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Biomedical subjects

C J Carter

Publications and source records attributed to C J Carter.

119 records · Page 7Linked to original sources

The natural history and epidemiology of venous thrombosis.

Epidemiologic studies over the past 30 years have provided much of the basis for the understanding of venous thromboembolic disease. There has been an evolution from simple descriptive studies using clinical diagnosis to various forms of comparative studies using objective diagnoses. Identification of high-risk cases in the hospitalized population has led to the development of both general and specific antithrombotic prophylactic regimens. This has occurred against a background of an increased understanding of the pathophysiology of venous thrombosis. Inhospital case interventions have allowed direct questions concerning pathophysiology to be addressed. Examples would include the use of certain types and dosages of anticoagulants and the use of mechanical devices to avoid stasis. Despite these advances, there are still areas that require further attention. One aspect of importance is to evaluate the thrombotic risk of new procedures. The possibility that a new procedure may be either less or more thrombotic than its predecessor should be addressed. In the case of the former, additional antithrombotic measures are needed. An example of this is the relatively disappointing results of regular low-dose heparin treatment in some orthopedic procedures. In the case of the latter, less severe measures may be indicated. Current antithrombotic methods are not without risks and may not be necessary with some of the new endoscopic surgical procedures. Another area of importance relates to the monitoring of compliance. The information on antithrombotic methods has been available for two decades, yet surveys of the application of these methods consistently show that antithrombotic protocols are used less in North America relative to their use in equivalent institutions in Europe. A third area that still needs further epidemiologic study is the incidence and effects of venous thrombosis in the general community. Despite the two recent descriptive studies cited above, relatively little, as compared with the in-patient perspective, is known about community risk factors and their prevention. With respect to the natural history of hospital-based cases it seems unlikely that much is to be gained from surveying the efficacy of heparin or heparin-like treatment for mortality end points. However, a large and still unsatisfactorily examined area is the true frequency and impact of the postphlebitic syndrome. This aspect is germane to both hospital- and community-acquired DVT and, with an aging population, clearly deserves a lot more attention.

Epidemiologic Methods↗

Rapid fibrin D-dimer tests for deep venous thrombosis: factors affecting diagnostic utility.

Measurement of fibrin D-dimer may be a useful diagnostic test to exclude a diagnosis of deep venous thrombosis (DVT) in the emergency department setting. However, the specific assay format may influence its sensitivity and ultimate clinical utility. We tested samples from 200 patients under evaluation for DVT using three fibrin D-dimer assays: the SimpliRED whole blood agglutination assay, a latex agglutination assay, and the Dimertest EIA. Latex agglutination assays were performed in both a specialized laboratory and a routine laboratory. The negative predictive value for all tests was > 90%. The sensitivity of the SimpliRED assay was similar to that of the latex assay. The sensitivity of the latex assay was significantly lower when performed by generalist laboratory technologists. Thus, while D-dimer may be a useful test for the exclusion of DVT, subjective endpoint latex agglutination assays should be performed only by appropriately trained personnel.

Adolescent↗

Diabetic cystopathy presenting as primary acute urinary retention in a previously undiagnosed young male diabetic patient.

Lower genito-urinary problems are part of the polyneuropathy of diabetes. Cystopathy affects 40%-85% of diabetic patients, although less than half are symptomatic. We report on a 42-year-old patient who was not known to be diabetic, and who presented to the urologists with primary acute urinary retention. His underlaying disease was detected by a test for random blood glucose. More common causes were excluded with careful clinical and radiological examinations. He was managed with insulin and self-catheterization. Diabetes should be considered as a differential diagnosis in relatively young men who present with unexplained acute urinary retention.

Adult↗

Atypical perinuclear antineutrophil cytoplasmic antibodies after colectomy in inflammatory bowel disease.

A typical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) have been detected in most patients with ulcerative colitis and primary sclerosing cholangitis. Persistent atypical p-ANCA have been observed in ulcerative colitis patients with a prior proctocolectomy, especially with pouchitis, suggesting that this serological marker might be predictive of subsequent development of chronic or refractory pouchitis. This study prospectively evaluated this serological marker in 24 consecutive patients with inflammatory bowel disease and prior colectomies (12 with a clinical diagnosis of ulcerative colitis and 12 with a clinical diagnosis of Crohn's disease involving the colon). Of these, 14 were positive, including 11 with extensive ulcerative colitis and three with Crohn's disease. Although two of three ulcerative colitis patients with pouchitis were positive, eight of eight ulcerative colitis patients having a pelvic pouch with no] pouchitis were also positive, as was a patient who elected to have an end-ileostomy (Brooke's ileostomy). Two patients had abnormal liver chemistry tests. Both had end-stage primary sclerosing cholangitis treated with liver transplantation and were positive for this serological marker. Although atypical p-ANCA may be a marker of persistent inflammation in pelvic pouch patients, a positive test result should not be used for prognosis or as a decision-making parameter for pelvic pouch procedures.

Adolescent↗

Pharmacologic studies of cyclocytidine and arabinosylcytosine in dogs.

Cyclocytidine (cyclo-C) and arabinosylcytosine (ara-C) were compared as to distribution and metabolism in dogs after administration by the intravenous, subcutaneous, intramuscular, and oral routes. After cyclo-C, two metabolites were found in the plasma and urine--a hydrolytic product, ara-C, and its deaminated product, arabinosyluracil (ara-U). The urinary excretion of cyclo-C is rapid; Five hours after parenteral administration, 60% of the given drug is excreted; 45% as cyclo-C, 10% as ara-C, and about 5% as ara-U. In contrast, after similar injections of ara-C, 45% of the drug is excreted; 33% as ara-C and 12% as ara-U. When compared with those in human and mouse tissues, the deoxycytidine deaminase levels in dog tissues are extremely low. This agrees with the finding of low ara-U levels in dog plasma and urine after administering cyclo-C or ara-C. Regardless whether cyclo-C or ara-C is injected, the plasma decay curve of the resultant ara-C is biphasic, with calculated half-lives of 40 min and 2-2.5 hr. However, if ara-C is given, the plasma ara-C peak level is higher. Higher ara-C levels are also maintained throughout the measured 5 hr. There are no differences in pharmacologic disposition after iv, sc, or im administration of ara-C. This is also true for cyclo-C. These findings suggest that for both drugs, the above routes of administration may be equally effective. Neither cyclo-C nor ara-C is well absorbed after oral administration, and the drug concentration in the plasma is too low to be measurable. Whether the dog is fasted overnight or fed, the drug is excreted slowly. In 5 hr. no more than 3% is excreted, and by 12 hr. only 10% is excreted.

Administration, Oral↗

Distribution and inhibition of adenosine deaminase in tissues of man, rat, and mouse.

Adenosine deaminase activity, with arabinosyladenine (ara-A) used as the substrate, was measured in human leukemic cells and major tissues of man, rat, and mouse. The enzyme is stable in frozen tissues for at least 1 week, in frozen homogenate for several months, or after overnight dialysis at 4 degrees C in 0.25 M sucrose. The adenosine deaminase of chronic myelogenous leukemic (CML) cells has a Km of 0.6 mM and a Vmax of 183 mumols x 10(-2)/g of cells/minute. All species have highest activities in spleen and intestine. Kidney activity is highest in rat and lowest in man. The human brain has higher activity than the mouse or rat brain, and activity is higher in mouse liver than in human or rat liver. Activity in lung tissues is moderate and similar in all three species. The mean activity in CML cells is 195 mumols x 10(-2)/g of cells/minute, and the activity is higher in patients with CML in blast cell crisis. Acute myelogenous and lymphocytic leukemia cells also have very high activities. Drug concentrations required for inhibiting 50% of CML enzyme activity are 10 nM or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 0.6 nM of coformycin, and 0.3 nM of 2'-deoxycoformycin. Preincubation of the enzyme with coformycin, but not with EHNA, enhances the inhibition. In view of the high adenosine deaminase activities in tissues and the enhancement of the therapeutic effect of ara-A by inhibitors in mouse tumor systems, clinical trials of these combinations are warranted. They may be particularly beneficial to patients with CML in blast cell crisis.

Adenine↗