Biomedical subjects
K Newman
Publications and source records attributed to K Newman.
A high-precision automatic closed-circuit respirometer for small animals.
An automatic apparatus for the continuous measurement of O2 consumption of small laboratory animals is described. By use of a high-sensitivity pressure transducer with associated circuitry together with a peristaltic O2 delivery system, the closed respirometer chamber is maintained at atmospheric pressure +/- 0.5 mmH2O. O2 delivery is measured to within 0.25 ml by recording rotations of the peristaltic pump, following calibration by the withdrawal of a preset volume of air from the chamber. Static trials (with the chamber empty) indicate a high degree of reproducibility of data with the chamber pressure remaining at atmospheric pressure +/- 0.5 mmH2O as a result of the proportional, as opposed to fixed-volume, delivery of O2. Trials with mice and rats have likewise produced data with a high degree of reproducibility.
T-cell-independent elimination of Borrelia turicatae.
Mice deficient or deprived of thymus-derived lymphocytes eliminated blood-borne Borrelia turicatae with efficiency comparable to that observed in normal littermates. When challenged with 10(5) borreliae, nude mice had mean (+/- standard deviation) primary spirochetemias lasting 3.1 +/- 0.2 days and mean (+/- standard deviation) peak bacterial counts of 3.0 X 10(7) +/- 0.5 X 10(7) cells per ml of blood; in comparison, heterozygous littermates and normal mice had respective primary spirochetemias lasting 3.4 +/- 0.6 and 3.2 +/- 0.2 days and respective peak counts of 8.0 X 10(7) +/- 1.5 X 10(7) and 5.5 X 10(7) +/- 0.9 X 10(7) bacterial cells per ml of blood. No increased responsiveness to concanavalin A was observed in infected nude mice, indicating the sustained lack of maturate T cells in these animals. Thymectomized and steroid-treated mice were also found to eliminate circulating borreliae with efficiency comparable to that observed in control animals. Irradiation of mice abrogated responsiveness to borreliae, but reconstitution with T-cell-depleted splenocytes restored antibody production. It is proposed that elimination of B. turicatae is mediated by a T-cell-independent immune response mechanism.
Fertility regulation in the 21st century.
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In vivo evidence that an intact lytic complement pathway is not essential for successful removal of circulating Borrelia turicatae from mouse blood.
Complement component C5-deficient mice were found to be able to eliminate blood-borne Borrelia turicatae as effectively as normocomplementemic control animals. The absence of C5 and the resultant loss of hemolytic complement activity were confirmed for the deficient mouse strains used. Immunofluorescent staining of complement component C3 on blood-derived borreliae could be readily accomplished as early as 2 days before spirochetal elimination from all mice tested. These observations would suggest that C3 deposition was occurring, even though the terminal lytic steps were blocked in the complement-deficient mice. We propose that spirochetolysis is not requisite for successful removal of borreliae from the circulation of mice.
Amitriptyline in human breast milk and the nursing infant's serum.
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Effects of castration and chronic morphine administration on liver alcohol dehydrogenase and the metabolism of ethanol in the male Sprague-Dawley rat.
The effects of castration on liver alcohol dehydrogenase (ADH) activity and the in vivo metabolism of ethanol were examined in the male Sprague-Dawley-derived rat. It was found that castration led to immediate (24 hr) increases in the ADH-dependent metabolism of ethanol which persisted for at least 6 weeks postcastration. Testosterone completely reversed the effects of castration. Moreover, when increases in liver ADH activity and the metabolism of ethanol were allowed to develop to maximal levels (2 weeks), a single s.c. injection of testosterone promptly reversed the effects of castration, such that by 24 hr castrated animals were indistinguishable from controls. Thus, it appears that in the male Sprague-Dawley-derived rat liver ADH activity and the in vivo metabolism of ethanol are under the control of testosterone. Because narcotics have also been shown to depress serum testosterone levels, and there is good evidence of significant pharmacological and biochemical interactions between the narcotics and ethanol, we examined whether chronic administration of morphine led to testosterone-reversible increases in the ADH-dependent metabolic disposition of ethanol. We found that chronic morphine administration, at doses sufficient to markedly depress serum testosterone levels (> 85%), produced large increases in liver ADH activity and the clearance of ethanol. Concurrent administration of testosterone completely abolished this effect. These data may, therefore, provide the first evidence of a biochemical mechanism involved in the interactions between morphine and ethanol. Furthermore, our results suggest that drug-induced reductions in serum testosterone may serve as an important mechanism involved in the cross-tolerance observed between ethanol and many abused, sedative-hypnotic drugs which share the common ability to decrease serum testosterone.
Moxalactam and piperacillin: a study of in vitro characteristics and pharmacokinetics in cancer patients.
We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients. The regimens consisted of moxalactam (4 g.i.v. q12h) plus piperacillin (75 mg/kg i.v. q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6-8 mg/l). Detailed pharmacokinetics were ascertained for the beta lactams. All drugs were active against a panel of 11 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval. Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results against S. aureus and P. aeruginosa. In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen. This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried by P. aeruginosa (among others). Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.
Psychogenic seizures in old age: a case report.
Psychogenic seizures are unusual after age 60 years. A 73-year-old woman had onset of psychogenic seizures at age 69 years. Five to six attacks occurred each month, usually at night, characterized by an initial subjective sensation and headache followed by generalized stiffening and shaking. Continuous EEG-closed circuit television (EEG-CCTV) monitoring clearly showed these episodes to be nonepileptic. Discontinuation of antiepileptic drugs (AEDs) did not increase the frequency or severity of attacks. Epileptiform discharges were not recorded during the awake, drowsy, or sleeping states. Psychiatric evaluation identified significant turmoil in the patient's life and a history of childhood sexual and physical abuse. Psychogenic seizures may begin in old age and should be considered in the differential diagnosis of intractable seizures in the elderly. Predominantly nocturnal occurrence should not exclude the diagnosis.
Global aphasia with seizure onset in the dominant basal temporal region.
A 33-year-old right-handed woman had intractable simple and complex partial seizures (SPS, CPS) that began with global aphasia. EEG closed-circuit TV (EEG-CCTV) monitoring with sphenoidal electrodes showed left inferomesial temporal ictal onset of CPS. Subdural electrodes were implanted over the left frontotemporal convexity, subtemporally and subfrontally. Stimulation of the basotemporal cortex produced global aphasia. A posterolaterotemporal language area was also identified. Spontaneous SPS had focal onset in the basal temporal language area (BTLA). Ictal discharges did not involve the posterotemporal region. This case shows that aphasic speech arrest at seizure onset may be due to seizure discharge in the basotemporal region and that the BTLA is clinically relevant in seizure semiology.
Fit for nursing at St Andrew's.
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