Anti-thrombotic therapy for non-rheumatic atrial fibrillation

Recent randomized trials of antithrombotic therapy in non-rheumatic atrial fibrillation have helped to clarify the benefits of warfarin and aspirin. Low-risk patients (normotensives aged <60 with normal left ventricular function) have a small risk of thromboembolic events and are unlikely to benefit significantly from anticoagulants, but may benefit from aspirin with little increase in risk of bleeding. High-risk patients (>75 years, impaired left ventricular function, previous thromboembolism and/or associated conditions such as hypertension and diabetes mellitus) have an increased risk of thromboembolism, and benefit from long-term anticoagulant therapy to a greater degree than with aspirin, although at a risk of increased bleeding complications.      

Dependence of deoxycorticosterone/salt hypertension in the rat on the activity of adrenergic cardiac nerves.

1. Chronic hypertension was induced in Wistar rats with intact kidneys by subcutaneous implantation of 50 mg of deoxycorticosterone acetate (DOCA) in wax and addition of sodium chloride (9 g/l) to the drinking water. 2. The development of DOCA/salt hypertension, as monitored by tail-cuff plethysmography, was prevented by: (a) destruction of the peripheral adrenergic nerves with neonatal administration of guanethidine (80 mg/kg subcutaneously for the first 14 days postnatally); (b) bilateral stellate ganglionectomy; (c) oral administration of the beta-adrenoreceptor antagonists propranolol or atenolol (1 mg day-1 kg-1) during the period of DOCA/salt treatment. 3. The dose of DOCA used was sufficient to inhibit the atrial Uptake2 pathway completely: this process appears to participate in termination of action of neurally released noradrenaline in the heart. 4. It is suggested that this model of DOCA/salt hypertension is due to adrenergic enhancement of cardiac output in the presence of an increased sodium load. The enhancement may be partly due to deficient myocardial inactivation of noradrenaline.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

The pharmacology of a new pasteurized antihemophilic factor concentrate derived from human blood plasma

The pharmacology of a new pasteurized factor VIII (FVIII) concentrate derived from human blood plasma was studied in 23 adults with hemophilia A. In Part 1 of the study involving six nonbleeding subjects, the mean increase in FVIII activity was 1.43 +/- 0.34 U per ml 10 minutes after an intravenous dose of 50 U per kg. The intravascular survival kinetics in these six patients showed a biphasic decay curve with an initial mean half-life of 5.1 +/- 1.2 hours probably representing early redistribution, and a late half-life of 13.3 +/- 4.9 hours. In Part 2 of the study, the activity at 10 minutes was measured in another 17 patients, as well as in one patient already studied in Part 1. The mean increase in activity with the 24 observations was 1.13 +/- 0.37 U per ml with a mean FVIII dosage of 51.0 +/- 2.6 U per kg of body weight. Only one patient had an allergic reaction, which did not recur when the patient was given a second lot.     

In vitro and in vivo activity of murine lymphokine-activated killer cells after cryopreservation

The in vitro and in vivo effects of cryopreservation on the cytotoxic activity of murine lymphokine-activated killer (LAK) cells were studied. LAK cells were generated by incubation of spleen lymphocytes of BALB/c mice for 3 days with recombinant interleukin-2 (rIL-2) and subsequent cryopreservation. Cytotoxicity was determined in a 51Cr release assay. After thawing, cytotoxic activity was reduced (40.4% 51Cr release at an effector:target cell ratio of 40:1 as compared to 68.5% 51Cr release before freezing) and could be restored to precryopreserved levels by reincubation with rIL-2 for 2 days after thawing (78.8% 51Cr release). These cells were then tested in BALB/c mice injected with RAW 112 cells, a pre-B-cell lymphoma line. The results demonstrate that the survival rate of mice injected with cryopreserved and restimulated LAK cells (50% survival greater than 180 days after injection) did not differ significantly from that of mice injected with fresh unfrozen LAK cells (60% survival greater than 120 days, 50% survival greater than 180 days). Cryopreserved LAK cells have potential use in adoptive immunotherapy.     

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

Profile analysis: detection of distantly related proteins.

Profile analysis is a method for detecting distantly related proteins by sequence comparison. The basis for comparison is not only the customary Dayhoff mutational-distance matrix but also the results of structural studies and information implicit in the alignments of the sequences of families of similar proteins. This information is expressed in a position-specific scoring table (profile), which is created from a group of sequences previously aligned by structural or sequence similarity. The similarity of any other sequence (target) to the group of aligned sequences (probe) can be tested by comparing the target to the profile using dynamic programming algorithms. The profile method differs in two major respects from methods of sequence comparison in common use: (i) Any number of known sequences can be used to construct the profile, allowing more information to be used in the testing of the target than is possible with pairwise alignment methods. (ii) The profile includes the penalties for insertion or deletion at each position, which allow one to include the probe secondary structure in the testing scheme. Tests with globin and immunoglobulin sequences show that profile analysis can distinguish all members of these families from all other sequences in a database containing 3800 protein sequences.     

A fuzzy logic model for differential diagnosis of lower urinary tract dysfunctions

Lower urinary tract dysfunctions (LUTD) restrict quality of life, resulting in decreased work productivity and emotional well‐being. However, most people are not diagnosed because they do not seek medical treatment. In addition, some facilities do not adequately train health professionals in the evaluation, diagnosis and treatment of these conditions. The study's objective was to develop a decision support system modelled on fuzzy logic that defines LUTD using the terminology of the International Continence Society. This methodological study aimed to develop a model that uses the maximum–minimum composition (max–min) of fuzzy relations that can perform differential diagnoses of LUTD. The model was tested in 100 cases (50 men and 50 women), and the data were obtained from medical records containing the clinical data and results of urodynamic studies. All medical records were reviewed by a specialist in urology. The model was capable of determining a diagnosis in full (62%) or partial (36%) agreement with the medical report. Agreement between the model and the medical report was excellent (kappa = 0·98, p ? 0·001, CI = 0·88–1) or substantial (kappa = 0·53, p ? 0·001, CI = 0·45–0·60), considering overestimative accordance (where accordance is assumed when at least one diagnosis is equal) and underestimative accordance (where accordance is assumed when all diagnoses are equal), respectively. The proposed model based on the max–min composition of fuzzy relationships is very simple and performed well. However, more tests are recommended before the model is used as a decision support system.