The Oklahoma Postmenopausal Women's Health Study: recruitment and characteristics of American Indian, Asian, Black, Hispanic, and Caucasian women.

Since 1994, the National Institutes of Health has required the inclusion of women and minorities in all of its sponsored clinical research. This study describes a workable recruitment strategy that embraces the National Institutes of Health requirement. We describe the recruitment pattern of the Oklahoma Postmenopausal Women's Study conducted in the general community of Oklahoma City and in surrounding areas that are both urban and rural. For the period 1994 through 1997, 491 postmenopausal women from all racial/ethnic groups in the community have participated in this study. Over 4 years of recruitment, the percentage of minority women in the study population has risen annually from 31% in 1994 to 81% in 1997. The overall percentage of minority women in the study population is currently 63.3%: American Indian, 21.8%; Asian, 3.7%; Black, 14.9%; Hispanic, 9.4%; White/American Indian Blend, 13.6%; and White, 36.7%. The recruitment approach described may be implemented in a variety of research settings. Specific recruitment approaches are described, as well as the distribution of sociodemographic and health behaviors across and within ethnic/racial groups.

Alcoholic beverages as a source of estrogens.

Alcoholic beverages contain not only alcohol but also numerous other substances (i.e., congeners) that may contribute to the beverages' physiological effects. Plants used to produce alcoholic beverages contain estrogenlike substances (i.e., phytoestrogens). Observations that men with alcoholic cirrhosis often show testicular failure and symptoms of feminization have suggested that alcoholic beverages may contain biologically active phytoestrogens as congeners. Biochemical analyses have identified several phytoestrogens in the congeners of bourbon, beer, and wine. Studies using subjects who produced no estrogen themselves (i.e., rats whose ovaries had been removed and postmenopausal women) demonstrated that phytoestrogens in alcoholic beverage congeners exerted estrogenlike effects in both animals and humans. Those effects were observed even at moderate drinking levels.

Effects of ethanol on rat Sertoli cell function: studies in vitro and in vivo.

Chronic alcohol administration to male animals is associated with testicular atrophy and gonadal failure. The Sertoli cell seems to be the first testicular cell injured as a result of alcohol exposure. To investigate the adverse effects of ethanol on testicular and particularly Sertoli cell function, the consequences of in vivo and in vitro ethanol exposure on rat Sertoli cell mRNA and protein levels of transferrin and ornithine decarboxylase were investigated. In vivo, ethanol exposure enhanced the levels of both hepatic and testicular (Sertoli cell) transferrin protein and mRNA. Ethanol exposure also enhanced testicular, but not hepatic, levels of ornithine decarboxylase protein and mRNA. These in vivo findings were confirmed when isolated Sertoli cells were studied in vitro. Specifically, ethanol exposure increased Sertoli cell transferrin protein and mRNA levels. Ethanol exposure increased Sertoli cell ornithine decarboxylase mRNA and protein when cultured in serum-free media, but not when cultured in the presence of serum. These studies demonstrate that ethanol exposure of rat Sertoli cells is associated with alterations in the levels of mRNA and protein that are known to be important in the process of spermatogenesis. These findings add to the body of evidence that suggests that, within the testes, the Sertoli cell may be an important target for ethanol-induced gonadal injury.

Biochemical and 31P-NMR spectroscopic evaluation of immobilized perfused rat Sertoli cells.

Cell immobilization and perfusion are used for physiologic studies of Sertoli cells with phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy and biochemical methods. In this study the 31P NMR spectra of Sertoli cells isolated from 18-to 21-day-old rats and immobilized in agarose threads continuously perfused with oxygenated Dulbecco's modifed Eagle medium were obtained at 81 MHz on an NMR system. Cytosolic Ca2+, intracellular Mg2+, lactate and pyruvate, and oxygen consumption were measured with standard biochemical methods. Perfused Sertoli cells maintain a stable intracellular adenosine triphosphate concentration for more than 10 hours. Sertoli cells placed in cold storage overnight and then subjected to perfusion partially regenerate cellular adenosine triphosphate levels. Sertoli cells consume an average of 4.8 +/- 0.4 nmol O2/min/10(6) cells and maintain average ambient lactate and pyruvate levels of 7.1 +/- 0.8 mg/dl and 0.65 +/- 0.05 mg/dl, respectively, with a lactate/pyruvate ratio in the range 8 to 12. The basal Ca2+(i) of Sertoli cells is 98 +/- 0.7 nmol/L (n = 58), which declines to a level less than 10 nmol/L when the Sertoli cells are perfused with a calcium-free medium. Perfusion of Sertoli cells with a sodium-free medium, with 10(-6) mol/L carbonyl cyanide P-trifluoromethoxy-thenylhydrozone, or with Ca2+ ionophore A23187 at a concentration of 10(-6) mol/L increases the Ca2+(i) to a level of 426 +/- 107 nmol/L, 274 +/- 29 nmol/L, or 282 +/- 57 nmol/L, respectively. A bioreactor for physiologic studies of Sertoli cells in real time with NMR spectroscopy has been developed. These data demonstrate that isolated, immobilized, and perfused Sertoli cells are stable for prolonged periods. In addition, these data suggest that Sertoli cells possess a functional Na+-Ca2+ antiporter and that they sequester extracellular Ca2+ in one or more intracellular compartments.

Effect of alcohol use on allograft rejection rates after liver transplantation for alcoholic liver disease.

Alcoholic liver disease is a major cause of liver disease and has become an ever-increasing indication for liver transplantation (LTx). Follow-up studies have reported a higher rate of alcohol recidivism in patients transplanted for alcoholic hepatitis, compared with those transplanted for endstage alcohol-associated cirrhosis. It is assumed widely that recurrent alcohol use is associated with reduced compliance with immune suppression and, as a result, an increased risk of graft rejection and loss. To assess this question, 209 alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with a mean follow-up of 4.4 +/- 0.6 years. There were 175 episodes of acute cellular rejection (ACR) that occurred in 137 patients, for an overall rejection rate of 83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was three times as great in those who remained alcohol-abstinent (2.24 episodes/patient), compared with those who admitted to continued alcohol use (0.75 episodes/patient) (p < 0.01). A total of 33 episodes of chronic rejection occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR, the chronic rejection rate was greater among those who were continuously alcohol-abstinent, compared with those who intermittently used alcohol after successful LTx. There were no differences in the mean FK 506 or cyclosporin A levels in the groups with and without a rejection episode at the time the rejection episode was documented by liver biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxemia is associated with renal dysfunction in liver transplantation recipients during the first postoperative week.

The effect of endotoxemia on renal function was studied in 76 orthotopic liver transplant patients. In the preoperative period, a high preoperative serum creatinine level (> 2.0 mg/dl) was significantly associated with postoperative endotoxemia. The serum total bilirubin level was significantly greater in the patients with high serum creatinine levels than in those with lower serum creatinine levels (< 2.0 mg/dl). On the 7th postoperative day (POD), the serum creatinine level was significantly associated with an increased plasma endotoxin level. The serum total bilirubin and AST levels did not differ significantly between the patients with high and those with low serum creatinine levels. Based upon these data postoperative endotoxemia is suspected as being the principal cause of early postoperative renal dysfunction. A synergistic effect on renal function between cyclosporine and endotoxin may be important in the pathogenesis of the renal dysfunction seen after successful liver transplantation.

Aggressivity among sons of substance-abusing fathers: association with psychiatric disorder in the father and son, paternal personality, pubertal development, and socioeconomic status.

An association between childhood aggression and risk for subsequent development of a substance abuse disorder is now well-accepted. In order to better understand the relationship between the presence of paternal substance abuse and aggression among their offspring, 10-12 year old sons of fathers with (n = 34) and without (n = 39) a history of a substance abuse disorder were contrasted on demographics, aggressivity, biological indices of reproductive maturation, and the presence of psychiatric diagnoses. In addition, personality factors, the potential for physical abuse, and psychiatric diagnoses were also ascertained among their fathers. Sons of substance-abusing fathers were found to be significantly more aggressive than sons of nonsubstance abusers. However, they also differed from comparison boys on the basis of SES and school grade attained, as well as the proportion with specific psychiatric disorders. Substance-abusing fathers differed from nonsubstance-abusing men in terms of personality factors and the presence of specific psychiatric disorders, including antisocial personality. They also showed significantly higher child abuse potential scores. A multiple regression analysis of factors contributing to aggression in the boys revealed that a paternal personality factor characterized by stress reactivity, alienation, and aggression was the most robust contributor to aggression among the boys. The boys' diagnoses of attention deficit disorder, oppositional defiant disorder, and lower household socioeconomic status were also significant predictors of aggressivity. Contrary to expectations, paternal, psychiatric diagnoses, substance abuse status, and potential for physical abuse were noncontributory. The results suggest potential mechanisms by which both aggression and risk for substance abuse may be transmitted from father to son.

Cryoglobulinemia: a cause for false negative polymerase chain reaction results in patients with hepatitis C virus positive chronic liver disease.

With the introduction of interferon therapy for liver disease due to chronic viral hepatitis, it has become important to test individuals thought to have hepatitis C virus disease for the presence of the virus. Moreover, the current goal of therapy for hepatitis C virus-positive liver disease is to render the individual patient HCV-RNA negative. Recently, it has been reported that as many as one-third of the patients with hepatitis C virus liver disease test positive for the presence of mixed cryoglobulins. Few of these cryoglobulin-positive patients have overt disease manifestations of cryoglobulinemia, such as nephropathy, peripheral neuropathy and vasculitis. Because the cryoglobulins in patients with hepatitis C virus-positive disease are directed at hepatitis C virus epitopes, the precipitation of cryoglobulins from serum samples also effectively removes virus. When the viral carriage rate is low in terms of the number of genomes/unit serum, as occurs in cases that are partially treated, the serum can test negative for hepatitis C virus even by polymerase chain reaction, despite the presence of persistent viremia, if precautions preventing the precipitation of cryoglobulins prior to the removal of the sample for polymerase chain reaction testing are taken. From a group of 75 patients with hepatitis C virus-positive hepatitis seen at our institution in the last year (all HCV-RNA positive), 35% were found to test positive for the presence of cryoglobulins. Importantly, in all cases, the cryoglobulins collected tested strongly positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

The phytoestrogen congeners of alcoholic beverages: current status.

The idea that alcoholic beverages might contain biologically active phytoestrogenic congeners stemmed from findings of overt feminization observed in alcoholic men with alcohol-induced cirrhosis. Specifically, in addition to being hypogonadal, these chronically alcohol-abusing men with cirrhosis frequently manifest gynecomastia, palmar erythema, spider angiomata, and a female escutcheon. These physical signs of exposure to active estrogen occur in the presence of normal or only minimally elevated levels of endogenous steroid estrogens. Because levels of circulating steroid hormones failed to provide a satisfactory explanation for the feminization observed, alternate explanations were considered. If the estrogenization observed was not entirely a function of tissue expose to steroid estrogens produced endogenously, then perhaps tissues were being exposed to exogenous estrogenic substances from dietary sources. Given the degree of alcohol abuse in the population in which hypotheses for feminization were being formed, alcoholic beverages became a prime candidate as a dietary source of exogenous estrogenic substances.

Alcohol effects on hormone levels in normal postmenopausal women and in postmenopausal women with alcohol-induced cirrhosis.

The effects of alcoholic beverage consumption on the hormonal status of postmenopausal women will be reviewed. Focused attention on the effect of social drinking 244 normal postmenopausal women has revealed that moderate alcohol intake exerts a major influence not only on estradiol, testosterone, and the estimate of aromatization of testosterone to estradiol but also on the estrogen-responsive pituitary hormones in normal postmenopausal women. The hormonal status of 66 postmenopausal women with alcohol-induced cirrhosis is compared with normal alcohol-abstaining control women. As expected, there are significant differences in levels of all hormones; furthermore, hormonal interrelationships are also disrupted. Of major interest are findings that hormone levels in alcoholic cirrhotic postmenopausal women are related to the severity of liver disease. This observation supports a role for cirrhosis per se in the hormonal disruptions noted. Of further interest are findings that hormone levels may have prognostic value in postmenopausal women with alcohol-induced liver disease.

Liver transplantation for neonatal hepatitis as compared to the other two leading indications for liver transplantation in children.

Neonatal hepatitis is a syndrome of unknown etiology occurring in children with viral liver disease, as well as children with unidentified disorders of bile salt synthesis and other poorly understood metabolic diseases. It is characterized by jaundice, giant cell hepatitis and rare liver failure necessitating liver transplantation. In the present investigation, the outcome of liver transplantation performed in 16 children with neonatal hepatitis at the investigators' institution was determined from 1 January 1989 to 31 December 1991. The results were compared to those obtained in 288 children transplanted for biliary atresia and 66 children transplanted for recognized metabolic liver disease. The children transplanted for neonatal hepatitis (4.1 +/- 1.3 years) and metabolic liver disease (5.8 +/- 0.6 years) were older than those transplanted for biliary atresia (3.3 +/- 0.2 years) (p < 0.01), but did not differ in terms of sex, ABO type, UNOS status or year in which the transplant procedure was performed. Interestingly, first allograft survival was equal in the children with neonatal hepatitis (74%) and those with metabolic liver disease (74%), but was greater than that for children transplanted for biliary atresia (68%) (p < 0.01). Despite this significant difference in first graft survival, no differences in 5-year survival were seen for the three groups (81% for neonatal hepatitis, 68% for biliary atresia and 79% for metabolic liver disease).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of granulocyte-macrophage colony-stimulating factor to enhance hematologic parameters of patients with cirrhosis and hypersplenism.

In patients with end-stage liver disease complicated with hypersplenism, neutropenia and thrombocytopenia are risk factors for systemic sepsis and spontaneous bleeding. Granulocyte-macrophage colony-stimulating factor is a naturally occurring cytokine that promotes proliferation and differentiation of granulocyte and monocyte progeny cells. In addition, it is reported to promote the proliferation of megakaryocytes. Its use as an intravenous infusion is Federal Drug Authority (USA) approved for the enhancement of myeloid recovery following autologous bone-marrow transplantation. The present study was initiated to determine whether granulocyte-macrophage colony-stimulating factor could be used to increase the white blood cell and platelet count in patients with cirrhosis and hypersplenism and to determine whether the more convenient subcutaneous route can be used with the same efficacy as the recommended intravenous route. Nine patients with cirrhosis and hypersplenism manifested by a reduced absolute neutrophil count (mean value of 1300 +/- 200/mm3) were studied. In eight patients, Indium white blood cell splenic sequestration scans were obtained before and after the administration of granulocyte-macrophage colony-stimulating factor intravenous infusion or subcutaneously for 7 days. One patient had to discontinue the therapy due to a reaction to granulocyte-macrophage colony-stimulating factor. Following intravenous infusion of granulocyte-macrophage colony-stimulating factor, the mean absolute neutrophil count increased to 2600 +/- 1100/mm3. Following subcutaneous administration, the mean absolute neutrophil count increased to 4100 +/- 200/mm3. No significant change in platelet count occurred with either route of administration. Indium scans obtained before and after the treatment period revealed no significant difference in the splenic uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of putative non-A, non-B, non-C hepatitis with alpha interferon: a preliminary trial.

Chronic hepatitis due to putative non-A, non-B, non-C hepatitis occurring in an individual who is negative for HBV and HCV markers has been identifiable only recently. Little or nothing is known about its natural history or response to interferon therapy. In the present study, 13 subjects with chronic non-A, non-B, non-C hepatitis were treated with interferon for 6 months (5 million units, three times per week). Prior to and after 6 months of therapy and again 6 weeks after discontinuing interferon therapy, each subject underwent a liver biopsy. These tissues were used to define the histopathology, the character of the cellular infiltrate within the liver, and the changes in histopathology and inflammatory infiltrate achieved in response to interferon therapy and withdrawal. No differences for age, gender, initial AST, bilirubin, histopathology, or Knodell score were evident between responders (n = 7) and non-responders (n = 6). Only the number of NK cells was altered significantly as a result of IFN treatment and distinguished responders from non-responders. These data demonstrate that: (1) chronic non-A, non-B, non-hepatitis can be treated with interferon; (2) interferon activates NK cells and enhances hepatocyte expression of Class II MHC antigens; and (3) interferon also increases the number of CD3, CD4, and CD8 cells found within the liver but these changes do not distinguish between responders and non-responders.

Unusual indications for liver transplantation.

This paper is an attempt to present some of the unusual indications for OLTx that are occasionally seen at transplant centers. It is not an all-encompassing treatise but rather an attempt to present the more usual of the unusual indications for OLTx. As such, it is a framework to which readers could add any we do not mention as and when they are encountered in their own practice.

Rheumatoid arthritis: a complication of interferon therapy.

A case report of rheumatoid arthritis developing during alpha-interferon therapy of chronic hepatitis C is reported. The rheumatoid arthritis was severe, being non-responsive to the use of nonsteroidal anti-inflammatory drugs, and persisted despite discontinuation of the interferon therapy. The literature relative to this case suggesting an association between rheumatoid arthritis and interferon therapy is presented. This case suggests that interferon therapy may precipitate subclinical rheumatoid arthritis in an individual without pre-existing clinical arthritis.

Intrahepatic mononuclear cell populations and MHC antigen expression in patients with chronic hepatitis C [correction of B]: effect of interferon-alpha.

Twenty-four subjects with chronic HCV infection were treated with IFN for six months. Liver biopsies were obtained before and after therapy. The number of mononuclear cells staining for CD3, CD4, CD8, 3G8, and the number of mononuclear cells, liver cells, and bile duct cells staining for class I and II MHC antigens in the biopsies was determined. NK cells increased from 16 +/- 3 to 28 +/- 3 cells per 5 high-power fields (HFP) (P < or = 0.03). The number of bile duct cells expressing class I and II MHC Ag and liver cells expressing class II MHC Ag increased (all P < or = 0.03). The only parameter that distinguished responders from nonresponders was the number of NK cells. Following IFN withdrawal, expression of these antigens declined. Based upon these data, it is concluded that IFN treatment of HCV increases: (1) the NK cells number; (2) the expression of class I MHC Ag on bile duct cells and the expression of class II MHC Ag on liver and bile duct cells; and (3) with IFN withdrawal, these changes disappear.

Sexuality of alcoholic postmenopausal women: effects of duration of alcohol abstinence.

Little is known about the sexuality of alcoholic postmenopausal women, and even less is known about the influence of abstinence on self-assessed measures of sexual function. We now report findings in 60 postmenopausal women to whom a standardized questionnaire was administered. The responses provided information related to not only perceptions of sexuality, but also sexual behavior and performance. Women were categorized as alcohol abstinent (AA) for > 1 year (long AA, n = 33) or < 1 year (short AA, n = 27). There were no differences between the groups in age, age at menarche, age at menopause, or age at onset of heavy drinking and alcohol dependence. The mean response rate to 12 sexuality-related questions was comparable in the long AA and short AA groups (83.8% and 85.6%, respectively), and reflected the prevalence of having a regular sexual partner (76% and 85%, respectively). There were statistical differences between the two groups with respect to sexual desire, arousability, and responsiveness during alcohol abstinence, but not during alcohol dependence. Further, there were significant differences with respect to measures of current sexuality: higher proportions of long AA women reported sex being important, as well as their sexual life and intercourse being satisfying. Taken together, these findings suggest that alcoholic postmenopausal women abstinent from alcohol for longer than 1 year report greater satisfaction with the sexual aspects of their lives than women abstinent for a shorter period of time.