Biomedical subjects
Publications and source records attributed to M Oppenheimer.
To halt the dramatic alteration in our climate, there must be a reduction in the emission of greenhouse gases. As Bonnie and colleagues discuss in their Perspective, conservation of forests will increase carbon sequestration and decrease greenhouse gas emissions. In this issue, a cost-benefit analysis by Kremen et al. demonstrates the benefits of forest conservation on a local and global scale.
Single-strain regression analysis (SRA) was employed to calibrate the disk diffusion antibiotic susceptibility test for fusidic acid and Clostridium difficile. MIC determinations of 40 clinical isolates of C. difficile were performed with the E-test. The disk diffusion test was standardized according to the Swedish Reference Group for Antibiotics (SRGA). Disks used for SRA contained 1.5, 5, 15, 50 and 150 microg fusidic acid and the routine disk contained 50 microg fusidic acid. A control strain, ATCC 9689, was also tested. SRA constants A and B of the regression lines were calculated. This permitted the determination of zone breakpoints for C. difficile. When applying the pharmacological MIC S and R limits set by SRGA to the E-test results I strain of C. difficile was interpreted as resistant. Zone breakpoints corresponding to the pharmacological MIC limits and calculated using the mean SRA constants for the 40 clinical isolates lead to all strains being interpreted as susceptible. SRA calculations enable laboratories to set up calibrated disk tests with species-related and laboratory-specific interpretations.
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Non-steady state timescales are complicated and their application to specific geophysical systems requires a common theoretical foundation. We first extend reservoir theory by quantifying the difference between turnover time and transit time (or residence time) for time-dependent systems under any mixing conditions. We explicitly demonstrate the errors which result from assuming these timescales are equal, which is only true at steady state. We also derive a new response function which allows the calculation of age distributions and timescales for well-mixed reservoirs away from steady state, and differentiate between timescales based on gross and net fluxes. These theoretical results are particularly important to tracer-calibrated "box models" currently used to study the carbon cycle, which usually approximate reservoirs as well-mixed. We then apply the results to the important case of anthropogenic CO2 in the atmosphere, since timescales describing its behavior are commonly used but ambiguously defined. All relevant timescales, including lifetime, transit time, and adjustment time, are precisely defined and calculated from data and models. Apparent discrepancies between the current, empirically determined turnover time of 30-60 years and longer model-derived estimates of expected lifetime and adjustment time are explained within this theoretical framework. We also discuss the results in light of policy issues related to global warming, in particular since any comparisons of the "lifetimes" of different greenhouse gases (CO2, CH4, N2O, CFC's etc.) must use a consistent definition to be meaningful.
We herein illustrate an unusual but very helpful maneuver in the localization of parathyroid adenomas that have proven difficult to find at initial surgical exploration. This case also illustrates how metabolically active thyroid tumors can interfere with the localization of parathyroid tumors when using the technetium-thallium subtraction scan technique, and a possible way of overcoming such interference.
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While the mammalian chorda tympani innervates taste buds on the anterior two-thirds of the tongue, the chorda tympani of chickens does not enter the tongue, but rather is reported to supply the oral epithelium of the lower beak subjacent to the tongue. This study in the chicken investigated whether the integrity of taste buds in the lower beak is normally dependent upon innervation by the chorda tympani. Following unilateral ligation and removal of a large section of the chorda tympani, animals were sacrificed at 11, 14, and 21 days postoperatively. Oral tissue between the lingual frenulum and beak tip was serially examined, and the presence of each bud was recorded, noting the point at which the bud opened into the oral cavity. No buds were observed on the operated side in any of the cases, while the average bud count on the unoperated side was 33 +/- 10 (SD). On the unoperated side, taste buds were generally associated with anterior mandibular salivary gland ducts that reached surface epithelium and opened into the oral cavity. On the operated side, the cellular organization adjacent to gland ducts and in duct-free epithelium appeared as in control (i.e., bud-free) epithelium. The number of salivary gland duct openings into the oral cavity was equivalent on the operated and control sides. It is concluded that the chorda tympani of chickens innervates taste buds in the anterior lower beak epithelium and that it functions to maintain the structural integrity of these buds.
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Twelve patients with non-Hodgkin's lymphomas of poor prognosis were treated by TACC high-dose chemotherapy (cyclophosphamide 45 mg/kg/day X 4, cytosine arabinoside 200 mg/m2 i.v. q 12 hr X 7,6-thioguanin 100 mg/m2 p.o. X 7 and CCNU 200 or 250 mg/m2 p.o., single dose) followed by autologous bone marrow transplantation (ABMI) (infused dose: 853-20,000 CFU-c/kg). Patients were divided into 2 groups: those in primary therapy with high tumor load (group 1; 3 initial diagnoses, 3 relapses) and those in consolidation therapy for a low tumor load (group 2; 5 complete and 1 partial remissions). Results show that: (1) the aplasia following autologous bone marrow transplantation was short. Leukocyte (greater than 10(9)/1) and platelet (greater than 50 X 10(9)/1) recoveries were observed on day 12 (range, 9-19) and day 14 (range, 8-27). (2) In group 1 there were 3 complete remissions (8,21, 45+ months) and 3 failures, including 1 death to toxicity of TACC. The 3 remissions occurred in patients in primary therapy and overall survival of these patients from the time of initial diagnosis was 48+, 48+ and 60+ months. In group 2 there were 5 persisting complete remissions (12+ to 40+ months) and 1 failure. Overall survival of these patients was 23+, 24+, 27+, 42+ and 70+ months. In both groups failures were associated with contamination of the frozen marrow by tumor. The toxicity of the association TACC + ABMT was acceptable and dominated by the risk of pericardial effusion and infection. The latter was absent in group 2 and occurred in 5/6 cases in group 1. These preliminary results indicate that autologous bone marrow transplantation has a possible role in the aggressive treatment of non-Hodgkin's lymphomas of high-grade malignancy and that its use should preferentially be in the consolidation mode.
Twelve patients with non-Hodgkin malignant lymphoma of poor prognosis were treated with heavy chemotherapy of the TACC type (cyclophosphamide 45 mg/kg/day i.v. X 4; cytosine arabinoside 200 mg/m2/12 hours i.v. X 7; 6-thioguanidine 100 mg/m2/12-hourly p.o X 7 and CCNU 200 or 250 mg/m2 p.o. single dose) followed by autologus bone marrow transplantation (853 to 20.000 CFUc/kg). The patients were divided into 2 groups depending on whether they received an induction treatment for large visible tumoral mass (group I: 3 initial presentations, 3 relapses) or a consolidation treatment for small residual tumour (group II: 6 complete and 1 partial remissions). The results show that autologous bone marrow transplantation shortens the duration of the therapeutic aplasia. White cell (greater than 10(9)/l) and platelet (greater than 50.10(9)/l) recovery was observed on days 12 (range 9-19) and 14 (range 8-27) respectively. In group I, 1 patient died of myocardial TACC toxity and acute renal failure on tumoral kidney; there were 2 failures and 3 complete remissions (8, 21, 45 + months). Remissions occurred in patients treated initially; the overall survival since diagnosis was 48+, 48+ and 60+ months. In group II patients there were 1 failure and 5 complete remissions persisting after a 2+ months to 30+ months follow-up; the overall survival was 23+, 24+, 27+, 42+ and 70+ months. The 3 failures in the series occurred in circumstances suggesting contamination of the cryopreserved bone marrow by tumoral cells. The toxicity, largely due to infection, of the TACC-bone marrow transplantation combination was tolerable. It was clearly lower in group II (6 patients, no septicaemia) than in group I (5/6 patients with septicaemia). These preliminary results confirm that there is room for autologous bone marrow transplantation in highly malignant non-Hodgkin lymphomas, particularly during complete remissions to facilitate the use of an aggressive consolidation chemotherapy.
Thirty-five patients were treated by intensive chemotherapy and/or whole-body irradiation followed by reinjection of cryopreserved autologous bone marrow. In 8 patients the kinetics of recovery of haemopoiesis was delayed (recovery to 10(9) leucocytes/litre beyond day 27 and recovery to 50 X 10(9) platelets/litre beyond day 25). This delay was directly responsible for the death of 3 patients and contributed to a fatal outcome in 2 others (mortality rate 9-14%). Retrospective analysis of these 8 cases revealed that failure of autologous transplantation was associated with poor recovery of CFUc, which was in turn related to an excessively rapid freezing rate after the release of fusion heat. Recovery of CFUc to 50% or more was achieved in 100% of cases when the freezing rate was less than 5 degrees C/min, 45% for freezing rates between 5 and 10 degrees C/min and 22% when the freezing rate exceeded 10 degrees C/min (n = 71, P less than 0.001). There was an inverse linear or logarithmic relationship between CFUc recovery and freezing rate after the transition phase (r = -0.46, r = -0.43, P less than 0.001). The quantity of nitrogen introduced into the freezing chamber to annul the fusion heat must therefore be calibrated with accuracy so that the desired shortening of the transition phase will not be accompanied by an overly marked increase in the freezing rate, which would result in the destruction of stem cells. To ensure an adequate freezing rate, it is crucial to monitor the temperature continuously in each sample of bone marrow during the freezing process. This study also suggested that other factors may have interfered with the kinetics of recovery after autologous bone-marrow transplantation. These factors include myelofibrosis, the presence of an Australia antigen and administration of compounds that are toxic for the bone marrow after reinjection of cryopreserved marrow. However, the responsibility of these factors cannot be stated with certainty.
Two female patients with grade IV primary biliary cirrhosis, untractable pruritus, arthralgias and xanthomatous neuropathy in one case, underwent long term plasmapheresis for 30 months (on a continuous centrifugation cell separator) and 18 months (on capillary plasma filters). Plasma exchange were performed monthly and substitution achieved by diluted human serum albumin. No major side effect occurred. Pruritus, arthralgias and xanthomatous neuropathy greatly improved or even disappeared. The plasma levels of transaminases, albumin, globulin and clotting factors were stable, alkaline phosphatases slightly diminished. Bilirubin, after an initial fall at 6 months, increased again. Cholesterol stabilized at near normal values. Bile acids blood levels decreased in both cases.
Two experiments were conducted in an attempt to replicate the findings of Touchette's classic 1971 experiment. The results obtained were more variable than those obtained by Touchette. Four of 34 subjects learned the Horizontal E discrimination without errors. Ten subjects preempted the red prompt stimulus erroneously. Twelve subjects failed to preempt. Among those who failed to preempt, at least six had not learned the target discrimination. There were also five subjects who failed to preempt who, on subsequent tests, demonstrated that they had learned the target discrimination. For these subjects, the onset of the prompt appeared to grant "permission to respond." An attempt is made to account for the differences in the current results and those of Touchette (1971). We also compare our results to the usually successful application of the delayed prompt to education and training problems. We note that the procedures used in these successful applications are often quite different from those in the original Touchette experiment and our own.
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