Antiviral treatment in chronic infection with hepatitis B virus.
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Biomedical subjects
Publications and source records attributed to G Alexander.
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Fifteen sheep fetuses hypophysectomized around 115 days gestation (term 150 days) were treated with growth hormone (GH), adrenocorticotrophin (ACTH) or triiodothyronine (T3) by continuous intravenous infusion. At normal or caesarian delivery, about 149 days gestation, body weights and dissectible internal brown fat and subcutaneous white fat depots were compared with seven control hypophysectomized fetuses and four sham-operated controls, the latter groups receiving no hormone infusions. Hypophysectomy caused the appearance of a large persistent depot of subcutaneous fat which was unaffected by ACTH or T3 infusion. Treatment with ovine pituitary GH resulted in the disappearance of this depot which was also absent from the sham-operated controls. Although the GH source was not subjected to extensive purification, there was very little contamination with prolactin or TSH, suggesting that GH itself has a major role in the control of lipid metabolism in the fetus.
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A case of hemobilia due to a hepatic artery aneurysm is described. Despite 2 arteriograms and 2 laparotomies, the cause of the bleeding remained undetected until a further selective cannulation of the celiac axis artery was performed. Endoscopic retrograde cholangiography demonstrated that postoperative jaundice was not due to obstruction and outlined the aneurysm within a hepatic duct.
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Serum gentamicin levels were measured by agar diffusion bioassay in 38 patients undergoing treatment with clindamycin-gentamicin for post-cesarean endomyometritis. Patients received intravenous gentamicin in a dose of 1 mg/kg actual body weight every eight hours. All trough levels were less than 1 microgram/ml. The mean 30-minute postinfusion level was 5.78 +/- 2.43 micrograms/ml (mean +/- SD). The range of postinfusion concentrations was 1 to 12 micrograms/ml. Postinfusion concentrations were less than 5 micrograms/ml in 13 patients, but none of these individuals experienced a clinical failure of antimicrobial therapy. There were no statistically significant differences in mean age, weight, hematocrit, serum creatinine, estimated creatinine clearance, or administered dose in patients with therapeutic gentamicin levels and patients with apparent subtherapeutic levels. The authors conclude that postinfusion gentamicin concentrations fluctuate widely in obstetric patients receiving 1 mg/kg/dose and that apparent subtherapeutic postinfusion levels still may be clinically efficacious, depending upon the antimicrobial susceptibility of the infecting microorganisms.
Keratoacanthoma (KA) is a relatively common skin lesion of questionable histogenic origin. Although cutaneous KAs are considered to arise from hair follicles, the rare cases reported occurring on mucous membranes would suggest possible origin from surface epithelium. A review of the literature revealed six previous cases involving oral mucosa. Seven new cases of keratoacanthoma are presented. Four occurred on the lower lip, and three arose from intraoral mucosal tissue, accounting for a total of nine reported intraoral cases.
Stable and radioactive isotopes of an element have been utilized to study a variety of complex phenomena including metabolic pathways and enzyme reactions. It is generally assumed that isotopes of an element are not treated in a differential manner. Nevertheless we have demonstrated that the two stable isotopes of lithium (Li), one of mass 6 and the other with a mass of 7, are differentially taken up by red blood cells with 6-8% higher quantities of 6-lithium (6Li) being accumulated. We report here on the in vivo pharmacokinetics of Li isotopes. Nineteen adult cats were given a single dose of either 6LiCl by gastric intubation (1 meq/kg) and 2 weeks later the treatment was crossed. Plasma concentrations of the two Li isotopes were determined. In another series of studies 19 adult cats were given either 6LiCl or 7LiCl by intubation, cerebrospinal fluid (CSF) and blood samples were collected simultaneously and isotropic Li concentrations of the spinal fluid and plasma were determined. The average plasma concentration of 6Li was higher than 7-lithium (7Li) between 2 and 9 hr postadministration. The elimination curve for both isotopes had an initial fast and later slow component. For the slow component 6Li had an average half-life of 12.9 and 7Li 15.9 hr. Comparison of the CSF/plasma ratio for 6Li and for 7Li indicated that the ratios were higher for 6Li than 7Li 2-6 hr after administration. These data suggest that factors in addition to concentration gradients influence the transport of Li isotopes across the blood-brain barrier. These studies demonstrate the acute pharmacokinetics of the two Li isotopes are not the same in compartmental distribution and rate of disappearance from plasma. It is conceivable 6Li may have a greater toxic or therapeutic effect than 7Li in the treatment of manic-depressive illness.
Adrenalectomy and various replacement regimens with corticosteroids and catecholamines were used to assess the role of the adrenal secretions in cold thermogenesis in young lambs. A dose of cortisol of 0.25 mg kg-1 d-1 was sufficient to increase summit metabolism significantly in lambs that had been adrenalectomized for at least 1 week, but even the massive dose of 16 mg kg-1 d-1 restored the response to only 85--90% of that in intact lambs. However, the remaining 10-15% deficit was largely restored by additional infusion of catecholamines, principally adrenaline, and there was no significant interaction between the responses to cortisol dose and to catecholamine infusion. Heart rate, arterial blood pressure and cardiac output during summit metabolism all increased with increasing dose of cortisol. Hyperglycaemic responses to cold exposure were low in adrenalectomized lambs receiving less than 0.25 mg kg-1 d-1 of cortisol, and the normal hyperlactacidaemia in intact lambs during summit metabolism was apparent only in lambs receiving more than 1 mg kg-1 d-1, unless adrenaline was also given. The increase in summit metabolism due to adrenaline was accompanied by increased shivering. There was no effect on heart rate and blood pressure, but adrenaline increased cardiac output through an apparent increase in cardiac stroke volume and a decrease in total peripheral resistance. Strong correlations of the increase in summit metabolism with the increase in cardiac output and with adrenaline-mediated increases in plasma glucose and lactate, indicate that a role of the medullary catecholamines is to maintain maximal thermogenesis by their effects on the supplies of oxygen and energy substrates to the thermogenic tissues.
Thirty patients at term undergoing cesarean section received intraoperative irrigation with either cefamandole, cephalothin, or ampicillin to prevent postoperative infection. Serum drug levels were measured at 15, 60 and 120 minutes after completion of irrigation. Serum levels at each sampling interval were highest for cefamandole and lowest for cephalothin. Les than 2% of the total drug dose was excreted in the urine during the first 2 postoperative hours. In most patients, maximum serum antibiotic concentrations exceeded minimal inhibitory concentrations for several recognized pelvic pathogens. It is concluded that the mechanism of action of intraoperative irrigation may in part be due to systemic absorption of antibiotic and not simply to a local effect on the endometrium. Moreover, the degree of systemic absorption may be sufficient to cause allergic drug reactions and to exert selective pressures for the emergence of drug-resistant microorganisms.
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Studies to investigate the relative value of sight, hearing and smell in mutual recognition between ewes and lambs are described. The method used was to alter clues that could aid in recognition, rather than interfering with the animal's sensory perception. When lambs were coloured with powdered dyes to change appearance, this produced marked avoidance by the dams of the treated lambs. When lambs were partially coloured, the ewes' greatest reaction was shown to lambs whose heads were coloured. Other experiments compared the role of vision and hearing by observing recognition when the ewes or lambs were hidden behind screening, or muted. The results indicate that while olfaction is important for recognition when the ewe and lamb are close together, visual clues are of major importance in maternal discrimination and auditory clues are important for the lambs as they get older.
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Fetal sheep were injected intramuscularly with 25-100 mg/kg of 6-hydroxydopamine HBr on 3-4 occasions between the 94th and 136th day of pregnancy. Following birth, which took place normally, the metabolic response to cold (summit metabolism) was found to be lower in treated than in control lambs, by an amount that approximated the thermogenic potential of brown fat. Under thermo-neutral conditions, the dose of infused noradrenaline (10 microgram kg-1 min-1) that stimulates maximum non-shivering thermogenesis in control lambs failed to stimulate thermogenesis in treated lambs unless accompanied by a dose of the alpha-blocker, phentolamine. This failure was apparently due to vasoconstriction induced by hypersensitivity to noradrenaline; hypersensitivity was also indicated when one-tenth of this dose was found to be fully effective in stimulating metabolism and substrate mobilization of the treated lambs. Examination of the perirenal adipose tissue of treated lambs with the electron microscope and by a monoamine fluorescence technique that visualizes catecholamine-containing structures, revealed that the tissue possessed the histological characteristics of brown fat, but there was little or no evidence of sympathetic innervation, in contrast with profuse innervation in control lambs. This is consistent with the observed hypersensitivity to noradrenaline. Similar histological findings were made in lambs that had received weekly intraperitoneal injections of 6-hydroxydopamine from day 70 of gestation, after which time sympathetic innervation normally begins to appear. It is probable that an intact sympathetic innervation is unnecessary for normal development of brown adipose tissue. This chemical sympathectomy appears to be long-lasting since treated lambs 8-months old were unable to vasoconstrict their extremities effectively in response to cold, and significant monoamine fluorescence could not be demonstrated in the various tissues examined.
Fourteen fetal sheep were treated in utero with a single intramuscular injection or three to four injections of 6-hydroxydopamine. After birth the cardiovascular responses of these lambs to adrenergic drugs were studied and compared with the cardiovascular responses of untreated newborn lambs. Lambs which received three to four injections of 6-hydroxydopamine were more sensitive to the pressor actions of noradrenaline and phenylephrine than were control lambs or lambs which received a single injection of 6-hydroxydopamine. The supersensitivity to noradrenaline persisted in multiple treatment lambs until at least 5 months of age. Lambs which received multiple injections of 6-hydroxydopamine were also subsensitive to the pressor action of tyramine. The sensitivity to the pressor actions of noradrenaline and phenylephrine in lambs which received a single injection of 6-hydroxydopamine lay between that of control and multiple treatment groups. Despite the pharmacological evidence of impairment of sympathetic innervation of peripheral blood vessels plus a lack of responsiveness of these lambs to alpha-adrenergic blockade with phentolamine, treated lambs had arterial pressures and heart rates similar to control lambs. As well, treated lambs showed no impairment in their ability to reflexly regulate heart rate in response to changes in arterial pressure, which is consistent with the recently reported vagal control of the cardiac baroreceptor reflex.