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Background To investigate whether “binge” and escalating alcohol exposure in the rat influences the development of pathological liver injury. Methods Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia-inducible factor 1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage. Results In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16-week period. The levels of COX-2, oxidative stress, nitrosative stress, HIF-1, proinflammatory mediators (tumor necrosis factor-α, interleukin 1β [IL-1β], IL-6), and procollagen-I were increased over the 16-week period. The content of IL-10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter and was significantly decreased at 12 and 16 weeks. Conclusions A rat model of alcoholic liver disease (ALD) with long-term binge and escalating ethanol exposure was developed. Our data support the hypothesis that enhanced eicosanoid production by COX, oxidative stress and nitrosative stress, HIF-1, and the imbalance between pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of ALD.

Thromboxane levels are increased in rats fed ethanol (EtOH), whereas thromboxane inhibitors reduce alcoholic liver injury. The aim of this study is to determine whether thromboxane inhibitors could attenuate the already established alcoholic liver injury.Rats were fed EtOH and liquid diet for 6 weeks by intragastric infusion to induce liver injury after which EtOH was continued for 2 more weeks, and the rats were treated with either a thromboxane synthase inhibitor (TXSI) or a thromboxane receptor antagonist (TXRA). Liver pathology, lipid peroxidation, nuclear factor-kappa-B (NF-κB) activity, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and transforming growth factor-beta1 (TGF-β(1) ) were evaluated.Administration of fish oil and EtOH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF-κB activity, and expression of TNF-α, COX-2, and TGF-β(1) . Treatment with the thromboxane inhibitors ameliorated a certain level of the pathological and biochemical abnormalities. In particular, TXSI in addition to reducing necrosis, inflammation and fibrosis also decrease the severity of fatty liver.Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued EtOH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease.

Scope Lycium barbarum polysaccharide (LBP) is a water fraction of wolfberry, which has been demonstrated to possess a hepatoprotective effect in several liver disease models. However, the anti-alcoholic liver disease (anti-ALD) mechanism of LBP has not been investigated thoroughly. Its protective effects on both male and femal mice are investigated in the current study. Methods and results A chronic ethanol-fed ALD in vivo model is applied to study the effect of LBP in both male and female mice. It is observed that ethanol causes more severe liver injury in female than male mice, and the ameliorative effects of LBP are also more significant in female mice, which are impaired after complete bilateral oophorectomy. The hepatic SCD1 expression is found to be positively correlated with the severity of the liver damage and the main mediator of LBP inducer of protection. The AMPK-CPT pathway is also activated by LBP to rebalance the dysregulated lipid metabolism during ALD development. By using concurrent sodium palmitate and an ethanol-induced in vitro cell damage model in AML-12 cell line, it is characterized that LBP directly interacts with ERα instead of ERβ to activate the SCD1-AMPK-CPT pathway. Conclusions LBP is an effective and safe hepatoprotective agent against ALD primarily through the SCD1-AMPK-CPT pathway after ERα agonist.

Reduced expression of endothelial nitric oxide synthase (eNOS) in chronic liver disease can reduce hepatic perfusion and accelerate fibrosis. The relationship between eNOS expression and liver fibrogenesis remains unclear. We investigated whether L-arginine attenuated chronic liver fibrosis through eNOS expression. Chronic liver injury was induced by administration of carbon tetrachloride (CCl(4)) to mice for 8 weeks. 5-Methylisothiourea hemisulphate (SMT), an iNOS inhibitor, or L-arginine, a NOS substrate were injected subcutaneously. CCl(4)-induced hepatotoxicity, oxidative stress and accumulation of collagen were detected in the liver. The expression levels of inducible NOS (iNOS) and nuclear factor kappa-B (NF-kappaB) activity in the liver after CCl(4) treatment were increased but eNOS expression and activator protein-1 (AP-1) activity were decreased. Both SMT and L-arginine effectively reduced CCl(4) induced oxidative stress and collagen formation, but L-arginine showed a significantly greater suppression of collagen formation, iNOS expression and NF-kappaB activity. L-arginine also restored the level of eNOS and AP-1 activity. L-arginine was more effective than SMT in suppressing liver fibrosis. L-arginine might improve NO production which facilitates hepatic blood flow and thus retards liver fibrogenesis. Our results showed that the reduced eNOS expression in CCl(4)-treated mice was reversed by L-arginine. Furthermore, L-arginine also reversed the reduced AP-1 activity, an eNOS promoter.

Background: Macrophage migration inhibitory factor (MIF) has emerged to be a pivotal cytokine in immune-mediated diseases. Patients and methods: To investigate the role of MIF in chronic hepatitis B infection, we studied two groups of hepatitis B surface antigen positive patients: group 1 (immune tolerant, n=16) and group 2 (immune clearance, n=16). Serum level of MIF was measured by enzyme-linked immunosorbent assay and intrahepatic expression of MIF, macrophage and T-cell localisation were detected by double immunohistochemistry. Results: An increased serum MIF correlated significantly with increased serum alanine aminotransferase activity (r=0.73, P

This article represents the proceedings of a symposium at the 2002 ISBRA/RSA meeting in San Francisco, USA. The organizer and chair was H. Ishii and co-chair was A.A. Nanji. The presentations were (1) Introduction: Apoptosis in alcoholic liver disease, by A. A. Nanji; (2) Mitochondria, oxidative stress and apoptosis in alcoholic liver disease, by M. Adachi; (3) Regulation of cell death by mitochondrial glutathione, by J.C. Fernandez-Checa; (4) Toxicity of ethanol in HepG2 cells that express CYP2E1, by A.I. Cederbaum; (5) Is alcohol-enhanced liver apoptosis a pathogenic factor in alcoholic liver disease? by I.V. Deaciuc.

The article summarizes the proceedings of a symposium on recent advances in research on the pathogenesis of alcoholic liver disease at the 2001 RSA meeting in Montreal, Canada. The chairs were Amin A. Nanji and Samuel W. French. The presentations were (1) Role of inflammatory mediators in alcoholic liver injury by Amin A. Nanji, (2) Role of endotoxin, lipopolysaccharide binding protein, CD14 and Toll receptors in alcoholic liver injury by Grace Su, (3) Fatty acid ethyl esters: toxicity, metabolism and markers of ethanol intake by Michael Laposata, and (4) Cyclic changes in gene expression when rats are fed alcohol at a constant rate by Samuel W. French.

Essentially all patients with significant alcoholic liver disease (ALD) have clinical manifestations of malnutrition. 101 Work by Lieber and others, however, has demonstrated that ALD can occur despite adequate nutrition. 85,86 This suggests that the liver injury of ALD is attributable to direct toxic effects of alcohol and its metabolites or the consequences of alcohol metabolism. Major research efforts into these areas have uncovered several potential mechanisms that may play a role in the liver injury of ALD. In all likelihood, several mechanisms operate simultaneously to initiate, potentiate, or perpetuate liver injury once it is initiated in clinical ALD. In addition, the initiating events or factors in alcoholic liver injury and the reasons why some individuals are predisposed to ALD are not known. Although interesting data recently were reported on the mechanisms of liver fibrosis in ALD, alcoholic hepatitis (AH) and acute liver injury are the foci of our discussion because most investigators agree that AH is an intermediate but potentially reversible stage of ALD. It is hoped that further knowledge concerning the pathogenesis of AH will allow the development of more effective treatments for this potentially lethal disease. The concepts of liver injury caused by alcohol-related oxidative stress (lipid peroxidation), immune response (cytokines), fatty acid metabolites, acetaldehyde production (protein–acetaldehyde adduct formation), mitochondrial dysfunction, and synergism of viral liver injuries, have been proposed. 81,145 These are the areas that have received major investigative attention over the past decade and are reviewed in this article.

We used the intragastric feeding rat model for alcohol liver disease to investigate the relationship between endothelin and pathologic liver injury. Rats were fed the following diets for periods of 1, 2 and 4 weeks: corn oil plus ethanol (CE), corn oil plus dextrose (CD) and saturated fat plus ethanol (SE). Plasma endothelin levels were significantly higher in the CE group compared to the other groups at all time periods studied. The CE animals, also, developed pathologic liver injury which is in contrast to the SE and CD animals which showed no pathologic changes. We propose that endothelin, because of its powerful vasoconstrictive effects, leads to a reduction in hepatic blood flow which is important in the pathogenesis of alcoholic liver disease.

The variety of animal models used in the study of alcoholic liver disease reflects the formidable task of developing a model that replicates the human disease. We show that oral feeding of fatty acids derived from fish oil and ethanol induces fatty liver, necrosis, inflammation, and fibrosis. Together with the study of oxidative and nitrosative stress markers, cytokines, proteasome function, and protein studies, this model has provided an inexpensive and technically simple method of establishing pathological alcoholic liver injury.

As occurs in people, nonalcoholic fatty liver disease (NAFLD) is associated strongly with obesity, diabetes, and dyslipidemia in experimental animals. There are many animal models that have been used to investigate the pathogenesis of nonalcoholic fatty liver disease. Most of this work has used mice or rats that are fed diets high in fat or carbohydrates, or mice that exhibit a genetic deficiency of a satiety factor such as leptin, 5-adenosylmethionine,or enzyme deficiencies in fatty acid oxidation. The purpose of this article is to update information regarding animal models in the pathogenesis of NAFLD.

Endotoxemia and oxidative stress activate nuclear factor kappa B (NF-kappaB) in alcoholic liver injury. In alcohol-fed rats, activation of NF-kappaB is associated with the development of necro-inflammatory changes in the liver. Whether activation of NF-kappaB occurs prior to development of liver injury is unknown. We determined whether activation of NF-kappaB preceded histopathological liver changes. Male Wistar rats were fed a liquid diet containing ethanol by continuous infusion through permanently implanted gastric tubes. Radical intermediates detected by spin trapping were measured in bile prior to killing. After 2 weeks of treatment, samples of liver tissue were obtained for histopathological examination, for evaluation of NF-kappaB, and determination of messenger RNA levels of cytokines, chemokines and cyclo-oxygenase-2. No pathological changes in liver were seen after 2 weeks of intragastric feeding. However, activation of NF-kappaB was seen in the livers from ethanol-fed rats. In addition, elevated mRNA levels of hepatic pro-inflammatory cytokines (TNF-alpha and IL12), chemokines MIPIalpha and MIP-2) and cyclo-oxygenase-2 were seen in association with activation of NF-kappaB and increased levels of free radicals and endotoxin. Thus, activation of NF-kappaB, associated with elevated mRNA levels of pro-inflammatory stimuli, precedes the histopathological liver changes in experimental alcoholic liver disease in rats.

We have previously shown a relationship between plasma endotoxin levels and severity of alcoholic liver injury in the intragastric feeding rat model. We attempted to reduce both circulating endotoxin and liver injury in this model by administering a lactobacillus strain (species GG) which survives for prolonged periods in the gastrointestinal tract. Male Wistar rats were fed ethanol and liquid diet containing corn oil (CO+E). Another group of animals (CO+E+L) received the diet containing ethanol plus a daily bolus of lactobacilli GG concentrate (10(10) CFU). All animals were sacrificed after one month. All animals had plasma endotoxin measurements and evaluation of severity of pathologic changes in the liver. The weight gain and blood alcohol levels were similar in both groups. The mean +/- SE of the pathology score was significantly higher (3.4 +/- 0.85) in the CO+E group compared to the CO+E+L group (0.5 +/- 0.3, P < 0.01). The virtual absence of pathologic changes in the latter group was accompanied by significantly lower endotoxin levels (8.4 +/- 2.9 pg/ml in CO+E+L group vs 48.3 +/- 7.8 pg/ml in CO+E group, P < 0.01). Feeding of strains of lactobacilli that survive in the gastrointestinal tract reduces endotoxemia and alcohol-induced liver injury in the rat. Lactobacillus species GG provides a potential nontoxic form of therapy for both endotoxemia and alcoholic liver disease.

We used the intragastric feeding rat model for alcoholic liver disease to investigate the relationship between prostacyclin and liver injury. Rats were fed the following diets for periods ranging from 1 to 8 weeks: corn oil plus ethanol (CO+E), corn oil plus dextrose (CO+D), saturated fat plus ethanol (SF+E) and saturated fat plus dextrose (SF+D). Prostacyclin production (assessed by 6-ketoprostaglandin F1 alpha) by liver non-parenchymal cells decreased steadily over the 8 week period in animals fed CO+E (liver injury present) whereas in animals fed SF+E (no liver injury) there was no change in prostacyclin production. Plasma levels of 6-ketoprostaglandin F1 alpha were also significantly lower in the CO+E group compared to the other groups studied. We propose that decreased prostacyclin production by liver non-parenchymal cells may contribute to the hepatotoxic effect of ethanol.

The authors evaluated the quality and reliability of four desktop analyzers in the outpatient clinic. Twenty-seven nontechnologists (NTs) participated in the study. These included nurses, physicians, and medical students. The instruments and tests evaluated were as follows: Reflotron (glucose, cholesterol, triglycerides, gamma-glutamyltransferase and urea); Seralyzer (creatinine, glucose, potassium, aspartate aminotransferase, and hemoglobin); Vision (glucose, urea, cholesterol, triglycerides, alkaline phosphatase, and uric acid); and DT60 (sodium, potassium, glucose, amylase, uric acid, bilirubin, and creatinine). For precision studies, low and high control material was used, and method comparison was done with methods in routine use in the laboratory. The range of coefficients of variation (CVs) for the analyzers with NTs was as follows: Reflotron: CV, 2.4-7.9%; Seralyzer CV, 1.4-18.7%; Vision: CV, 1.5-2.7%; DT60: CV, 2.5-46.8. The percentage results that is different by greater than 10% between the NTs and trained technologists was related to the complexicity of procedure for each analyzer and was the lowest for the Vision analyzer and greatest for the Seralyzer.

A case of chlorambucil overdose is presented. The clinical manifestations were acute renal failure and seizures. We are not aware of this combination of clinical features being previously reported with chlorambucil overdose.

We evaluated whether arterial blood samples for pH and blood gas analysis need to be transported on ice. We found that although the changes in pH, pCO2 and pO2 were greater in samples kept at room temperature versus those kept on ice, the difference was probably not of clinical significance until the period of time after arterial puncture exceeded 20 minutes. We recommend that arterial blood samples do not need to be kept on ice if the analysis for pH and gases is performed within 20 minutes of blood being drawn.

We report a case of autoimmune hemolytic anemia, in a 28-year-old man with a warm-reacting IgG antibody with anti-Sdx activity. The unusual characteristics of the patient included the drama

We have compared the incidence of inflammatory bowel disease (IBD) to the prevalence of lactose malabsorption (LM) in several countries. Our observations indicate that IBD is rare where LM is highly prevalent. The correlation between incidence of Crohn's disease and LM is -0.93, p less than 0.01, the correlation between incidence of ulcerative colitis and LM is -0.89, p less than 0.01. We, therefore, propose that LM results in the formation of volatile fatty acids which may inhibit multiplication of potentially pathogenic organisms.

The diagnosis of septic infections of closed body cavities requires a careful search. Traditional laboratory tests such as Gram's stain, white cell count, and protein and glucose levels are often inconclusive. Measurement of lactic acid in cerebrospinal, synovial, pleural, ascitic, and bursal fluids has been utilized to distinguish bacterial from nonbacterial infections. The present review summarizes the current status of lactic acid measurement in the differential diagnosis of meningitis, arthritis, empyema, bacterial peritonitis, and bursitis.

We investigated the possibility that organs other than liver in women were more susceptible to alcohol than in men. Female:male cirrhosis mortality ratio in different countries was used as an index of female susceptibility to alcohol. The F:M cirrhosis ratio correlated significantly with F:M ratios for cerebrovascular disease and cancers of the esophagus, liver and lung. This preliminary evidence suggests that other organs and/or disease processes in women may be affected more by alcohol than in men.

We evaluated a novel, rapid, noninvasive method of skin surface air sampling that detects the presence of nicotine and therefore can identify smokers. The principle of the methodology involved is skin surface air sampling and ion-mobility spectrometry. We studied 93 volunteers and patients; 50 of these gave a positive history for smoking. Skin surface sampling identified 49 of these 50 individuals. Fifty of the 93 individuals provided urine samples. Nicotine was detected in 22 of these urine samples by thin-layer chromatography. Skin surface sampling identified all of these patients. The combination of skin surface air sampling and ion-mobility spectrometry is a rapid, noninvasive screening method for separating smokers from nonsmokers.

Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue-platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney.

We have evaluated the use of a novel method for detecting drug residues on the hands of emergency patients suspected of drug overdose. The residues are collected by means of a suction probe and subsequently analyzed by thermal desorption directly into an ion mobility spectrometer. All patients admitted to the Emergency Room had their palms, fingers and nostrils sampled. Of the 101 drug related ingestions, 50 were related to tablets, 47 to film or sugar-coated tablets and 4 to cocaine powder. Positive identification was possible in 42% of tablet related ingestions, 29% of coated tablet or capsule ingestions and in all patients using cocaine. In 53% of the cases where positive drug identification was made, sampling had been carried out within 30 minutes of the patient's arrival at the Emergency Room.

Platinum concentrations were determined in autopsy tumor samples obtained from 27 patients who had received cisplatin 40-1,029 mg/m2 from 0 to 240 days antemortem. Liver metastases had significantly higher platinum concentrations than did tumors in other sites (p less than 0.005). Platinum concentrations in liver metastases were similar to platinum concentrations in normal liver. Platinum concentrations in gliomas and brain metastases were similar to platinum concentrations in other extrahepatic tumors. Platinum concentration generally decreased with increasing distance into brain from tumor. By multiple stepwise linear regression analysis, the factors that were independently most closely associated with tumor platinum concentration were time from last cisplatin treatment, cumulative lifetime dose of cisplatin, route of cisplatin administration (intraarterial vs. other), and site of tumor deposit (liver vs. other) (r = 0.69, p less than 0.001). Patients whose tumors had responded to cisplatin-containing regimens had mean tumor platinum concentrations that were higher than the mean tumor platinum concentrations in patients whose tumors had not responded to cisplatin (p less than 0.05).

We evaluated the quality of results obtained for near- patient testing by residents and interns (MDs) using desk-top analyzers. The instruments evaluated were the Reflotron analyzer, the Seralyzer, the Vision analyzer, and the Kodak DT60 analyzer. Low- and high-concen trations of control materials were used for precision studies. Results obtained by MDs were compared with those obtained by a trained technologist for comparison studies. The range of precision obtained by MDs was 4.6 to 6.6% for the Reflotron analyzer, 3.6 to 20.7% for the Seralyzer, 1.7 to 5.3% for the Vision analyzer, and 2.7 to 13% for the Kodak DT60 analyzer. The range of correla tion coefficients for each of the analyzers was 0.980 to 0.994 for the Reflotron analyzer, 0.763 to 0.933 for the Seralyzer, 0.989 to 0.999 for the Vision analyzer, and 0.987 to 0.999 for the Kodak DT60. The percentage of results for each of the analyzers when the results ob tained by MDs were more than 10% different from the trained technologist's results were 17.3% for the Reflo tron, 44% for the Seralyzer, 0% for the Vision, and 17% for the Kodak DT60. The discrepancies between MD and the trained technologist's results are related to the complexity of the instruments used.

We evaluated changes in serum albumin concentrations in 15 patients with advanced malignancy who were also receiving cisplatin. All 15 patients had serial measurements of serum albumin. The decrease in serum albumin from the time of the first dose of cisplatin to death correlated with liver platinum levels at autopsy (r = 0.46, p less than 0.05). The decrease in serum albumin concentration associated with liver platinum concentration of less than or equal to 1.5 micrograms/g was 0.16 +/- 0.23 g/dl (range 0-0.6). The decrease associated with liver platinum concentrations of greater than 1.5 micrograms/g was 1.0 +/- 0.45 g/dl (range 0.5-1.9; p less than 0.02). The decrease in serum albumin may be secondary to a hepatotoxic effect of cisplatin.

Mortality from cirrhosis in many countries deviates markedly from that expected for a given per capita alcohol intake. Since lipid peroxidation is thought to be one of the mechanisms involved in the pathogenesis of liver disease and since uric acid is a natural antioxidant, we investigated the possibility that deviation in mortality rates from cirrhosis in different countries might be related to serum uric acid levels in the populations studied. Deviations from expected cirrhosis mortality were calculated as a percentage and correlated with the serum uric acid levels in nine countries. Since animal protein is a major source of dietary purines, the percentage deviation was also correlated with animal protein intake (g/capita/day) for 15 countries. Significant Pearson r correlations were obtained between the percentage deviation in cirrhosis mortality and serum uric acid (-.70, p less than .05) and animal protein ingestion (-.67, p less than .02). This suggests that higher levels of serum uric acid or higher intake of protein may protect against the development of cirrhosis.

Unusual elevations of serum creatinine (S-CR) out proportion to increases in serum urea nitrogen (S-UN) are frequently observed in patients with diabetic ketoacidosis when S-CR is measured by the Jaffe end-point reaction. This has been ascribed to interference from acetoacetate but this is not however observed with kinetic DuPont ACA methodology. Eighteen patients with diabetic ketoacidosis were studied: SCR measurements were done using the end point Technicon SMA 6/60 method (Group a, 10 patients) or the kinetic DuPont ACA method (Group B, 8 patients). The values for S-CR in Group A patients (mean value and S-D were 3.3 +/- 1.1 mg/dl) were significantly different from Group B patients (1.6 +/- 0.24 mg/dl) (P less than 0.01). A significant positive correlation was obtained between the "excess anion gap" and S-CR in Group A patients (r = + 0.81, p less than 0.01). The results from two patients in whom serial measurements of S-UN, S-CR and the anion gap were carried out further demonstrate the analytical interference. The study demonstrates that in diabetic ketoacidosis elevated creatinine values measured by an end-point method should not necessarily be interpreted as evidence of significant renal impairment and if possible should be verified by a kinetic method which is free of "ketone" interference.

The relationship between mortality from ischemic heart disease and alcoholic beverage consumption in 27 countries was investigated. A significant inverse correlation was obtained between mortality due to ischemic disease and percent contribution to alcohol consumption by wine (r = -0.75, P less than 0.001). A positive correlation (r = 0.60, P less than 0.001) was obtained between ischemic heart disease and alcohol consumption from beer.

Congestive heart failure usually features a mild to moderate increase in aspartate aminotransferase (AST) activity. A marked increase in AST may occur rarely and is usually preceded by prolonged shock or hypotensive episodes and is accompanied by hyperbilirubinemia. I report two patients with congestive heart failure in whom the AST activity was greater than 8000 U/L. No prior episodes of shock or hypotension occurred in these patients and the accompanying increase in bilirubin was slight. In both cases, the enzyme activity decreased sharply with improvement in the patients' circulatory status. Recognition of this entity is important to distinguish it from viral or drug-induced hepatitis.

A patient with acute liver failure, in whom no infectious, toxic, or other cause of hepatic damage could be found, developed severe hypophosphatemia along with hepatocellular necrosis. We propose that phosphate depletion may be responsible for the liver cell damage, as hypophosphatemia impairs tissue oxygenation and depletes cellular ATP.

The authors studied the relationship between total leukocyte count and body weight in 42 morbidly obese patients (weight range, 101.5-206.8 kg). None of the patients had a recent history of infection, hematologic disorders, chronic respiratory disease, or were smoking more than 5 cigarettes/day. The range of total leukocyte count was 4.2-12.0 X 10(9) cells/L. Twelve of the 42 patients had a leukocyte count of 10 X 10(9) cells/L. There was a significant correlation between body weight (kg) and total leukocyte count (r = 0.68, P less than 0.001). Morbid obesity should be considered as one of the causes of physiologic leukocytosis.

We present a patient with postural hypotension and labile blood pressure due to severe hypophosphatemia. There was no evidence for other causes of postural hypotension in our patient. The blood pressure abnormalities responded to phosphate replacement.

Mortality from cirrhosis in many countries deviates markedly from that expected for a given per capita alcohol intake. We investigated the possibility that dietary factors might explain the deviation expected and actual mortality rates in different countries. Deviations from expected cirrhosis mortality was calculated as a percentage for 17 different countries, all of whom had carrier rates for hepatitis B virus of less than 2%. The percentage of deviation was correlated with dietary intake of saturated fat, polyunsaturated fat, cholesterol, and also with mortality from ischemic heart disease. The percentage of deviation correlated inversely with dietary cholesterol (r = -0.86, p 0.001) and saturated fat (r = -0.80, p 0.001) and positively with polyunsaturated fats (r = -0.55 p 0.05). This suggests that both saturated fat and cholesterol protect against alcoholic cirrhosis while polyunsaturated fats promote cirrhosis. The correlation between percentage of deviation and ischemic heart disease (r = -0.78, p 0.002) suggests that those factors that promote ischemic heart disease protect against alcoholic cirrhosis.

We evaluated the presence and degree of hypokalemia associated with ticarcillin disodium (ticarcillin) therapy in 16 patients. Four of these patients who received less than 10 grams of ticarcillin did not develop significant hypokalemia, but this condition developed in 6 of 9 patients receiving a daily dose of greater than 18 grams of this drug, and the mean urinary potassium was elevated in this group (mean = 78 mEq/24 hrs). The degree of hypokalemia was correlated with the volume status of the patient as judged by the serum urea nitrogen: creatinine ratio. A positive correlation (r = 0.66, p less than 0.05) was obtained between the two parameters. Hypokalemia did not develop in three patients with the syndrome of inappropriate secretion of anti-diuretic hormone who were receiving more than 18 grams of ticarcillin daily, indicating the absence of a stimulus for sodium conservation. Aggressive potassium and fluid replacement should be considered in patients with hypokalemia associated with ticarcillin therapy.

The relationship between prevalence rates of multiple sclerosis (MS) in several countries and the corresponding per capita consumption of fat, beef and pork was investigated. A significant correlation was obtained between prevalence of multiple sclerosis and fat intake (r = 0.63, p less than 0.01), total meat intake (r = 0.61, p less than 0.01) and pork consumption (r = 0.87, p less than 0.001). There was no significant correlation with beef consumption. The mechanism by which pork intake may increase the risk of developing MS is unknown and deserves further study.

Summary Five cases are presented which demonstrate the various factors contributing to the development of hypokalaemia and the relevant literature is briefly reviewed. Hypokalaemia is a common finding in leukaemia. Proper evaluation, adequate replacement of potassium and careful follow-up are necessary for prevention of potential dangers related to hypokalaemia.