance but did not change inulin or PAH clearances. The arterial blood pressure and cardiac output were significantly decreased after 0.1 mg/kg fentanyl and these changes were then maintained during the remainder of the study period. Addition of nitrous oxide produced no further changes in cardiac output and arterial blood pressure but did increase urine output, PAH, inulin and free water clearances and decreased urine osmolarity. These data demonstrate that high doses of fentanyl have significant antidiuretic properties in the dog and these probably are related to the release of antidiuretic hormone. Our results also indicate that addition of nitrous oxide reverses fentanyl induced antidiuresis.     

Segmental calculus disease: potential of parital nephrectomy

Partial nephrectomy was performed on 71 renal units between 1962 and 1978 for segmental calculus disease. Parenchymal scarring associated with an infundibulocalyceal stone, which was usually branched, was the indication for resection. Stone analysis demonstrated an equal incidence of idiopathic and struvite stones. Perioperative morbidity was minimal, but pyelocutaneous urinary drainage prolonged the hospitalization of 5 patients. In 2 cases, the cause was an obstructing retained calculus. Retained calculi occurred in 3 other patients, one requiring early nephrectomy for sepsis. Fifty-seven patients were followed for longer than twelve months. Ipsilateral calculi recurred in 12 per cent of kidneys, and contralateral new calculi developed in the same number. Ninety-four per cent of patients with preoperative urinary tract infections had sterile urine at follow-up. From the results of this and other series, partial nephrectomy compares favorably with extended pyelolithotomy and anatrophic nephrotomy for segmental calculus disease associated with parenchymal scarring and/or a deformed collecting system.     

Thy-1, a novel marker for angiogenesis upregulated by inflammatory cytokines

We identified the cell surface glycoprotein Thy-1 on the endothelium of newly formed blood vessels in four models of angiogenesis in adult rats. Anti-Thy-1 staining showed that Thy-1 was upregulated in adventitial blood vessels after balloon injury to the carotid artery. Preabsorption with a rat Thy-1-Ig fusion construct eliminated all immunoreactivity and thus confirmed the specificity of the Thy-1 staining. Thy-1 was also expressed in the endothelium of small blood vessels formed after tumor implantation in the cornea, in periureteral vessels formed after ligation of the renal artery, and in small blood vessels of the uterus formed during pregnancy. In contrast with its expression during adult angiogenesis, Thy-1 was not expressed in the endothelium of blood vessels during embryonic angiogenesis. In vitro, the inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha upregulated Thy-1 mRNA by 8- and 14-fold, respectively. Vascular endothelial growth factor, basic fibroblast growth factor, transforming growth factor-beta, and platelet-derived growth factor-BB had no effect on Thy-1 mRNA. Thus, Thy-1 appears to be a marker of adult but not embryonic angiogenesis. The upregulation of Thy-1 by cytokines but not growth factors indicates the importance of inflammation in the pathogenesis of adult angiogenesis.