Predictors of medical examinations following child and adolescent rapes in a national sample of women.

Childhood rape occurs frequently in our society and is associated with adverse consequences. Despite the severity of these outcomes, there appear to be many obstacles for children to receive postrape medical care. To date, it is unclear what proportion of childhood rape victims receive postrape medical examination or what factors predict receipt of this medical care. This study instigated the factors predicting immediate medica care for women who were raped during childhood. Data for the study were obtained from the final wave of the 2-year, longitudinal National Women's Study. Results indicated that the majority of women did not receive medical care following their childhood rape. Although women raped as adolescents were more likely to receive a postrape exam, logistic regression analyses indicated that rape characteristics (e.g., reporting the assault, concerns about sexually transmitted diseases [STDs]) mediated the relationship between age of victimization and receipt of medical care. Implications of these findings are discussed.

Impact of childhood rape and aggravated assault on adult mental health.

Associations among childhood assault (rape, aggravated assault, or both) and indices of adult mental health (posttraumatic stress disorder, major depressive episode) were examined in a national probability sample of 4,008 (weighted) women. Relationships among assault characteristics and these adult mental health indices were also investigated. Findings suggested particularly deleterious effects for childhood aggravated assault and rapes that caused additional physical injury.

Reactive Attachment Disorder: what we know about the disorder and implications for treatment.

In recent years, there has been an increase in the number of children diagnosed with Reactive Attachment Disorder (RAD). There is considerable disagreement about what this entity actually entails and, in particular, what types of assessments and interventions to use with these children and families. Children with a history of maltreatment (i.e., physical, sexual, emotional abuse, and/or severe neglect) are particularly likely to receive this diagnosis, because the behavior problems often seen in these children are presumed to stem from the maladaptive relationships they have had with abusive caregivers. However, many children are receiving this diagnosis because of behavior problems that clearly extend beyond the DSM-IV criteria for RAD. Perhaps the most concerning consequence of the RAD diagnosis is the emergence of novel treatments that lack a sound theoretical basis or empirical support, and may potentially be traumatizing and dangerous to the child. Thus, the purpose of this article is to review and synthesize what is known about RAD and attachment disorders and to discuss implications for treatment.

Factors related to the reporting of childhood rape.

OBJECTIVE: The aim of this study was to examine whether there would be differences in reported versus unreported cases of childhood rape on incident characteristics including life threat, physical injury, identity of the perpetrator, frequency of assault(s), and rates of posttraumatic stress disorder or major depression. METHOD: In a telephone interview, a national probability sample of 4,008 (weighted) adult women was screened for a history of completed rape in childhood. Respondents were also assessed for DSM-III-R diagnoses of major depressive episode and/or posttraumatic stress disorder (PTSD). Three hundred forty-one (8.5%) of these women were victims of at least one rape prior to the age of 18, for a total of 437 completed rapes. Of these 437 rape incidents, 52 (11.9%) were reported to the police or other authorities. RESULTS: Significant differences were obtained between reported versus nonreported cases on incident characteristics, including life threat, physical injury, identity of the perpetrator. Reported cases were more likely to involve life threat and/or physical injury, and were more likely to have been committed by a stranger than nonreported cases. No significant differences between reported and nonreported cases were found concerning whether the rape involved a single incident versus series of events, or rates of PTSD or major depression. CONCLUSIONS: Findings suggest that different characteristics are associated with reported versus unreported cases of childhood rape. Since few cases of childhood rape are actually reported to the authorities, it appears that we may be missing valuable information. Implications for research and clinical intervention are discussed.

Childhood physical assault as a risk factor for PTSD, depression, and substance abuse: findings from a national survey.

A national sample of adult women was screened for a history of serious physical assault in childhood, major depressive episode, post-traumatic stress disorder, and substance abuse. Approximately 2.6% reported having experienced serious assaults in childhood, with fathers and stepfathers identified as having been the most frequent offenders. Compared to women reporting no such victimization, these women experienced more lifetime and current episodes of depression, post-traumatic stress, and substance abuse.

Los Angeles County after the 1992 civil disturbances: degree of exposure and impact on mental health.

The impact of the 1992 Los Angeles (L.A.) civil disturbances on psychosocial functioning was assessed as part of a larger project investigating the views and attitudes of residents in L.A. County. Random digit dialing methodology identified a household probability sample of 1,200 adults (age 18 or older) from L.A. County. Respondents completed a telephone interview 6 to 8 months after the disturbances. Respondents' degree of exposure to the disturbances, mental health impact of the disturbances, and mental health effects of chronic versus acute exposure to violence were assessed. Consistent with hypotheses, the impact of the disturbances was the worst in the South Central communities. Higher rates of posttraumatic stress disorder (PTSD; both diagnostic level and subclinical symptomatology) were found among respondents who reported disturbance-related experiences. Exposure to an acute event (i.e., the disturbances) was predictive of current PTSD symptomatology after controlling for demographics, lifetime trauma, and other types of stressful events.

Low-dose chenodiol to prevent gallstone recurrence after dissolution therapy.

Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.

Additional chenodiol therapy after partial dissolution of gallstones with two years of treatment.

During the National Cooperative Gallstone Study, therapy with chenodiol, 750 or 375 mg/d, for 2 years resulted in confirmed, complete gallstone dissolution in 14% and 5% of patients, respectively, and partial dissolution (greater than 50%) in 27% and 18%. The present study was done to determine the frequency with which complete dissolution occurs in patients having partial dissolution of gallstones who receive additional therapy. Eighty-six of one hundred thirty-eight eligible patients continued to receive 750 mg/d (61 patients) or 375 mg/d (25 patients) of chenodiol for 1 year. Patients whose oral cholecystogram at the end of the year showed further (greater than 50%) dissolution continued to receive chenodiol, (28 patients at 750 mg/d and 11 patients at 375 mg/d) for a second year (total duration of therapy, 4 years). A final oral cholecystogram was taken at the end of the fourth year. Complete dissolution occurred in 23% and 16% of patients receiving chenodiol, 750 or 375 mg/d, respectively, for an additional 1 or 2 years.

Neonatal cholestatic syndromes associated with alterations in bile acid synthesis.

In summary, the conditions discussed above are examples of diseases that result in deficient bile acid synthesis and production of abnormal bile acids. Although the relationship between the production of these abnormal bile acids and the pathogenesis of these diseases remains unknown, they continue to provide us with a better understanding of normal pathways of bile acid production. Clearly, more studies are needed before these interesting metabolic defects and normal infantile bile acid metabolism itself are well understood.

Pretreatment biliary lipid composition in white patients with radiolucent gallstones in the National Cooperative Gallstone Study.

Biliary lipid classes (bile acids, phospholipids, cholesterol) as well as individual biliary bile acids were measured in duodenal bile samples obtained before treatment from 284 white men and 264 white women participating in the National Cooperative Gallstone Study. The patients had radiolucent gallstones present in visualizing gallbladders. Calculated biliary cholesterol saturation was significantly higher in women (143 +/- 43, mean +/- SD, vs. 132 +/- 39 for men). Chenodeoxycholic acid was the major biliary bile acid in both sexes (40.0 +/- 9.9 in men; 38.8 +/- 9.3 in women, NS). Cholic acid was the second most common bile acid, constituting 32.9 +/- 8.8 in men and 31.8 +/- 8.9 in women (NS). When other demographic and clinical characteristics, including serum lipids, were related with biliary lipid composition, only percent ideal body weight correlated significantly. The partial correlation coefficient adjusted for percent ideal body weight indicated that the proportion of chenodeoxycholic acid correlated negatively with the mole fraction of cholesterol in bile in men, but not in women. Multiple regression analyses showed that bile saturation could not be predicted reliably from any clinical, chemical, or radiologic measurement in either sex. Published data for biliary lipid composition in individuals with biliary disease showed considerable overlap with the National Cooperative Gallstone Study data reported here, suggesting that cholesterol gallstone disease is not caused solely by increased biliary cholesterol saturation.

The effect of hepatic blood flow on taurocholate extraction by the isolated perfused rat liver.

The effect of the rate of portal blood flow on the fractional extraction of the bile salt sodium taurocholate was studied in the isolated perfused rat liver. Thirty-two livers were perfused with a 60 microM solution of taurocholate at flow rates varying from 0.65 to 3.55 ml/min/gm of liver. Extraction was determined from the difference in the concentration of taurocholate in the portal and hepatic vein perfusates. At the low flow rates, the extraction of taurocholate was nearly complete. However, as the rate of perfusion of the portal vein was increased, the extraction of taurocholate decreased exponentially. It is concluded that the single-pass extraction of taurocholate by the liver is related to the rate of sinusoidal flow.

TSH response to TRH in euthyroid, hypercholesterolemic patients treated with graded doses of dextrothyroxine.

In an attempt to determine the minimum dose of D-Thyroxine (D-T4) which will suppress pituitary TSH response to TRH, we have treated 6 euthyroid, hypercholesterolemic patients with graded doses of D-T4. TSH response was suppressed in 3 patients with 3 mg and in the remaining 3 patients with 4 mg D-T4 administered once daily. The mean TSH suppressive dose of 3.5 mg, as determined in this study, is considerably less than the 6 mg daily dose given to patients treated with D-T4 in the Coronary Drug Project. This suggests that the adverse effects observed with D-T4 treatment in the Coronary Drug Project may have been due to mild, undetected hyperthryroidism. D-T4 treatment in our patients was not associated with an increase in heart rate or ventricular ectopic beats as determined by Holter monitoring. However, bile samples obtained at the time of TSH suppression showed a significant increase in lithogenic index. In four patients, TSH suppressive doses of D-T4 were associated with a 12% decrease in mean cholesterol and a 17% decrease in mean LDL cholesterol concentrations.

Competitive inhibition of side chain oxidation of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid by 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid in the hamster.

3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) are metabolized into chenodeoxycholic acid and cholic acid, respectively, through oxidation and cleavage of the terminal three carbons of the side chain. The present study was designed to determine if the same or different side chain oxidation systems are used by these compounds in the bile fistula hamster model. Although a single injection of [3H]THCA is nearly completely metabolized into cholic acid, only about 50% is converted into cholic acid when THCA is infused at a rate of 0.083 mumol/min. The remainder is excreted in the bile unchanged indicating saturation of the side chain oxidation system. Fifty-nine +/- 1.1% (+/- 1SEM) of a single injection of [3H]DHCA is metabolized into chenodeoxycholic acid in bile fistula hamsters infused with either saline or cholic acid at a rate of 0.083 mumol/min. The remainder was excreted as several other metabolic products including cholic acid. However, when [3H]DHCA was administered during an 0.083 mumol/min infusion of THCA, only 39.0 +/- 4.5% of the radioactivity in bile was identified as chenodeoxycholic acid. Thus, this study indicates that DHCA and THCA share at least one of the enzymes involved in side chain oxidation.

Stereochemistry of the side chain oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol in man.

Previous in vitro studies have shown that the oxidation of the side chain of bile acid precursors can start with either microsomal or mitochondrial enzyme systems. The microsomal system oxidizes the terminal methyl group (C-26) of the side chain that originates from C-2 of mevalonic acid, and the mitochondrial system oxidizes the terminal methyl group (C-27) derived from C'-3 of mevalonic acid. We administered [2-14C]-mevalonic acid to a patient with a complete bile fistula and isolated from the bile 3 alpha,7 alpha,12 alpha-trihydroxy[1,7,15,22,26-14C]5 beta-cholestanoic acid, a precursor in the synthesis of cholic acid which has undergone partial oxidation of the side chain. This compound was chemically decarboxylated and the liberated CO2 was trapped and counted. The recovery from control experiments using [24-14C]cholic acid was 82.6 +/- 2.3% (+/- 1 S.D.). However, following decarboxylation of 3 alpha,7 alpha,12 alpha-trihydroxy[14C5]5 beta-cholestanoic acid, only 7.5 +/- 0.58% (+/- S.D.) of the C-26 radioactivity was recovered. This study suggests that the major pathway of side chain oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol starts with hydroxylation of the methyl group derived from C'-3 of mevalonate (C-27) by mitochondrial enzymes. It is also concluded that the 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-27-oic acid formed in man has the R configuration at carbon 25.

Bile acid metabolism in the cirrhotic rat.

Bile acid metabolism was studied in rats with cirrhosis induced by carbon tetrachloride (CCl4). Although the typical histologic features of cirrhosis were seen, cholestasis was not present in these animals as evidenced by a normal total serum bilirubin concentration and by a normal hepatic capacity to remove taurocholate infused intravenously. The cirrhotic rats also secreted taurocholate into bile at a normal rate. The total bile salt pool size in the cirrhotic rats was not significantly different from the pool size in normal rats (10.59 +/- 1.19 mumoles per gm. of liver (+/- 1 standard error of the mean) and 10.43 +/- 0.92 mumoles per gm. of liver, respectively). When the bile was drained externally through a chronic bile fistula, the normal rats increased the bile salt synthetic rate approximately 3-fold after 48 hours of drainage. However, the cirrhotic rats failed to significantly increase the synthetic rate for bile salts in response to biliary drainage. The normal rats also had a significant increase in cholic acid synthesis at the maximal synthetic rate, whereas the cirrhotic rats did not. These findings indicate that (when feedback inhibition is removed) CCl4 cirrhotic rats lack the ability to normally increase the activity of 7 alpha-hydroxylase and 12 alpha-hydroxylase, rate-limiting enzymes in the synthesis of bile salts.

Micellar properties of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oyl taurine and relationship to in vitro red cell disruption.

Patients with a metabolic block in the conversion of THCA to cholic acid develop cirrhosis and hemolysis. Tauro-THCA has been shown to distort hepatic architecture and cause hemolysis in bile-fistula rats. In this study, the critical micellular concentration of tauro-THCA was found to be one fourth of that measured for the primary human bile salt, taurocholate. In short-term incubations with intact red cells, tauro-THCA was more effective than taurocholate in removing red cell membrane lipid, inducing morphological red cell sphering, and decreasing functional cellular membrane surface area. These detergent biological membrane effects were most apparent at a concentration above the critical micellar concentration, with the membrane toxicity of the two bile salts roughly paralleling their differences in critical micellar concentration. The lower critical micellar concentration, greater hydrophobicity, and enhanced surface-active properties of tauro-THCA are speculated on as possible factors contributing to the bile salt's toxicity in vivo.

Formation of cholic acid via 3 alpha, 7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid in the dog.

The proposed cholic precursor, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-[3H]cholestan-26-oic acid, and [14C]cholesterol were infused intravenously at a constant rate into two dogs for 25 days. If the specific activities of trihydroxy[3H]cholestanoic acid and [3H]cholic acid will be equal after an isotopic steady-state is achieved. The specific activities of [14C]deoxycholic acid (formed from [14C]cholic acid) isolated in the stool of these two dogs were equal the last four days of the infusion indicating that labeled deoxycholic acid (and presumably labeled cholic acid) was in an isotopic steady-state. However, the specific activities of trihydroxy[3H]cholestanoic acid were 3.3 and 5.7 times greater than the specific activities of [3H]cholic acid, respectively. These data suggest that either an alternate route of cholic acid synthesis exists exclusive of trihydroxycholestanoic acid or that an isotopic steady state of trihydroxycholestanoic acid cannot be reached during an infusion of labeled trihydroxycholestanoic acid.

Metabolism of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol into cholic acid in normal human subjects.

Side chain oxidation and cleavage of precursors in cholic acid synthesis is thought to involve initial hydroxylation at either position 25 or 26 of the side chain. Therefore, the conversion of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol into cholic acid was studied in normal subjects after single intravenous injections of these labeled alcohols. Eighty-six percent and 82% of 5 beta-cholestane, 3 alpha, 7 alpha, 12 alpha, 26-tetrol was converted into cholic acid in two subjects, respectively. However, only 14 and 16% of the injected 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol was converted into cholic acid in two subjects, respectively. Thus, this study indicates that 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol is an inefficient substrate for cholic acid biosynthesis in man and that the major route of cholic acid synthesis probably involves the 26-hydroxylated intermediate.