The presence of a widened vestibular aqueduct and progressive sensorineural hearing loss in the branchio-oto-renal syndrome. A family study.

OBJECTIVE: A new large family with the BOR syndrome is reported with special reference to the presence of a widened vestibular aqueduct and a progressive sensorineural component in the mixed hearing loss. A review of the BOR literature of 184 patients is given. SETTING: University Hospitals. RESULTS: A BOR family with 17 affected members was studied. Fourteen of those 17 were still alive and 12 of those cooperated in this clinical study. Detailed radiological studies showed in three out of 12 affected family members a widened vestibular aqueduct and progressive sensorineural hearing loss. This raises the question whether there is a true correlation or whether those are coincidental. CONCLUSION: In our family with the Branchio-Oto-Renal syndrome, a widened vestibular aqueduct and progressive hearing loss is found in a few affected family members. Imaging of the temporal bones and long-term audiometric follow-up could help to reveal whether the widened vestibular aqueduct is the cause for the progressive hearing loss.

Psychiatric disorders in sexually abused children.

OBJECTIVE: This study was designed to compare the prevalence of psychiatric disorders in a clinical sample of sexually abused children referred for outpatient evaluation. Two a priori hypotheses were tested: (1) the sexually abused group would have more post-traumatic stress disorder than the non-sexually abused group and (2) non-sexually abused children referred for evaluation would have more diagnoses than the sexually abused group. METHODS: Twenty-six sexually abused children and 23 non-sexually abused children referred for psychiatric outpatient evaluation at a medical school center were matched by age, sex, race, and socioeconomic status and compared to determine differences in prevalence of Axis I, DSM-III-R disorders. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version was used for systematic diagnosis. RESULTS: Groups did not differ significantly in the number of diagnoses and, in both groups, attention-deficit hyperactivity disorder was the most frequent diagnosis. However, the prevalence of post-traumatic stress disorder among sexually abused children was significantly greater (p < .02), with 42.3% of sexually abused children and 8.7% of non-sexually abused children meeting full criteria. There were no significant differences between groups in other diagnostic categories. CONCLUSIONS: This study, using structured interviews and comparison groups, confirmed earlier findings suggesting that sexually abused children are at heightened risk for the development of post-traumatic stress disorder.

Providing culturally appropriate mental health services for minorities.

Research on the use of outpatient mental health services has shown lower rates of utilization by minorities. Barriers include economic considerations, access difficulties, and cultural factors. Promoting the use of outpatient mental health services by minorities can have a positive effect on the overall cost of health and mental health care, as well as increasing access to care and quality of care for minority populations. Advantages and disadvantages of various approaches to providing culturally appropriate programming in mental health services are discussed.

A comparison of male and female clients in substance abuse treatment.

To assess the extent to which women appear to have special treatment needs, this paper compares male and female patients receiving inpatient substance abuse treatment. The author analyzed completed intake interview forms from the files of all clients entering two private, nonprofit inpatient substance abuse treatment facilities during an 8-month period in 1989 (a total of 181 men and 48 women). The women were similar to the men with respect to sociodemographic characteristics, family history, alcohol/drug history, and treatment completion. However, they were more likely to report a sexual abuse history and indicated more emotional distress than the men. Implications for treatment are discussed.

Gastrin releasing peptide antagonists with improved potency and stability.

Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.

High-density functional gastrin releasing peptide receptors on primate cells.

Gastrin releasing peptide (GRP) is a 27 amino acid hormone that elicits a variety of biological effects. Receptor-binding antagonists of GRP may have therapeutic use in several pathologic conditions including cancer. The identification and characterization of GRP receptor antagonists have been aided by the use of murine 3T3 cells that possess functional GRP receptors. However, no human or primate cell lines that possess high-density GRP receptors and exhibit a biochemical or biological response to GRP have been described. To address this problem, we examined a series of cell lines and found that GRP specifically binds to Cos-7 monkey cells and stimulates elevation of intracellular calcium in these cells. Cos-7 cells exhibit a single class of high-affinity (dissociation constant = 0.13 nM) GRP binding sites (35,000/cell). Cross-linking experiments that use radiolabeled GRP identified two species of putative GRP receptor proteins (relative molecular mass, 90,000 and 22,000). Competitive binding inhibition studies indicate that Cos-7 cells tightly bind GRP-specific receptor antagonists. These antagonists block the binding of radiolabeled GRP to Cos-7 cells and inhibit GRP-stimulated elevation of intracellular calcium. These properties make Cos-7 cells a useful reagent for the study of GRP receptor antagonists.

Alcoholism treatment in general hospitals.

This article examines recent developments in the role of general hospitals in providing treatment for alcoholism. It employs data on 5,000 U.S. short-term general hospitals and on all patients discharged from a subsample of 400 of these hospitals in the years 1980 through 1985. The article describes the growth in alcoholism treatment resources in short-term hospitals (1980-85) and examines linked hospital and patient data for the 400 hospitals in the subsample to describe patient diagnoses and resource use (1980 and 1985). Patients are classified by the stage of their alcohol problem, and hospital use is examined for patients in different stages.

Carboxyl-terminal modification of a gastrin releasing peptide derivative generates potent antagonists.

Gastrin releasing peptide (GRP) is a 27-residue peptide hormone which is analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated as an autocrine factor in the growth regulation of small cell lung cancer cells. We have developed a series of potent GRP antagonists by modification of the COOH terminus of N-acetyl-GRP-20-27. The most potent member of this series, N-acetyl-GRP-20-26-OCH2CH3, exhibits an IC50 of 4 nM in a competitive binding inhibition assay. This compound blocks GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts, inhibits GRP-dependent release of gastrin in vitro, and blocks GRP-induced elevation of [Ca2+]i in H345 small cell lung cancer cells. These results demonstrate that while residues 20-27 of GRP influence binding of the parent peptide to its receptor, the COOH-terminal amino acid is primarily responsible for triggering the subsequent biological response.

Minimal antiproliferative effect of recombinant müllerian inhibiting substance on gynecological tumor cell lines and tumor explants.

Múllerian Inhibiting Substance (MIS) is a testicular hormone that promotes involution of the Múllerian duct during embryogenesis. The Múllerian duct gives rise to adult female reproductive ducts including the fallopian tubes, uterus, and upper vagina. Thus, testicular MIS ensures the regression of female sex organ primordia. Partially purified bovine MIS was reported to inhibit proliferation of tumor cells derived from human gynecological cancers. These observations suggest that MIS might be an effective anticancer agent for some human tumors. Recombinant human MIS (rHu-MIS) has recently become available. To assess the antiproliferative activity of rHu-MIS, we examined its effects on 11 ovarian, six endometrial, and two nongynecological human tumor cell lines. rHu-MIS had no effect on proliferation of these cell lines in five independent assays. Forty-three primary human tumor explants were also examined in human tumor colony forming assays, gel-supported primary culture assays, and subrenal capsule assays. rHu-MIS significantly inhibited the growth of five of these tumors including four ovarian and one small cell lung cancer explant. The four ovarian cancer responses include three of 13 (23%) explants tested in human tumor colony-forming assays and one of eight (12.5%) explants tested in gel-supported primary culture assays. We conclude that rHu-MIS may have antiproliferative activity against some human ovarian cancers.

Spontaneously transformed NRK cells lose their mitogenic response to epidermal growth factor.

To understand the relationship between growth factor-induced mitogenesis and spontaneous cell transformation, a clonal isolate of epidermal growth factor (EGF)-responsive NRK cells was passed in vitro until morphologically transformed variants arose. Subclones of EGF responsive (Cl-3) and EGF nonresponsive (Cl-10) NRK cells were isolated. Cl-3 cells grew as flat, contact-inhibited monolayers, while Cl-10 cells grew as rounded or spindle-shaped cells that formed dense foci. Cl-10 cells formed colonies in soft agar more efficiently (p less than 0.01) and formed larger tumors in nude mice (p less than 0.05) than Cl-3 cells. Cl-3 cells exhibited a sixfold increase in DNA synthesis in response to 1.0 nM EGF. Cl-10 cells did not increase DNA synthesis on exposure to 100 nM EGF. These different responses to EGF occurred despite similar numbers of receptors and similar receptor.binding affinities for EGF (Cl-3: 7000 receptors, Kd = 0.67 nM; Cl-10: 8000 receptors, Kd = 0.72 nM). No evidence of transforming growth factor-alpha was detected in either of these cell lines using Northern blots, Western blots, or biologic assays. We conclude that NRK cells which undergo spontaneous morphologic transformation and exhibit enhanced anchorage-independent growth lose their mitogenic response to EGF.

Screening for alcoholism: techniques and issues.

Alcoholism is an often overlooked health problem because alcoholics usually do not seek treatment for their drinking problems. They do, however, seek general medical care for other health reasons, and a number of screening techniques have proven useful for identifying alcoholics. The advantages and disadvantages of self-report, as well as biochemical techniques that have been found effective in screening for alcoholism, are discussed. We recommend that future research be aimed at developing quick, accurate, and inexpensive screening devices that also can evaluate the severity of the alcohol problem. Ideally, screening procedures would discourage feigned responses, differentiate between drinking and consequences of drinking, and permit the identification of subtypes of alcoholics. Better understanding of the types of errors made by common screening instruments would enable researchers to construct an optimal sequencing strategy for screening for alcoholism.

Alcoholism treatment service systems: a health services research perspective.

This article examines the role of health services research in alcoholism treatment. Alcoholism services research has only recently emerged as a self-defined discipline. Alcoholism services research can be grouped into five classifications: a) descriptive studies of resources for alcoholism treatment and of the use or cost of these services, b) estimates of the need or demand for alcohol services in the population or in particular subpopulations, c) studies of the costs or cost-effectiveness of alcoholism treatment or of alternative treatments, d) studies of the possible "cost-offsets" of treating alcoholism, and e) studies that examine strategies for financing and reimbursement for alcoholism treatment. Research is needed to determine how alcoholism treatment services are now delivered, who uses these services, how treatment setting and organization affect service delivery, who pays for alcoholism treatment, and how reimbursement policies affect the delivery of alcoholism services. Research on large-scale social issues is also needed, such as the effects of warning labels appearing on alcoholic beverage containers or estimates of the overall cost to society of alcohol abuse.

Care of children with psychiatric disorders at community hospitals.

Short-term general hospitals account for most psychiatric hospitalizations of children, but relatively little research has examined the psychiatric care of children at these facilities. This study compared the characteristics of and use of hospital services by children and adults who received a primary psychiatric diagnosis at 380 short-term general hospitals in 1977. Of the 100,000 patients studied, 7,000, or 7 percent, were children, most between the ages of 12 and 17. Children 12 and older were hospitalized the longest, a mean of 15.6 days, followed by adults (12.7 days), children between six and 11 (10.7 days), and children five and younger (5.6 days). The great majority of children under age 12 and roughly one-third of children between ages 12 and 17 were not seen by a psychiatrist during their hospital stay. Very few were seen by child psychiatrists. The authors believe that child psychiatrists should be concerned about the effect their relative absence from general hospitals has on quality of care.

Factors associated with the use of psychiatric consultations in short-term general hospitals.

A significant number of patients in general hospitals suffer from psychiatric distress or illness, but not all receive psychiatric consultation. This study examined several potential predictors of such consultation. These included patient characteristics (age, sex, race, insurance, disease stage, and number of medical diagnoses), characteristics of hospital stay (number of procedures, other consultations, length of stay, discharge destination), hospital characteristics (size, percent occupancy, teaching status, presence of a psychiatric unit, type of control), and community characteristics (region, urban/rural setting). Data were derived from a national sample of 327 hospitals. Parallel analyses using stepwise logistic regression were carried out across four samples: patients determined at discharge to have been hospitalized for diabetes, hip fracture, chronic obstructive pulmonary disease, and coronary artery bypass surgery. Results show a wide variation in the use of psychiatric consultations across different subgroups. Longer lengths of stay, urban setting. Northeast region, younger patient age, and other consultations were the most consistent predictors of the probability of psychiatric consultation. These variations may reflect differences in the need for consultation, differential recognition of these needs by providers, or differential availability of psychiatric consultation services. Moreover, they may have implications for equity and/or quality of hospital care.

Psychiatric consultations in short-term general hospitals.

We investigated the use of psychiatric consultations in short-term general hospitals using a national sample of 327 hospitals and examining the hospital experience of approximately 263,000 patients discharged from these hospitals. We found that the demographic characteristics of patients receiving psychiatric consultations in the national sample were roughly similar to those reported for patients receiving consultations in earlier, single-hospital studies. Rates of consultation were considerably lower, however: 0.9%, compared with a median rate of 3.3% reported in the literature. We also found that patients receiving psychiatric consultations used more hospital resources than other patients.

Male-female differences in mental health visits under cost-sharing.

This article, which was prepared as part of a larger study of the impact of the copayment requirement on United Mine Workers of America (UMWA) beneficiaries carried out at the National Center for Health Services Research (NCHSR), compares male to female changes in ambulatory care visits for mental disorders and discusses the implications of these changes for the use of other services and for the quality of care. Figures were derived from aggregate claims data provided by the UMWA for the time periods immediately preceding the introduction of copayment (full coverage for all health care) and the first year following the introduction of copayment. Our findings suggest that, at least as far as visits for mental disorders are concerned, copayment may reduce necessary visits. The men in our population, who sought care for mental disorders more sparingly than women and for more severe complaints, were most affected by copayment.

Assessment of plasmid profile, exoenzyme activity, and virulence in recent human isolates of Yersinia enterocolitica.

We examined a group of 23 recent clinical isolates of Yersinia enterocolitica recovered from symptomatic patients residing in the New York, N.Y. area. These isolates were tested for the presence of plasmids, exoenzyme activity, mouse lethality, and phenotypic properties postulated to correlate with virulence. Of the 23 isolates, 17 harbored a 60- to 65-kilobase (kb) plasmid. Six isolates were lethal for white mice, showed the phenotypic markers of autoagglutination and calcium dependence for growth at 37 degrees C, and contained a 60- to 65-kb plasmid. Restriction endonuclease analysis with several different enzymes revealed the presence of three distinct plasmid profiles in these isolates. Isolates with a single plasmid of 60 to 70 kb, typical for this species, were detected, but these were of three distinct types as judged from restriction enzyme digestion. One strain was unusual among clinical isolates of Y. enterocolitica in that it contained at least four distinct plasmids. In addition, this nontypable strain showed exoenzymatic activity similar to that of serogroup O8 isolates, was not lethal to mice, and did not require calcium for growth at 37 degrees C.