Moxalactam, bleeding, and renal insufficiency.
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Biomedical subjects
Publications and source records attributed to D G Miller.
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Nine azotemic patients who developed a coagulopathy associated with the use of either cephalosporin or moxalactam antibiotics are reported. The acute renal failure patients had neoplastic disorders and were considered to be septic at the time that multiple antibiotics were administered. Four of 5 chronic hemo- or peritoneal dialysis patients also received multiple antibiotics. Nevertheless, the coagulopathy seemed to be most closely associated with the administration of the cephalosporin. One patient received moxalactam as part of the combination therapy for diffuse pulmonary infiltration during renal transplant rejection. Bleeding occurred into the gastrointestinal tract in four patients, into the kidney-urinary tract in three patients, into vascular surgical sites in two patients, and one each into the pulmonary-bronchial and cerebral-ventricular systems. Five operations were performed in four patients: a nephrectomy for massive subcapsular hemorrhage with a prothrombin time that exceeded 100 seconds; arteriovenous graft complicated by post-operative bleeding associated with prolongation of the prothrombin time; elective femoral-popliteal bypass complicated by a prolonged prothrombin time, bleeding into the graft site, hypotension, and a subendocardial myocardial infarction; elective cholecystectomy complicated by a two unit bleed associated with a slightly prolonged prothrombin time, followed by elective femoral-popliteal bypass complicated by a fatal intercerebral bleed associated with a more than twice normal prothrombin time. Cephalosporins are most likely associated with Vitamin K deficiency. Moxalactam is more likely to be associated with platelet dysfunction. Monitoring of the prothrombin time for cephalosporins or the bleeding time for moxalactam is the most reliable way to prevent what may be rapid emergence of clinical bleeding in patients with renal failure.
Peripheral resting mononuclear leukocytes were compared for their capacities to repair DNA lesions induced by a 1-hour exposure to a standardized 10-microM dose of N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). Leukocytes from the following 3 groups were studied: 39 control subjects, 40 patients after colonic resection because of colorectal cancer (disease-free at the time of this study), and 28 individuals with a hereditary predisposition to colorectal cancer. Although the level of N-AcO-2-FAA that bound to mononuclear leukocyte DNA was the same for the various population groups, the level of N-AcO-2-FAA-induced unscheduled DNA synthesis (UDS) was significantly reduced in the mononuclear leukocytes of individuals who had had colorectal cancer or a genetic predisposition for the disease. These findings indicate that a deficiency in mononuclear leukocyte DNA repair synthesis is associated with the development of colorectal cancer in these populations. Our observation of this nonspecific UDS deficiency (relating to colorectal cancer) was not explained by experimental variations among the sampled groups with regard to individual differences in lymphocyte heterogeneity, age, sex, smoking habits, or blood pressure.
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Four insulin-dependent diabetics became insulin-independent sometime after beginning maintenance dialysis for renal failure. Spontaneous hypoglycemia occurred after insulin was discontinued in two individuals treated with peritoneal dialysis. Although weight loss was significant in each, three of the four maintained ideal body weight. By diminishing the insulin resistance of uremia, dialysis may play an active role in promoting the metabolic effect of endogenous insulin even in diabetics with multiple complications of hyperglycemia.
Screening for the early detection of cancer offers the potential of increasing the number of patients whose cancer is diagnosed in a localized, curable stage. The operation of an efficient and effective early detection program requires that a number of conditions be fulfilled, some of which are difficult to attain. First, the target population for screening should be defined demographically and epidemiologically so that the screening program is designed to be responsive to the needs of that group, e.g., age, ethnic composition, special occupational or environmental circumstances. Furthermore, an appropriate means of communicating with the reference population must be established so that the group can be educated regarding cancer prevention and detection and motivated to use early detection programs. Screening for early detection should be carried out on two levels: primary screening for the identification of risk factors, and prescriptive screening for additional procedures ordered according to the patterns of risk factors, and prescriptive screening for additional procedures ordered according to the patterns of risk factors identified. The screening encounter should be an opportunity for health education regarding primary prevention, as well as early detection of cancer. Screening without follow-up for diagnosis and treatment is likely to be counterproductive; the patient must be provided with a means of entering the health care system when this is indicated by the screening examination. Follow-up of suspicious findings must also be carried out for end-result evaluation. Primary screening can be carried out successfully by allied health personnel under most circumstances. A program employing these principles is now being utilized by a number of independent clinics in a voluntary collaborative program called "CANSCREEN." Examples of the operational modes of this program will be presented.
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Since insulin enhances the catabolism of low-density lipoprotein (LDL) by cultured human cells, a potential role of insulin in the regulation of plasma LDL levels in man is suggested. To evaluate the possible effect of insulin on LDL catabolism in vivo, the disappearance rates of injected 125I-labeled autologous LDL were determined before and after endogenous hyperinsulinemia was evoked by total parenteral nutrition. Multicompartmental analysis of plasma decay curves showed a 26% increase in the fractional catabolic rate of LDL after total parenteral nutrition was started. An associated reduction of plasma cholesterol levels resulted from changes in both LDl and high-density lipoprotein. These results suggest that the reduction of LDL levels during total parenteral nutrition is at least partly accounted for by enhanced LDL catabolism. It is postulated that the enhanced LDL catabolism may result from the hyperinsulinemia that accompanies total parenteral nutrition, via insulin stimulation of receptor-mediated LDL catabolism.
We reviewed our experience with 43 consecutive patients who underwent operations for postinfarction ventricular septal defect to determine optimal time for operative intervention, to identify factors responsible for failure of operative treatment, and to determine long-term survival rates. Patients were referred for operation after expectant medical management had failed or after 6 weeks electively. The operative mortality rate was 42% and ranged from 90% for those who required operation within 1 day of 11% for those underwent surgery after 1 month. In a multivariate discriminant analysis of preoperative variables, we found that inferior infarction with perforation (P less than 0.02) and preoperative multisystem failure (evidenced by abnormal mental status, P less than 0.02) were the major factors correlating with high operative risk. Early operation per se did not affect operative mortality rates. Technical problems with early operation were not a source of major morbidity and mortality. Actuarial long-term survival was good, and 88.5% of survivors were alive 5 years after surgery. Because preoperative multisystem failure is often progressive, we recommend immediate operation for all patients with postinfarction ventricular septal defect unless no deterioration is present. Moreover, because of the high risk of those patients with inferior infarction and perforation, we recommended immediate surgery for this group regardless of symptomatic status.
The most prominent factor determining susceptibility to cancer is age. However, there is little evidence that the aging process per se increases susceptibility to cancer. Rather, age provides the time necessary for the accumulation of cellular events required for the development of neoplasia. The variations in the patterns of cancer incidence rates seen with age can be explained by alterations in conditions of exposure to carcinogenic stimuli. There is no evidence that the pool of susceptible individuals in a population is limited. Cancer occurs as a random event in a population with greater or lesser frequency according to the presence of risk factors. In populations with an increased frequency of cancer such as those with genetic abnormalities, immune deficiency syndromes, or altered hormonal states, the risk of developing cancer is never generalized to all tissues but is characteristic of particular tissues at risk. Any circumstance of internal or external origin that disturbs homeostasis of particular tissues at risk. Any circumstance of internal or external origin that disturbs homeostasis over a prolonged period of time increases the susceptibility to cancer for the tissue concerned. Susceptibility to cancer does not mean that cancer is inevitable. Only a small number of those susceptible to cancer by virtue of a special risk factor develop the disease. Furthermore, most patients who develop cancer have no determinable risk factors. Although all evidence points to a multifactorial, multistage process, the rate of somatic mutation appears to be the key determinant factor in susceptibility to cancer. This concept is supported by research studies showing that the onset of atherosclerosis is initiated by somatic mutations, and the finding that the same chemical mutagens can advance the development of both diseases.
Our controlled trial of screening for colorectal cancer has now been in progress for almost five years. Screening is accomplished by rigid sigmoidoscopy in control and study groups and, in addition, by fecal occult blood testing in the study group. Patients screened are men and women age 40 and older, mostly at average risk. Fecal occult blood testing is with Hemoccult slides with patients on a meat-free, high-bulk diet without hydration, and with a four-day storage interval between slide preparation and testing. Patients with positive slides undergo diagnostic investigation that includes both colonoscopy and double-contrast barium enema and, in some, an upper gastrointestinal series. Preliminary results to date include: patient baseline statistics and subgroup comparability, rate of positive slides of 1-4%, predictive value for neoplasia of 44-50%, false-positives of 0.5-2.1%, favorable Dukes' staging of cancers in the study group, and high patient compliance. Considerably more follow-up is need in our study and control population, and issues such as mortality and cost need to be addressed. Additional time will be necessary to provide firm conclusions.
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In 94 patients, 137 permanent Silastic central venous catheters were inserted. Of these, 53 catheters were removed because of catheter related problems. The average duration of catheter use was 12 months. However, the catheter was only removed once every 31 patient months because of catheter dysfunction and once every 82 months because of catheter related sepsis. None of the patients died from catheter related septicemia. We believe this low complication rate of catheter related complications represents an acceptable risk for those patients who will benefit from home parenteral nutrition.
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