Prenatal diagnosis in diabetic gravidas: utility of ultrasound and maternal serum alpha-fetoprotein screening.

The differences in both the biology of pregnancy and the content of routine care between gravidas with and without diabetes mellitus lead to important differences in the potential utility of both ultrasound examination and maternal serum alpha-fetoprotein (MSAFP) screening. However, both diagnostic methods have become standards of care for these patients, without critical evaluation. This study examines the utility of both ultrasound and MSAFP in diabetic women. Four hundred thirty-two women with diabetes mellitus antedating pregnancy were examined sonographically between 12-23 weeks' gestation. Of these, 393 were also screened with MSAFP determinations. At delivery, 32 of these fetuses were found to have 38 major congenital malformations. All fatal or potentially life-threatening defects had been diagnosed in utero by sonography before 24 weeks' gestation. Ultrasound had a positive predictive value of 90% and a negative predictive value of 97% for identification of major birth defects before 24 weeks' gestation. There were 14 MSAFP values greater than 2.0 multiples of the median, and nine of these patients elected to undergo amniocentesis. Maternal serum alpha-fetoprotein screening had a positive predictive value of 17% and a negative predictive value of 94%. No malformations were detected through MSAFP screening that had not been diagnosed by sonography. No malformations missed sonographically were detected by MSAFP screening, and none of the amniocenteses were helpful diagnostically. We conclude that MSAFP screening is of minimal utility for diagnosing major congenital malformations in a high-risk population examined universally by an experienced sonographer.     

Self-inflicted orbital and intracranial injury with a retained foreign body, associated with psychotic depression: Case report and review

Reports of intracranial self-multilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed.     

Clinical and laboratory observations in a lymphoma-prone family

Three sisters developed non-Hodgkin's lymphoma (NHL). Thirteen maternal relatives had adenocarcinomas of various types, predominantly breast and large bowel. Detailed laboratory assessment of this family revealed a variety of immunologic abnormalities. Two lymphoma patients had elevated anti-early antigens (EA) Epstein-Barr virus (EBV) titers. One of the two also had a markedly elevated anti-viral capsid antigen (VCA) EBV titer. The two lymphoma patients were human leukocyte antigen (HLA)-identical, but two unaffected siblings shared the same HLA haplotypes. One of the lymphoma patients and four unaffected family members were anergic; and three unaffected family members had a decreased percentage of T-cells. These data suggest that a subtle disturbance in cellular immune functions may play a causal role in some familial aggregations of malignant lymphoma.     

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.     

"Single-exposure" dual energy digital radiography in the detection of pulmonary nodules and calcifications

We studied the detectability of mineralized and non-mineralized simulated pulmonary nodules with dual energy digital radiography. "Soft tissue" and "bone" images (pixel size = 0.2 mm, 10 bits deep) were obtained with subtraction image processing after a single simultaneous exposure (100 kVp, 8 mAs, 17 mR skin exposure dose) of two storage phosphors with an interleaved 0.9 mm copper wafer. Three classes of paraffin-based nodules (0.5 to 3.0 cm) of varying mineral concentration (0, 120 and 190 mg/cm3 K2HPO4) were randomly positioned on the chest wall of two healthy volunteers to simulate calcified and non-calcified nodules. The average receiver operating characteristics (ROC) area of six readers (n = 2880 observations) showed that digital "bone" images (ROC area: 0.77 +/- 0.03) were significantly better (P less than 0.04) than conventional radiographs (OC Film, Lanex medium screens, 141 kVp, 19 mR skin exposure dose) (ROC area: 0.71 +/- 0.05) in detecting calcification in nodules. The unsubtracted digital images of lower kilovoltage were not superior to the 141 kVp conventional radiographs in a subgroup of two readers (ROC area: 0.73 +/- 0.02). Digital "soft tissue" images were equivalent to conventional chest radiographs in detecting soft tissue pulmonary nodules (ROC areas: 0.92 +/- 0.04 and 0.92 +/- 0.05, respectively.     

A comparative isokinetic evaluation of a functional ankle orthosis on talocalcaneal function

The purpose of this study was to determine the effectiveness of a semirigid orthosis in restricting ankle inversion-eversion range of motion (ROM), and evaluate its effect on subjects' ability to produce muscular torque, during pre- and post-exercise test conditions. Thirty healthy subjects, 15 males and 15 females, with no history of right ankle injury were evaluated. Active ankle inversion-eversion torque and angular displacement were measured on a LIDO(R) isokinetic system, with the subjects' right ankle positioned in 0 degrees of plantarflexion. T-tests for paired samples at the 0.001 confidence level revealed that the orthosis demonstrated significant inversion-eversion range restrictive capabilities; did not interfere with maximum inversion-eversion torque production; and retained its support effectiveness following 20 minutes of dynamic exercise. The results suggest that the tested orthosis may be an effective prophylactic in preventing ankle sprains and beneficial to individuals with chronic ligamentous instability. J Orthop Sports Phys Ther 1989;11(6):245-252.     

BRCA1 and sex ratio

Two recent papers suggest distorted sex and transmission ratios associated with BRCA1 mutations. If real, these would provide novel insights into the normal biological function of this gene and have implications for genetic epidemiologic methods used to estimate penetrance. We addressed these observations in two settings: offspring of 283 mutation carriers and 471 mutation negative subjects from BRCA1/2 mutation-positive families with multiple cases of breast and ovarian cancer (NCI families); and relatives of 115 BRCA1/2 mutation carriers from the Washington Ashkenazi Study (WAS). The male:female ratio was below one in both BRCA1 (0.85, 95% CI 0.7-1.1 in NCI families; 0.90, 95% CI 0.6-1.4 in WAS) and BRCA2 families (0.77, 95% CI 0.5-1.3 and 0.80, 95% CI 0.5-1.2, in the NCI and WAS study groups, respectively). None of the sex ratios deviated significantly from one, and there was no significant difference between BRCA1 and BRCA2 families. The reduced sex ratio was due largely to the offspring of males, a distortion that is probably an artifact of ascertainment biases. Among adult daughters without breast or ovarian cancer born to mutation carriers, as expected, fewer than 50% were mutation carriers (39% in BRCA1 families and 44% in BRCA2 families). It is difficult, due to ascertainment biases, to draw firm conclusions regarding sex ratios in studies of a sex-limited phenotype. Nonetheless, these observations do not support the idea that BRCA1 mutation carriers have a lower ratio of male offspring than BRCA2 mutation carriers.     

Impaired Microvascular Function in Normal Children: Effects of Adiposity and Poor Glucose Handling

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat ( r =−0.20, P < 0.05 and r =−0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l⁻¹) showed significantly lower vasodilatation to both ACh (   P < 0.005  ) and SNP (   P < 0.02  ) than those in the lower quintile (range 3.9-4.9 mmol l⁻¹). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile ( P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin ( r = 0.59, P < 0.001) and with the fasting insulin resistance index ( r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated ( r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.