A clinical and experimental study of platelet function in chronic renal failure

Coagulation and platelet function studies were performed on 24 normal subjects and 29 patients with chronic renal failure due to various causes. Thrombocytopenia was uncommon in the uraemic patients but there was reduced platelet retention in glass bead columns and platelet aggregation with adenosine diphosphate (ADP) and thrombin was slower and less complete than normal. The rate of platelet disaggregation in uraemic patients was significantly reduced. The abnormalities tended to be more severe in more uraemic subjects. In normal subjects no inter-relationships were observed between the various measurements of platelet activity. In patients there were significant interrelationships between the measurements of platelet aggregation with ADP and thrombin and between the measurements of aggregation and retention in glass bead columns. It is suggested that if a common pathway is involved in these reactions it is adversely affected in uraemia.Plasma coagulation defects were uncommon and present in only five of the uraemic subjects. Impaired prothrombin consumption apparently due to defective platelet function was present in half the patients but was not detected by a kaolin activation method. Although platelet coagulation function was activated during ADP aggregation and disaggregation in normal and uraemic subjects, it did not correlate in the latter with impairment of aggregation. It is suggested that aggregation and activation of platelet coagulant activity are not necessarily related aspects of platelet function. An effect of uraemic plasma on normal platelets was demonstrated by mixing experiments consistent with a humoral cause for the uraemic platelet defects.     

Application of 1H nuclear magnetic resonance spectroscopy to the analysis of beta-lactam antibiotics and their common degradation products

The (1)H NMR characteristics of the majority of penicillin and cephalosporin beta-lactam antibiotics in world-wide clinical use are presented. Some of the data are novel and include several high resolution (220, 400 MHz) spectra. The influence of solvent and ionisation state upon spectral parameters is discussed and a scheme of analysis proposed for identifying an unknown beta-lactam sample. Spectral features of common degradation products of benzylpenicillin and other penicillins are provided and the use of (1)H NMR spectroscopy in monitoring the breakdown of penicillin antibiotics described. Other aspects discussed are NMR studies of the stereochemistry, association and protein binding of beta-lactam antibiotics.     

Clinical comparison of freeze-dried and fresh frozen patellar tendon allografts for anterior cruciate ligament reconstruction of the knee

The aim of this study was to evaluate the clinical outcome of freeze-dried compared to fresh frozen allograft tissue used as a substitute for a ruptured ACL of the knee. In addition, the incidence of any graft rejection phenomena was recorded. Forty-one patients with ACL deficient knees underwent reconstructive surgery using a patellar bone-tendon-bone allograft that had been freeze-dried (Group 1, N = 14) or fresh frozen (Group 2, N = 27). All patients underwent the same implant technique and rehabilitation program. Followup ranged from 24 to 36 months. The evaluation consisted of subjective, objective, and instrumented laxity testing (KT-1000, MEDmetric, San Diego, CA; and Genucom, FARO Medical Technologies, Inc., Montreal, Canada). There were 31 males and 10 females. Eleven (79%) patients in Group 1 thought their knee was "normal" or "improved," and 25 (93%) in Group 2 thought the same. In addition, 10 (71%) patients in Group 1 denied any "giving way," compared to 26 (96%) in Group 2. The mean Lysholm knee score in Group 1 was 86/100 (range, 22 to 100) compared to 92/100 (range, 59 to 100). Clinical examination included the Lachman test and tests for anterior drawer sign and pivot shift. Postoperatively, Group 1 patients had the following results: Lachman test--seven Grade 0, six Grade 1, one Grade 2; anterior drawer sign--eight Grade 0, five Grade 1, one Grade 2; and pivot shift--seven Grade 0, five "trace," and two "present."(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistence of tolerance to effects of cocaine on schedule-controlled behavior in pigeons

Keypecking by seven pigeons, maintained by a fixed-ratio 30 schedule of food presentation, was decreased in rate by acute pre-session administration of cocaine. In Part 1 (four pigeons), tolerance to the rate-suppressing effects of cocaine developed during daily administration conditions. Tolerance persisted (1) when daily cocaine injections were replaced by conditions in which cocaine was administered every other day, then every fourth day, then every eighth day, then every 16th day, with all intervening sessions preceded by saline injections and (2) when daily cocaine administration was replaced abruptly by a condition in which cocaine injections were spaced 16 days apart, with all intervening sessions preceded by saline. In Part 2 (three pigeons), tolerance developed during intermittent administration conditions (e.g. cocaine injected every eighth day) for two subjects, and during daily administration for the third subject. As in Part 1, tolerance persisted when cocaine was administered only once every 16 days. These results are consistent with an interpretation of tolerance based upon operant compensatory reactions to drug-induced behavioral disruptions and suggest that a simple associationist model of tolerance to cocaine-induced response-rate suppression may be inadequate. The data also have practical implications regarding tolerance development during intermittent administration conditions similar to conventional acute dose-effect determination procedures.     

Blood pressure responses to acute static and dynamic exercise in three racial groups

PURPOSE: African Americans have a higher incidence of hypertension than other racial groups. Furthermore, some research suggests that normotensive individuals who exhibit exaggerated blood pressure (BP) responses to exercise may be at risk for future hypertension. This study sought to determine whether normotensive African Americans exhibited exaggerated BP responses to static exercise or dynamic exercise relative to Caucasian Americans and Asian Americans. METHODS: Thirty normotensive subjects participated from each of the three racial groups (15 men and 15 women). Subjects held 30% of maximal voluntary contraction (right knee extension) for 3 min, and BP was recorded during the 3rd min. On a separate occasion, subjects cycled for six min at a power equivalent to 70% of VO2 reserve, and BP was recorded during the 6th min. RESULTS: Static exercise produced large, significant increases in both systolic and diastolic BP (35 +/- 1.5 and 29 +/- 1.3 mm Hg, respectively). Dynamic exercise produced large, significant increases in systolic BP (51 +/- 1.6 mm Hg) and moderate, yet significant, increases in diastolic BP (8 +/- 1.0 mm Hg). There were no significant differences between racial groups in BP response to either static exercise or dynamic exercise. However, during dynamic exercise, men had a higher systolic BP response than did women. CONCLUSIONS: African Americans who are normotensive at rest do not exhibit a greater BP response to static exercise or dynamic exercise than do Caucasian Americans or Asian Americans.     

Effectiveness of antipsychotic therapy in a naturalistic setting: a comparison between risperidone, perphenazine, and haloperidol

BACKGROUND: Therapeutic ineffectiveness and noncompliance with antipsychotic agents are major contributors to rehospitalization in patients with psychotic disorders. It is unknown whether risperidone's favorable side effect profile compared with that of the conventional antipsychotics results in improved compliance and reduced hospitalizations in a naturalistic setting. The purpose of this study was to test the hypothesis that treatment with risperidone reduces readmission rates and associated costs when compared with treatment with perphenazine or haloperidol. METHOD: Inpatients prescribed either risperidone, perphenazine, or haloperidol between January 1, 1995, and December 31, 1995, as a single oral antipsychotic at discharge were retrospectively identified. Data were collected for that index hospitalization and for a 1-year follow-up period. Primary outcome measures included re-admission rates, changes in antipsychotic therapy, anticholinergic drug use, and costs. RESULTS: There were 202 evaluable patients (81 treated with risperidone, 78 with perphenazine, and 43 with haloperidol). Baseline demographics were similar between groups except that more patients in the risperidone group had a primary diagnosis of psychotic disorder or had been hospitalized in the year prior to study. The percentage of patients readmitted during the 1-year follow-up period was similar among drug groups (41% risperidone, 26% perphenazine, and 35% haloperidol) when controlled for baseline differences in diagnosis and hospitalization history (p = .32). Anticholinergic drug use was more common in the haloperidol group (p = .004). Mean yearly cost (drug + hospitalization) in the risperidone group was $20,317, nearly double that in the other treatment groups (p < .001). CONCLUSION: The results from this naturalistic study indicate that the high cost of risperidone is not offset by a reduction in readmission rates when compared with conventional antipsychotics.     

Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment.

OBJECTIVE: We attempted to compare the use of low-dose heparin with a standard dose of 40 mg prednisone daily (both plus low-dose aspirin) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death. STUDY DESIGN: A multicenter randomized trial included 20 patients. Generalizability of results from randomized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for randomization. Data from study groups were compared with Fisher's exact test, and generalizability was evaluated with a chi 2 test for trend. RESULTS: Live birth rates were the same (75%) with either treatment, but "serious" maternal morbidity and the frequency of preterm delivery were significantly higher among women randomly assigned to prednisone (p = 0.02 vs p = 0.006). Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia. These results could be generalized to the other groups of women ascertained during the course of the study. CONCLUSIONS: Low-dose heparin should be preferred to prednisone when treatment is indicated for high-risk pregnant women with antiphospholipid antibodies.