Focal endemic coccidioidomycosis in Los Angeles County.
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Biomedical subjects
Publications and source records attributed to J L Robinson.
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A partial deficiency of UMP synthase has been detected in Holstein dairy cattle. Since affected females secrete milk with elevated concentrations of orotate, milk orotate was used to screen for the condition among 880 cows in 17 randomly selected Holstein herds in Illinois. Mean orotate was 85.0 +/- 1.5 microgram/ml milk and 17 cows had milk orotate in excess of 170 micrograms/ml. Including the latter animals, 42 cows were evaluated for erythrocyte UMP synthase and 15 were found to be partially deficient. Thus, at least 1.7 percent of all cows had the condition; this is a minimal estimate because the initial screen was milk orotate and this may be low, particularly early in lactation. Deficient cows had half the level of UMP synthase as normal, nondeficient cows (1.30 +/- 0.06 vs. 2.79 +/- 0.10 units/ml). The binomial classification of deficient versus normal accounted for 72 percent of the variation noted in UMP synthase. Milk orotate was significantly elevated in deficient cows (337.8 +/- 31.3 micrograms/ml), validating its use as a screening device. Urinary orotate also was higher for deficient cows (28.4 +/- 5.2 vs. 9.2 +/- 0.8 micrograms/ml) and differentiated the two groups as well as milk orotate. Normal and deficient cows did not differ in milk lactose concentrations. Erythrocyte UMP synthase also was measured in 85 Holstein bulls used for artificial insemination and 6 had low levels of UMP synthase (1.39 +/- 0.19 vs. 2.92 +/- 0.05 units/ml); the binomial classification accounted for 42 percent of the variation. The partially deficient animals identified appear to be heterozygotes for a condition expected to be lethal in the homozygous state.
The inheritance of uridine-5'-monophosphate (UMP) synthase in dairy cattle was consistent with a two-allele, single-autosomal-locus model. Two phenotypes were associated with different levels of the enzyme in bovine erythrocytes. The predominant phenotype (assumed normal) had twice the concentration of UMP synthase as the second phenotype (deficient). A one-to-one correspondence between enzyme level and genotype identified one homozygote as normal, the heterozygote as deficient, and the other homozygote as unobserved. Three alternative hypotheses were rejected. The deficiency as homozygous recessive was rejected because 20 matings between assumed normal males and deficient females resulted in 10 normal and 10 deficient offspring. The hypothesis that the deficiency was homozygous dominant was rejected because the 95 percent confidence interval about the observed gene frequency, 0.0024 to 0.0146, did not contain the estimated gene frequency for equilibrium between an average 10(-5) mutation rate and selection against the deficiency as homozygous dominant. Analyses of female relatives implicated one bull as deficient (96 percent probability), as he had, independently, 2 deficient daughters, 5 deficient granddaughters from untested dams, and 3 deficient great-granddaughters from untested ancestors. The hypothesis that the deficiency was sex-linked was rejected because 3 of 9 tested sons of the putative deficient bull were deficient. Calf mortality is expected in 25 percent of matings between deficient animals.
In vivo studies have begun to evaluate a new intraventricular electric axial flow left ventricular assist device (LVAD), the Jarvik 2000, which is a small, valveless pump that is placed inside the left ventricle through the left ventricular apex. The operation, which is performed through a left thoracotomy, may be done without cardiopulmonary bypass and aortic cross-clamping. Outflow is provided through a 16 mm softly woven, Dacron graft anastomosed to the descending thoracic or abdominal aorta. Pump flow, which varies from 2 to 16 l/min in vitro, is changed by adjusting the speed of pump rotation. Preliminary studies were done to evaluate the ease of implantation, hematologic and anatomic compatibility, and pump performance. The device has been implanted in seven healthy, preconditioned calves (83-138 kg), one of which is currently undergoing support. The implantation procedure averaged 3 hours. There were no operative deaths, and blood transfusions were not required. Postoperatively, anticoagulation was achieved with heparin followed by warfarin sodium to maintain prothrombin time or partial thromboplastin time at 1.5-2.0 times baseline. In the six completed studies, support time ranged from 2 to 120 days (mean, 36 days). The seventh calf has been supported for 30 days. In the four long-term studies (20, 70, 120, > 30 days), the mean plasma free hemoglobin values during support were 11.0, 7.7, 6.6, and 3.4 mg/dl, respectively. Under normal conditions, the average daily flow rate ranged from 5 to 6 l/min. During treadmill exercise (10% grade, 1.5 km/h) lasting 20 minutes, peak flow rates exceeded 8 l/min. These pilot studies suggest that this intraventricular axial flow pump is relatively easy to implant, operate, and control. In addition, it is hemocompatible, provides physiologic flow rates, and may be able to provide long-term circulatory support.
We are studying in vivo an intraventricular axial flow blood pump (Jarvik 2000) designed for long-term left ventricular support. The small (25 cc, 85 g) valveless pump has been placed intraventricularly in seven calves; pumps have functioned for as long as 5 months. In the four most recent long-term studies completed, calves have survived for 70, 120, 155, and 162 days (in that order); weight gain has averaged 0.56 kg/day. One study is ongoing at more than 30 days. Under resting physiologic conditions in the normal calf, the continuous flow pump produces flows of 5-6 L/min with a decreased arterial pulse contour. The device has caused no physiologic complications. Calves in the completed studies had mean free plasma hemoglobin levels of 11.4, 7.1, 6.5, and 4.3 mg/dl, respectively. We have modified the inflow structures of the device, and these results suggest that a thrombus free design with no pannus at or around the inlet of the pump can be achieved. Histopathologic analyses of the heart and kidneys in studies of as long as 5 months show no deleterious effects of this device. These studies demonstrate the feasibility of a small implanted intraventricular blood pump for long-term use. Future developments for permanent implantation will include implanted physiologic control systems, transcutaneous energy transmission systems, and implanted batteries.
In this commentary, the question is raised whether prevention research can benefit from resilience research in designing interventions. Although many areas in the investigative interests of prevention and resilience researchers overlap, Luthar, Cicchetti, and Becker may have set the bar too high for defining resilience in the context of varying levels of adversity.
This investigation considers the association between patterns of emotional reactivity and reliance on mother in infancy and cognitive and language developments at age 2. Low-income women (N = 518) and their firstborn infants participated in (1) a lab-based assessment where emotion challenges were presented when the infants were 6 to 9 months old, and (2) an assessment of language and cognitive skills at age 2. After controlling for birthweight, early sensorimotor delay, and age at testing, infants who displayed a pattern of combined high reactivity and high reliance on mother in response to positive, anger, and fear emotion challenges had higher cognitive and language skills at age 2 compared with infants who displayed patterns of low reactivity and low reliance on mother. Children who showed high fearful distress and low reliance on mother and whose mothers had low psychological resources had especially poor developmental outcomes. The role of maternal availability in the socialization of emotion and early communication is discussed.