Preliminary characterization of the procoagulant material in human ascites

Disseminated intravascular coagulation invariably accompanies placement of peritoneovenous (LeVeen) shunts, which suggests that ascitic fluid contains procoagulant material capable of activating blood coagulation. In this study, we identified thrombogenic activity in human ascites and the hemostatic pathway by which it acts. Peritoneal fluid was removed percutaneously from patients with ascites due to various causes. Four fractions were prepared by centrifugation: cells, a low-speed, cell-free fluid, a high-speed supernatant, and the precipitate from the high-speed centrifugation. Cellular fractions from all ascitic fluids shortened a one-stage clotting time of normal pooled plasma by 68% in comparison with saline solution and endotoxin controls. Similarly, the cell-free fluids also shortened the clotting time of normal pooled plasma by 41%. The cellular and cell-free fractions shortened the clotting time of factor VIII-deficient plasma but failed to demonstrate procoagulant activity in factor VII-deficient plasma. These fractions had no effect on platelet aggregation or the platelet release reaction. The high-speed precipitate was dissociated by ethylenediaminetetra-acetate (EDTA) into fluid phase and precipitate, both of which demonstrated procoagulant activity. Furthermore, high-speed precipitate contained protein, phospholipid, and sterol in proportions similar to those of plasma membranes and contained membrane-bound vesicles as identified by means of electron microscopy. This material could be rendered inactive by heating to 100 degrees C for 2 minutes or by incubation with phospholipase C for 15 minutes. Finally, the ability of the high-speed precipitate to shorten the clotting time was prevented by preincubation with a monoclonal antibody, which is known to inhibit the procoagulant activity of human tissue factor. We suggest that several entities contribute to the procoagulant properties of human ascites, with procoagulant material deriving at least in part from peritoneal cells. The sedimentable procoagulant factor appears to be associated with cellular membranes or membrane fragments and is thromboplastin-like in its chemical composition, immunoreactivity, and substrate specificity.     

Teaching clinical research: what clinicians need to know

Clinicians are well suited in many ways to conducting research, but appropriate training and support must be provided. A series of multidisciplinary workshops designed to facilitate clinical research are used as a focus for describing common problems and their solutions. Practical means for initiating and assisting clinical research are proposed.     

Arthroscopic subacromial decompression. 1-3 year results]

In 148 patients with impingement lesion type I or type II, we performed an arthroscopic subacromial decompression (ASD). 122 patients ran a follow up one to three years post-operatively. All patients were pre- and postoperatively documented by a 100 point shoulder score. The mean score was 57.9 (+/- 11.5) preoperatively. Postoperatively there was a significant increase to 80.7 (+/- 17.9) (p < 0.05). 15% of the patients with a postoperative score less than 70 points were determined as failures. Patients with a preoperative pain history of more than one year had a significantly worse result (79.1 +/- 8.4) compared to those patients with a preoperative course less than one year (88.8 +/- 11.6) (p < 0.05). Other significant factors were the patient's age, and calcific tendinitis, whereas sex, preoperative range of motion, muscle atrophy, and degeneration of the acromioclavicular joint did not significantly influence the result. Our results after ASD in patients with subacromial pathology without a rupture of the rotator cuff are encouraging. Therefore, ASD seems to be a reasonable alternative to open acromioplasty.     

AIDS and South Africa--towards a comprehensive strategy. Part II. Screening and control

In this, the second of a three-part series of articles in which we propose steps towards a comprehensive strategy for the control of HIV infection, we consider controversies relating to screening for HIV, the indications for and desirability of mandatory testing of certain groups at risk, and the place of voluntary testing in the control of HIV transmission and infection. Key recommendations are that mandatory testing of donors of blood and other vital tissues, patients on haemodialysis and haemodialysis unit staff is justified, and that children put up for adoption may require testing. We make further recommendations regarding HIV testing as a prerequisite for life insurance and recommend that voluntary testing be offered, supported by adequate pre- and post-test counselling. We consider that all health care workers should accept as their moral obligation the care and management of HIV-infected individuals, and that they should be adequately educated and skilled in such work. These recommendations were reached largely by consensus, although there were occasions when individual authors condoned recommendations with which they did not personally agree.     

Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. We report here the clinical, endocrinological, and molecular analyses of two unrelated Japanese kindreds of 46,XX subjects affected with lipoid CAH who manifested spontaneous puberty. Phenotypic female infants with 46,XX karyotypes were diagnosed with lipoid CAH as newborns based on a clinical history of failure to thrive, hyperpigmentation, hyponatremia, hyperkalemia, and low basal values of serum cortisol and urinary 17-hydroxycorticosteroid and 17-ketosteroid. These patients responded to treatment with glucocorticoid and 9alpha-fludrocortisone. Spontaneous thelarche occurred in association with increased serum estradiol levels at the age of 10 and 11 yr, respectively. Pubic hair developed at the age of 12 yr 11 mo in one subject and menarche was at the age of 12 yr in both cases. Both subjects reported periodic menstrual bleeding and subsequently developed polycystic ovaries. To investigate the molecular basis of the steroidogenic lesion in these patients, the StAR gene was characterized by PCR and direct DNA sequence analyses. DNA sequence analysis revealed that one patient is homozygous for the Gln 258 Stop mutation in exon 7 and that the other patient is a compound heterozygote with the Gln 258 Stop mutation and a single A deletion at codon 238 in the other allele causing a frame-shift, which renders the StAR protein nonfunctional. These findings demonstrate that ovarian steroidogenesis can be spared to some extent through puberty when the StAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis which are characteristics of this disease.     

Silent and multiple mutations in p53 and the question of the hypermutability of tumors [published erratum appears in Carcinogenesis 1998 Jan;19(1):237]

Published data on TP53 mutations can be used to examine the question of whether generalized hypermutability is a necessary condition for tumorigenesis. Although individual mutations do play an etiologic role in tumor formation, the evidence so far does not make it necessary to assume a general mutability. Silent and multiple mutations in the TP53 data set indicate that a special hypermutability process operates on this gene during the generation of tumors. The percentage of silent p53 mutations observed (3%) is at least 20 times greater than would be expected and indicates hypermutability for this gene. The greater proportion of silent mutations among multiple p53 mutations (10%) indicates that the mutations occur nonselectively. The presence of silent mutations implies that not all mutations observed in tumors have an etiologic role. Analysis of the distribution of tumors with two, three, four and more p53 mutations suggests that mutations in some tumors occur in clusters possibly as a result of 'stuttering' in DNA synthesis. It is argued that the most likely alternative explanations of the data, polymorphism and/or a selective role for silent mutations, are not correct. It remains possible that the hypermutability process is restricted to particular genes or to regions of the genome as, for example, in antibody production. There is a surprising paucity of data on human polymorphism and nucleotide diversity which makes the analysis difficult.      

The conventional versus the new radiological contrast media. Cost-benefit analysis and medicolegal implications

New iodinated radiological contrast media, which are safer but much more expensive than the conventional ones, have been introduced. Since the financial implications are considerable a compromise between cost and safety is inevitable. It is therefore recommended that, at present, the conventional media be used routinely and the new media be reserved for potentially painful examinations and for patients at higher risk. Should a question of wrongfulness or negligence concerning the use of contrast media be considered by our courts, they will undoubtedly be influenced by what is considered 'common practice' and 'accepted practice' within a medical specialty and that may be co-determined by socio-economic considerations.     

Psychological moods and subjectively perceived behavioral and somatic changes accompanying anabolic-androgenic steroid use.

To assess physiological and psychological states accompanying anabolic-androgenic steroid use, male weight lifters 1) were interviewed regarding their physical training and the patterns and effects of any drug use; 2) completed a written physical and medical history questionnaire, a Profile of Mood States questionnaire, and the Buss-Durkee Hostility Inventory; and 3) were physically examined, including a blood sample and urinalysis. Subjects were divided into current anabolic-androgenic steroid users (N = 12), previous users (N = 14), and nonusers (N = 24). Current and previous users reported the following changes associated with anabolic-androgenic steroid use: increases in enthusiasm, aggression, and irritability; changes in insomnia, muscle size, muscle strength and density; faster recovery from workouts and injuries; and changes in libido. We were unable to confirm these interview and physical and medical history questionnaire responses using standardized and well-accepted psychological inventories. There were no significant differences among groups for any Profile of Moods factor, total mood disturbance, total Buss-Durkee Hostility Inventory score, or any subscale. For current users, there were no significant correlations between either total weekly drug dose or length of time on the current cycle of anabolic-androgenic steroids and any individual scale of the Profile of Mood States, Buss-Durkee Hostility Inventory, Profile of Mood States total mood disturbance, or composite Buss-Durkee Hostility Inventory score. Furthermore, anabolic-androgenic steroid users did not differ in their responses on these inventories from nonusers or from general population norms.(ABSTRACT TRUNCATED AT 250 WORDS)