Survival after high blood alcohol levels. Association with first-order elimination kinetics.

A patient survived acute alcohol intoxication with an unprecedented blood alcohol level of 1,500 mg/dL. Treatment included peritoneal dialysis and intravenously administered fructose. Alcohol elimination followed first-order kinetics, in which the elimination rate is proportional to concentration, rather than zero order in which the metabolic rate is independent of concentration. The report provides further evidence for first-order elimination kinetics with high blood alcohol levels and for an adaptive increase in alcohol metabolism with long-term alcohol consumption.

EEG recognition of Aicardi's syndrome.

Thirty-two EEGs from six cases of Aicardi's syndrome were reviewed. A characteristic EEG pattern was found in all cases. This consists of multifocal epileptiform abnormalities occurring on a burst-suppression pattern showing complete asynchrony between the two hemispheres. This pattern has been described so far only in Aicardi's syndrome. These characteristic EEG features are more readily found early in the course of the disease and occur less frequently six months after from the onset of symptoms, at which time they are often replaced by multiple epileptic foci on a severely disorganized background. The EEG sleep pattern was profoundly altered in all stages of the disease. The EEG is considered a helpful tool in the diagnosis of Aicardi's syndrome.

Within-breath measurement of respiratory impedance.

The measurement of the complex respiratory impedance at a high temporal resolution is described. The measurement of impedance is correlated with the breathing cycle using electrical transthoracic impedance. This allows the determination of the complex impedance at any fixed point in the respiratory cycle, which results in lower variability in the measured data when compared to the original device. The respiratory impedance in normal subjects fluctuates during the breathing cycle and has two maxima during a single breath, which occur at peak inspiratory and expiratory flow. In addition, the measurement of impedance at a high temporal resolution enables the observation of novel features in the impedance which appear to be associated with certain respiratory disorders.

Lung pathology in HIV positive patients.

We describe the results of 43 bronchoscopic examinations carried out on 35 patients who were HIV positive. Of these, 13 were intravenous drug abusers, 13 were homosexual or bisexual, six were haemophiliacs, two were homosexual intravenous drug abusers and one was a heterosexual contact of a drug abuser. All underwent investigation because of respiratory symptoms. Aetiological diagnosis could not be made from physical examination, x-ray or routine laboratory tests but, was usually made using bronchoscopy and its associated investigations. Using these techniques, Pneumocystis carinii pneumonia was the commonest diagnosis (19 cases) followed by bacterial infection. Mycobacterial infection accounted for two cases and non-specific interstitial pneumonitis accounted for three. Kaposi's sarcoma was found in one instance and eight investigations were non-diagnostic.

A clinico-pathological study of 79 bronchoscopies in HIV-positive patients.

We investigated lung pathology in 61 HIV-positive patients who underwent 79 bronchoscopies. There were 27 cases of pneumocystis carinii pneumonia (PCP), 22 cases of pyogenic pulmonary infection and six cases of mycobacterial infection. Eleven cases of non-specific interstitial pneumonitis were found and 10 intravenous drug abusers had birefringent pulmonary talc granulomata in biopsy specimens. Women and intravenous drug abusers had higher rates of pyogenic pulmonary infection than men and other risk groups respectively. When compared with a previous survey from the same hospital using the same methodology the present study showed a change in the risk groups with 50% more intravenous drug abusers, 42% more haemophiliacs and 45% fewer patients with sexually transmitted infection. However, apparent changes in the spectrum of diseases encountered were not significant.

Relationships between disaccharide hydrolysis and sugar transport in amphibian small intestine.

1. A study is described of the relationships which exist between disaccharide hydrolysis and glucose transport in the small intestine of Rana pipiens and Bufo vulgaris. The experiments were undertaken on the intestine perfused in vitro through the vascular system and with fluid circulating through the intestinal lumen. For this system it was found that, with [U-(14)C]glucose in the intestinal lumen, the apparent specific activity of the glucose appearing in the vascular effluent was not significantly different from that in the lumen.2. Changes of ionic composition of vascular and luminal fluids, and the presence of phloridzin or strophanthin, had little effect upon the maltase activity in situ in R. pipiens, although this activity was somewhat reduced when the sodium of the intestinal lumen was replaced by lithium. In contrast, in all cases a marked reduction was found in the rate of glucose translocation in the vascular effluent.3. With Tris substituted for the luminal sodium, there was evidence of a competitive inhibition of the maltase activity in situ by the buffer cation. At the same time, the rate of glucose translocation into the vascular effluent was but little affected and there was an apparent increase in the efficiency with which the cellular systems responsible for the translocation were able to capture the glucose liberated.4. It was found that competition for transepithelial translocation occurred between the glucose initially present in the intestinal lumen, and glucose derived from either maltose or trehalose. There was no evidence for competition for hydrolysis between maltose and trehalose, yet the glucose units derived from these two disaccharides competed with each other for translocation.5. The significance is discussed of the finding that it is possible to dissociate the processes of disaccharide hydrolysis from those underlying the translocation of hexose units into the vascular effluent. It is suggested that monosaccharide units released by the hydrolysis of disaccharide molecules have access to a pool of glucose which is equally accessible to glucose free in the intestinal lumen. It is also suggested that the rate of transport of glucose from the pool into the vascular effluent (i.e. glucose translocation) is determined by the concentration of glucose within the pool. From consideration of the properties of a model operating upon these principles, it is possible to predict the relative contribution of disaccharides and monosaccharides in the intestinal lumen to the glucose appearing in the vascular effluent. The experimentally determined contributions of the two sources are very similar to those predicted from the model. The implications of possible sites for the postulated pool are discussed.

Disaccharide absorption by amphibian small intestine in vitro.

1. An account is given of the absorption of disaccharides by the small intestine of Rana temporaria, R. pipiens and Bufo vulgaris perfused in vitro through the vascular system. Maltase and trehalase activity are found in the intestine of all three species; very small amounts of sucrase are present in the intestine of R. pipiens but there is no evidence for the presence of lactase in any of the animals studied.2. During maltose absorption free glucose appears in the vascular effluent and in the intestinal lumen. Only very small quantities of disaccharide are found in the vascular effluent. The concentration of free glucose in the intestinal lumen during maltose absorption is not high enough to account for the rates of glucose transport observed. The rate of appearance of glucose in the vascular effluent is determined by the concentration of disaccharide in the luminal fluid, and hexose, free in solution in the lumen, is not an obligatory intermediate in the process of disaccharide absorption.3. For R. pipiens more than 90% of the maltase activity in the system is present in the intestinal wall and the rate of maltose hydrolysis by maltase, free in the intestinal lumen, is found to be inadequate to account for the rates of appearance of glucose observed to occur in the lumen and in the vascular effluent. It is not possible to wash away maltase activity from the intestinal wall.4. The kinetic properties of maltase and trehalase acting in situ are of the Michaelis-Menten type; the apparent K(m) is 2 mM for maltase, and 3 mM for trehalase.5. The relationship which exists between the rate of absorption of glucose and the concentration in the luminal fluid of either disaccharide or free glucose is of the Michaelis-Menten type. Expressed in molar units, the apparent K(m) for the glucose transport is about one fifth that of the disaccharidase. The maximum rate of glucose transport observed is less than the maximum rate of disaccharide hydrolysis. In R. pipiens equimolar concentrations in the intestinal lumen of the monomer free glucose, or of the dimer, maltose, yield approximately equal rates of transport of the free hexose.6. It is concluded that in the amphibian, either intestine disaccharide hydrolysis and glucose transport are functions of separate subcellular systems which spatially are very closely related, or that the hydrolysis and transport are different facets of the activity of a common system.

A preparation of perfused small intestine for the study of absorption in amphibia.

1. A preparation of amphibian small intestine perfused through its vascular system is described. Vascular perfusion with a bicarbonate Ringer solution containing a colloid is used to control the composition of the environment of the submucosal faces of the absorbing cells and to carry away for collection any material extruded from these cells. Oxygenation of the mucosal cells is derived primarily from fluid circulated through the intestinal lumen. The preparation exhibits physiological properties of transport for periods of up to 5 hr. After 5 hr perfusion the epithelial cells show no signs of gross cellular damage when examined either by light or by electron microscopy.2. The relationship between the hydrostatic pressure at the mesenteric artery and the rate of perfusion through the vascular bed is substantially linear. The pressure-flow relationships in the mesenteric bed, including an apparent ;critical closing pressure', are primarily determined by the hydrostatic pressure in the intestinal lumen. Alterations in the hydrostatic pressure in the intestinal lumen also change the relative proportions of the vascular infusate which appear in the portal venous effluent and in the fluid exuded from the serosal surface of the preparation (;sweat'). Hydrostatic distension pressures above about 10 cm H(2)O reduce the rate of collection of fluid from the portal vein and increase the rate of collection of ;sweat'.3. An increase in the rate of vascular perfusion increases the total rate of glucose appearance although the glucose concentrations in both the portal effluent and the ;sweat' are reduced.4. The glucose translocation rate is related in an alinear saturable fashion to the luminal concentration of glucose. By making a correction for metabolic loss of glucose during its passage through the intestinal cell, the relationship existing between the lumen concentration and the uptake of the sugar by the mucosal cells has been calculated. This relationship is found to fit Michaelis-Menten type kinetics. The K(m) of the intestinal translocation process for glucose in Rana pipiens was 0.45 +/- 0.13 (4) muM. The mean V(max) was 137.5 +/- 35.3 (4) muM/hr/g fat-free dry wt.5. When phlorrhizin (10(-5)M) is added to the vascular perfusate, no inhibition of glucose transport is seen for at least 60 min. When strophanthin is added to the vascular perfusate (5 x 10(-5)M), a markedly greater inhibition of glucose transport is observed than when it is introduced to the luminal circulation.6. Earlier studies of the vascular perfusion of isolated small intestine are tabulated. The experimental findings are discussed in relation to a model of the mode of action of the epithelial cell for glucose transport.