AUTOPSY FINDINGS IN THE WOLCOTT-RALLISON SYNDROME

Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by diabetes mellitus arising in early infancy and multiple epiphyseal dysplasia. To date, nine cases have been described in the world literature. We report an affected girl who died at the age of 4 years and on whom a full autopsy was performed. In addition to neonatal diabetes mellitus and epiphyseal dysplasia, this child had mental retardation and recurrent episodes of self-limiting hepatic failure. Autopsy revealed severe pancreatic hypoplasia and markedly abnormal pancreatic histology, while histology of the bone was consistent with epiphyseal dysplasia. There was laryngeal stenosis and pulmonary hypoplasia. The heart was enlarged with mitral valve dysplasia and stenosis, left atrial dilatation, left ventricular hypertrophy, and endocardial fibroelastosis. Examination of the central nervous system showed arrhinencephaly and cerebellar cortical dysplasia. The liver showed minor histological abnormalities but no features were present to account for the recurrent hepatic failure. In addition to Wolcott-Rallison syndrome this child had a deletion at 15q11-12 in 65 of her cells.     

Evaluation of sexual misconduct complaints: The Oregon Board of Medical Examiners, 1991 to 1995

OBJECTIVE: In 1991 the Oregon Board of Medical Examiners initiated a separate category for the complaint of sexual misconduct. Investigated complaints of sexual misconduct brought to the Oregon Board of Medical Examiners were analyzed for the years 1991 to 1995 to serve as a baseline. Comparison was made to the Federation of State Medical Boards sexual misconduct data for 1991 and 1992.STUDY DESIGN: One hundred complaints brought against 80 licensees were evaluated by practitioner's degree, age group, sex, specialty, and disposition of complaints for the years 1991 to 1995. The allegations were classified into behavior categories of sexual impropriety, sexual transgression, and sexual violations.RESULTS: Sexual misconduct was the allegation in 5.9% of the complaints investigated for the study period. Oregon had more sexual misconduct complaints than the average reported to the Federation of State Medical Boards for the years 1991 and 1992. Most (72%) complaints came from the patients or their families. Two female physicians (2.4%) had sexual boundary complaints. Sexual misconduct complaints increased by a risk ratio of 1.44 with advancing age by decades. Allegations classified into behavior categories according to severity revealed 39% sexual impropriety, 31% sexual transgression, and 30% sexual violation. Reportable disciplinary actions occurred only with multiple allegations of sexual impropriety (6.5%) and for sexual transgression (27%) whereas sexual violation allegations often had one complainant but there were 54% reportable disciplinary actions. Family practice, obstetrics and gynecology, and psychiatry had the highest incidence of sexual misconduct complaints whereas psychiatry and obstetrics and gynecology had the highest incidence of reportable disciplinary actions. Twenty-five percent of the closed cases resulted in reportable disciplinary actions. This analysis is discussed in relationship to legal and ethical issues and the goal of zero tolerance.CONCLUSIONS: Oregon has a higher percentage of sexual misconduct complaints than the average for 42 states reporting to the Federation of State Medical Boards for the years 1991 and 1992. Analysis of the Oregon Board's experience for the study years will provide a baseline for future evaluation and as an educational resource for the Oregon Board of Medical Examiners and professional and specialty societies. Ethical standards, the reporting and investigative processes, and the legal framework are in place and lessen the incidence of sexual misconduct and work toward zero tolerance. (Am J Obstet Gynecol 1997;176:1340-8.)     

Urinary stability of carboxycyclophosphamide and carboxyifosfamide, two major metabolites of the anticancer drugs cyclophosphamide and ifosfamide

Phosphorus-31 nuclear magnetic resonance spectroscopy was used to evaluate the stability of carboxycyclophosphamide (CXCP) and carboxyifosfamide (CXIF) in human urine at pH 7.0 and 5.5 at 25°, 8°, −20°, and −80 °C. At 25 °C and pH 7.0, CXCP and CXIF are relatively stable (≈10% degradation in 24 h). In contrast, they are much less stable at pH 5.5 (≈80% degradation of CXIF and ≈50% degradation of CXCP in 24 h). The rate of degradation of CXCP and CXIF was a function of the storage temperature of the urine samples but, even at −80 °C, was not negligible: ≈30% degradation for CXCP irrespective of pH and ≈40% and 50% degradation for CXIF at pH 7.0 and 5.5, respectively, after storage for 6 months. CXCP was more stable than CXIF at either pH (7.0 or 5.5) and at all storage temperatures (8°, −20°, or −80 °C) of the urine samples. CXCP and CXIF were more stable at pH 7.0 than at pH 5.5, although this difference fell with decreasing temperatures to be almost negligible at −80 °C. To ensure a true estimate of CXCP and CXIF levels, urine samples must be frozen and stored at −80 °C within a few hours of micturition. CXCP and CXIF assays should also be carried out within 2 months and 1 month of storage, respectively. Received: 13 July 1996 / Accepted: 20 January 1997     

Routine Physical Examination and Forgone Health Care among Latino Adolescent Immigrants in the United States

Knowledge concerning patterns of health care utilization among Latino-adolescent immigrants is needed to develop culturally-appropriate programs. The objectives of this study were to estimate the annual prevalence of having had a routine physical exam and episodes of adolescents’ not seeking health care when they thought they should (forgone health care) among Latino adolescents by immigrant-generational status. Cross-sectional analysis of data from Latino adolescents in Wave I of the National Longitudinal Adolescent Health Study. First-generation immigrants who had lived in the U.S. ≤ 5 years were less likely to receive routine care than third-generation immigrants (39.0% vs. 54.9%). This disparity decreased after adjustment for insurance status, parental education and poverty among Mexican origin adolescents. On average, 16.0% of first-generation immigrants who had lived in the U.S. ≤ 5 years and 22.5% of third-generation immigrants reported forgoing health care. After adjustment for age, insurance status, parental education and routine care, recent arrivals were less likely than third-generation immigrants to forgo health care. Recent arrivals were less likely to receive a routine physical exam and to forgo care than third-generation immigrants. Future studies should explore the effect of acculturation on knowledge, beliefs and perceptions about health, illness and care-seeking behaviors.     

Perforation of the bowel from intrauterine contraceptive devices: case series and discussion

The intrauterine contraceptive device is used extensively in the female population. Serious complications are rare, but they do occur. We discuss three cases of bowel perforation caused by these devices following their perforation through the uterine wall. It is important that cases of perforation be recognised swiftly and the possibility of involvement of other organs considered.     

Resistance to the tubulin-binding agents in renal cell carcinoma: no mutations in the class I beta-tubulin gene but changes in tubulin isotype protein expression.

PURPOSE: The primary purpose of this study was to determine whether mutations of the class I beta-tubulin gene may be implicated in the inherent resistance to tubulin-binding agents (TBA) in renal cancer, with a small number of samples and cell lines also being examined for class I and III beta-tubulin isotype protein expression. EXPERIMENTAL DESIGN: DNA was extracted from 90 renal tumors and the class I beta-tubulin gene analyzed for mutations. For each sample, eight PCRs were used to cover the complete coding sequence with intronic primers ensuring highly homologous pseudogenes were not coamplified. Additionally, expression levels of class I and III beta-tubulin isotypes in 17 matched normal and malignant renal samples and a panel of renal cell carcinoma cell lines with differing intrinsic resistance to the TBAs was examined by Western blotting. RESULTS: Four polymorphic sequence changes of the class I beta-tubulin gene were identified with no mutations. Class I protein expression levels were higher in tumor tissue versus normal tissue, whereas class III expression showed no consistent change. In renal cancer cell lines, a significant correlation between class III isotype expression and vinblastine sensitivity was observed. CONCLUSIONS: These results do not support a role for mutations in the class I beta-tubulin gene in the intrinsic resistance of renal cancer to TBAs. Class III isotype expression may be implicated in resistance in vitro but in vivo, changes in class I isotype expression in renal cell carcinoma tissue may support a role in resistance to the TBAs and warrants further investigation.     

Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.