Uptake and biotransformation of sevof lurane in humans: A comparative study of sevof lurane with halothane, enflurane, and isoflurane

Study Objective: To compare the volatile anesthetic sevoflurane with halothane, enfurane, and isof urane on the uptake and biotransformation in humans.

Design: Prospective pharmacokinetic study of sevofurane administration in human subjects.

Setting: Inpatient surgery clinic at a university medical center.

Patients: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia.

Interventions: The patients were assigned randomly to one of four groups: halothane, enflurane, isofurane, or sevofurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enfurane, 1.85%; isofurane, 1.27%; and sevofurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes.

Measurements and Main Results: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevofurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m²/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m²/MAC; degradation rate 15.7%), enfurane (1150 ml/m²/MAC; 1.3%), and isofurane (439 ml/m²/MAC; 0.6%) were also conducted. Sevofurane had a peak serum inorganic fluoride concentration of 19.3 μmol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively.

Conclusions: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC *1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rade was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane.     

Validity of a hinged constant force probe and a similar, immobilised probe in untreated periodontal disease

The validity of a hinged constant force probe (0.25 N) was compared with that of a similar but immobilised instrument, using the same interchangeable tip for both (0.64 mm diameter; 2 mm divisions). 60 sites were measured on teeth which were extracted subsequently, in patients with untreated periodontal disease, and the connective tissue attachment level was used as validity criterion. The clinical measurements of both probes correlated well with each other, but they differed significantly from the post-extraction connective tissue attachment level measurements, indicating a point 1.2 mm coronally to this, on average. A companion investigation of intra-operator probing depth reproducibility with the 2 probes, was undertaken in 14 patients, at 2 visits separated by 1 week in each case. All patients had untreated periodontal disease. A difference between probes was found at the first visit, but not at the second; the immobilised probe showed a difference between visits, reducing mean probing depth slightly at the second; when the immobilised probe was used first, there was a difference between probes. Further analysis of the results indicated that there was greatest agreement between probes when the constant force probe had been used before the immobilised probe at the second visit. The results suggested that these probes indicated a point above the connective tissue attachment level, related to pocket morphology, and that there was a moderate learning effect due to operator use of the constant force probe, which modified use of the immobilised probe.     

Expression of a 10.5 kDa inhibin in the endometrium of bonnet monkey on treatment with an antiprogestin ZK 98.299: An immunocytochemical study

Immunocytochemical localization of inhibin was carried out in paraffin embedded tissue sections of the control and antiprogestin (ZK 98.299)-treated bonnet monkey endometrium using polyclonal antibodies generated against human seminal plasma inhibin (10.5 kDa). The study shows that administration of low doses (5 mg/ week) of antiprogestin results in an increase in the expression of inhibin by the endometrium. Treatment with higher doses (20 mg/week) caused a decrease in the expression. Since treatment with higher doses also caused atropic changes in the endometrium, the decrease in inhibin could be the result of morphological damage to the endometrium rather than the effects of antiprogestin on the expression of inhibin. The potential involvement of endometrial inhibin in the process of nidation is speculated.     

Angiogenesis and the blood-brain barrier in intracerebral solid and cell suspension grafts

Solid and suspension grafts of fetal central nervous system (CNS) tissue rapidly reform an intact blood-brain barrier (BBB), whereas solid grafts of peripheral nervous system (PNS) tissue fail to establish a BBB as detected by horseradish peroxide (HRP) leakage, administrated intravenously. We examined the acute changes in the BBB after grafting of fetal CNS tissue in solid and suspension form and superior cervical ganglion (SCG) and PNS tissue in the same manner. Adult rats (n = 20) received fetal (day 14–15) forebrain grafts (either solid or cell suspension) to their rostral corpus callosum bilaterally. A second group (n = 20) received SCG solid and cell suspension grafts at the same coordinates with the same technique. The animals were killed on first, third, seventh, and tenth days after grafting. Intravenous HRP (Sigma, type VI, 75 mg/5-g rat) was given 1 hour before perfusion with mixed aldehydes. Fifty-micron coronal sections were examined for the presence and location of the graft by cresyl violet and AChE staining and Mesulam's TMB method to detect HRP leakage. HRP leakage was detected in the parenchyma in all groups on the first and the third days post-transplantation indicating a disrupted BBB. No HRP reaction was seen at days 7 and 10 in groups receiving fetal forebrain tissue whether solid or cell suspension. Solid grafts of SCG consistently demonstrated HRP leakage from the first through the tenth day. However, cell suspension of SCG established a BBB by 7 days. These results suggest that within the solid grafts of CNS and PNS tissue, the permeability of the vessels is dictated by the transplanted tissue itself. When cell suspensions of the same tissue are introduced, host CNS tissue dominates as the local environment resulting in non-leaky vasculature within the graft.     

Safety of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III)

In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III.

Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity.     

Malnutrition and subsequent ischemic heart disease in former prisoners of war of world war II and the Korean conflict

The harsh treatment of former prisoners of war (POWs) of World War II and the Korean conflict resulted in severe malnutrition. Although rarely linked to specific long-term medical problems, a specific marker of malnutrition, self-reported lower limb edema (presumably due to a vitamin B deficiency) was associated with a three-fold increase in subsequent death attributed to ischemic heart disease (IHD) during the follow-up period from 1967 through 1975. Although there is at present no medical basis for linking edema, which is perhaps a marker for some unmeasured risk factor, to subsequent IHD, this finding may nonetheless have medical implications for the group of former POWs and other populations with severe dietary deficiency. It also suggests there may be a need to reexamine currently held theories on malnutrition and subsequent chronic disease.     

The effect of milk and casein proteins on the adherence of Streptococcus mutans to saliva-coated hydroxyapatite

Experiments sought to determine the nature of the binding of milk proteins to hydroxyapatite (HA) and to saliva-coated hydroxyapatite (sHA), and to determine the effect of milk and casein on the adherence of Streptococcus mutans GS-5 to sHA. The binding of radiolabelled -casein to HA was reduced when incubated simultaneously with parotid saliva, and enhanced in the presence of milk. The binding of β- and κ-casein to HA was unaffected by the presence of parotid saliva and enhanced by the presence of milk. The in vitro bacterial adherence of Strep. mutans GS-5 to sHA beads was reduced when beads were coated with milk instead of buffer, or when bacteria were added to sHA in the presence of milk instead of buffer. Casein proteins (, β, κ) added to sHA simultaneously with bacteria inhibited the adherence of Strep. mutans GS-5 to sHA. κ-Casein, when bound to sHA, inhibited streptococcal adherence to sHA; - and β-casein, when bound to sHA, had no effect on streptococcal adherence. Fractionation of κ-casein by anion-exchange chromatography revealed the anti-adherence activity of κ-casein was mediated primarily by a 40,000 mol. wt. glycoprotein-containing fraction. These data show that milk, particularly κ-casein fractions, can modulate the adherence of Strep. mutans GS-5 to SHA surfaces in vitro.