Diagnosis and management of fetal ductus arteriosus constriction-closure.

Pathognomonic features of in utero premature restriction/closure of the ductus arteriosus (DA) are increased right ventricular afterload, impaired right ventricular function, and consequently tricuspid regurgitation and right heart dilation. The most common reason for constriction-closure of DA is maternal administration of non-steroidal anti-inflammatory drugs (NSAIDs) during the 3rd trimester of gestation. The idiopathic form is a rare event and, maybe, an underestimated abnormality that, if it is not promptly recognized, may result in severe fetal-neonatal compromise. We describe a case of a 38-year-old woman presenting at 34+0 weeks of gestation with a normally grown male fetus whose fetal echocardiography had shown right ventricular hypertrophy, a tortuous S-shaped DA and a significant pulmonary hyperflow. All signs were consistent of an idiopathic severe constriction of DA with a significant fetal cardiac involvement. The patient was admitted to a tertiary care center equipped with Neonatal Intensive Care Unit (NICU), and delivered by cesarean section at 34+4 weeks with a good maternal and neonatal outcome. Based on our experience and a review of the Literature we propose a management algorithm to use when dealing with preterm or early term pregnancy complicated by this fetal hemodynamic malfunction.

Anatomy reports on the internet: a web-based tool for student reports on cadaveric findings.

The difference between the idealization of anatomy atlases and the reality of human cadavers often frustrates gross anatomy students. To encourage students to celebrate rather than protest these differences, we describe a web site ARI (Anatomy Reports on the Internet) that allows students to document cadaveric findings online with photographs and text. We used several web languages for site construction, including mysql, php, html, and javascript. Faculty tools allow instructors to upload digital images of the structures, add relevant commentary, view and delete images, review submitted reports, and examine database statistics. Student tools allow dissection groups to choose and comment on images, enter and edit reports, and read reports submitted by other students. During the first two years of the site's use (2000-2001, 2002-2003), every dissection group at our institution submitted at least one report. Technical support requests were minimal.

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants.

BACKGROUND: To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12-15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. RESULTS: Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever >or=38.0 degrees C following each vaccination was reported more frequently in the PCV7 group (28.3-50.0%) than in the Control group (15.6-33.6%) whereas fever >39.0 degrees C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8-2.7%; Control, 1.6-4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. CONCLUSION: DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12-15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children.

Controlling invasive pneumococcal disease: is vaccination of at-risk groups sufficient?

Risk factors for invasive pneumococcal disease (IPD) include young and old age, comorbidities (such as splenic dysfunction, immunodeficiencies, chronic renal disease, chronic heart or lung disease or cerebral spinal fluid leak), crowded environments or poor socioeconomic conditions. Universal use of the 7-valent pneumococcal conjugate (7vPncCRM) vaccine for infants and young children has led to significant decreases in IPD in the vaccinated population (direct protection), and there has also been a decrease in the incidence of IPD among the nonvaccinated population (indirect immunity; herd protection). While 7vPncCRM vaccine is administered universally to children in USA, many countries of the European Union have chosen to target children with comorbidities. This review aims to highlight individual risk factors for IPD, describe studies that evaluated pneumococcal conjugate vaccines in at-risk groups and estimate the proportion of at-risk children who may have been vaccinated in the European Union since the 7vPncCRM vaccine was introduced, using UK as an example. Although immunisation targeting only children with comorbidities may achieve satisfactory results for a few, many otherwise healthy children at risk simply because of their age will be neglected, and herd protection might not be established.

Heart failure in Parkinson's disease: analysis of the United States medicare current beneficiary survey.

OBJECTIVE: We sought to examine the prevalence of heart failure in elderly PD versus non-PD patients using a national sample of Medicare beneficiaries in the United States. SCOPE: The prevalence of heart failure in elderly PD patients was 2.27 times that of non-PD patients (19.4% versus 8.7%, 95% CI = 1.43-3.60, p 0.0005), and remained twice as high after excluding patients with stroke and possible vascular parkinsonism. CONCLUSIONS: In this cross-sectional study of a national Medicare database, heart failure occurred twice as frequently in elderly PD patients as in non-PD patients. Prospective studies are warranted to verify these findings.

Driving safety in Parkinson's disease.

In this study, 39 patients with PD and 25 control subjects without neurologic disease completed testing in a driving simulator. PD patients had more total collisions on the driving simulator than control subjects (t = -3.7, p < 0.01). In PD patients, collisions were associated with Hoehn and Yahr stage (chi(2) = 12.4, p = 0.006) and correlated with Unified Parkinson's Disease Rating Scale score (r = 0.5, p < 0.01).

Bilateral human fetal striatal transplantation in Huntington's disease.

BACKGROUND: Transplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington's disease (HD). OBJECTIVE: To evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD. METHODS: Seven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months. RESULTS: Three subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 plus minus 6.2 at baseline and 29.7 plus minus 7.5 12 months after surgery (p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 plus minus 6.2 at baseline and 27.5 plus minus 5.2 at 12 months (p = 0.03). CONCLUSIONS: Transplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.

Computerized weight loss intervention optimizes staff time: the clinical and cost results of a controlled clinical trial conducted in a managed care setting.

OBJECTIVE: To evaluate the costs and effects of incremental components of a weight-loss program. DESIGN: A 3-arm, 12-month randomized controlled clinical trial to evaluate 3 incremental levels of intervention intensity. SUBJECTS/SETTING: The study included 588 individuals (BMI > 25 kg/m2) in a freestanding health maintenance organizalion and achieved an 81% completion rate. INTERVENTION: Using a cognitive behavioral approach for tailoring lifestyle modification goals, the incremental levels of intervention included a) a workbook alone, b) the addition of computerized tailoring using onsite computer kiosks with touch screen monitors, and c) the addition of both computers and staff consultation. MAIN OUTCOME MEASURES: Endpoints included weight parameters, lipid profile, plasma glucose, blood pressure, intervention costs, dietary intake, and physical activity. STATISTICAL ANALYSIS PERFORMED: Study endpoints were analyzed using analysis of variance for normally distributed variables and analysis of covariance to control for any baseline differences. Regression and correlation analysis assessed the relationship between weight loss and other variables. RESULTS: For the increasing levels of intervention intensity, the mean 12-month weight losses were 2.2, 4.7, and 7.4 pounds, with the respective cost per participant being $12.33, $41.99, and $133.74. The decreases in mean BMIs for these respective intervelation levels were 0.4, 0.9 and 1.2. All groups reported a decrease in energy and fat intake and an increase in blocks walked (P<.01). Intervention variables that correlated with weight loss included more computer log-ons, achieving computer-selected goals, more self-monitoring, increased walking, and decreased energy and fat intake, as well as higher attendance in staff consultation group sessions for that treatment condition. Weight loss correlated with decreases in fasting glucose and blood pressure. APPLICATIONS/CONCLUSIONS: In a weight-loss program, computers can facilitate selecting behavioral change goals. More frequent usage resulted in greater weight loss. Staff counseling to augment the computer intervention achieved the most weight loss.

MMPI-2 fake-bad scales: an attempted cross-validation of proposed cutting scores for outpatients.

Minnesota Multiphasic Personality Inventory-2 (MMPI-2) results were compared in 118 psychiatric outpatients given standard instructions, instructions to exaggerate their problems, instructions to feign a disorder they did not have, or instructions to feign global psychological disturbance. The groups were comparable on demographic, occupational and diagnostic characteristics as well as intake MMPI-2 results. Experimental MMPI-2 results showed that clinical scales were generally elevated in the feigning groups, with only modest differences across dissimulating instruction sets. The feigning groups had reliably higher scores than controls on all overreporting indexes examined, although no significant differences between feigning groups were present for overreporting indexes. Classification rates using previously proposed cutting scores for outpatients on individual feigning indexes showed near perfect specificity, but low to at best moderate sensitivity. Multiple regression analyses indicated that Gough's (1954) Dissimulation Scale (Ds2) was most strongly related to feigning status, and no other feigning scale contributed a significant increment in predictive power once Ds2 was entered.

Estimating software development costs for a patient multimedia education project.

The authors compare alternative methods of cost estimation for a patient multimedia education (PME) program, using a computerized weight-reduction PME project as an example. Data from the project planning and budgeting process and actual costs of the completed project are analyzed retrospectively to calculate three different estimates-pre-work, post-work, and actual work. Three traditional methods of estimating the cost of computer programs (the lines-of-code, function point, and task ratio analyses) underestimate costs in this example. A commercial program (Cost Xpert) that calculates the cost of developing a graphical user interface provided a better estimate, as did a tally reflecting the complexity and quality of media material in the project.

Purification and characterization of a new plant endopeptidase isolated from latex of Asclepias fruticosa L. (Asclepiadaceae).

Asclepias fruticosa L. is a small shrub containing latex with proteolytic activity. The crude extract (latex diluted 1:250 and ultracentrifuged) contained 276 microg of protein/mL and the proteolytic activity reached 1.2 caseinolytic U/mL. This enzyme preparation was very stable even after 2 hours at 45 degrees C, but was quickly inactivated after 5 minutes at 80 degrees C. Chromatographic purification was achieved by FPLC using a cation exchanger (SP-Sepharose FF). Thus, a unique proteolitically active fraction could be isolated, being homogeneous by bidimensional electrophoresis and mass spectrometry (Mr = 23,652). The optimum pH range was achieved at 8.5-10.5. The enzyme activity was completely inhibited by specific cysteine peptidases inhibitors. Isoelectric focusing followed by zymogram showed the enzyme had a pI greater than 9.3. The N-terminus sequence (LPDSVDWREKGVVFPIRNQGK) shows a great deal of similarity to those of the other cysteine endopeptidases isolated from latices of Asclepiadaceae even when a high degree of homology could be observed with other plant cysteine endopeptidases.

Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein.

Consumption of soybean-rich diets is thought to provide significant health benefits such as prevention of cancer, primarily because of the high contents of factors such as the isoflavones genistein and daidzein. Isoflavones circulate and are excreted into the urine mainly as glucuronide and sulfate conjugates. This study was conducted to determine the urinary pharmacokinetics of sulfate and glucuronide conjugates of genistein and daidzein. Twelve volunteers consumed a soy beverage providing 1 and 0.6 mg/kg body weight of genistein and daidzein equivalents, respectively. Urine was collected at various times during the 48 h after soy consumption and was digested with either glucuronidase or sulfatase, and the liberated aglycones were extracted and analyzed by liquid chromatography-mass spectrometry. Urinary isoflavone sulfate levels were determined by two methods: (a) assessment of aglycone after sulfatase hydrolysis (measured); or (b) calculated by subtracting the aglycone + glucuronide levels from the total urinary isoflavone levels. The apparent terminal half-life for daidzein sulfate (3.9+/-0.5 h) that was determined from sulfatase-treated urine was 32% shorter (P < or = 0.02) than that of the calculated daidzein sulfate (5.7+/-0.08 h). A similar trend was obtained for genistein sulfate (4.5+/-0.7 versus 6.8+/-0.1 h). The apparent terminal half-lives for genistein and daidzein glucuronides were 6.0+/-0.4 and 3.8+/-0.4 h, respectively. These data suggest that the measured urinary isoflavone sulfate values provide a better understanding of the pharmacokinetics than the calculated values. Additional studies are needed to determine whether the apparent terminal half-lives can be attributed to elimination or absorption processes.

Bringing a virtual library to a small group classroom.

A small group case discussion class would seem to be the ideal setting for a virtual library. Two courses at the Albert Einstein College of Medicine were observed. One hour of observation was of groups with no computer available, one hour of groups with a computer available "incidentally", and two hours of groups with computer integrated case material. Across all groups, at least one student was using a reference source (paper or computer) 55% of the time. In a room with no computer, paper references were used 59% of the time. In a room with a computer, references were used 53% of the time (18% computer only, 13% paper only, 22% both). While the amount of data is insufficient for detecting statistically significant difference, this study does provide important baseline data not previously available concerning reference use behavior for electronic and paper sources.

An LC-MS method to determine concentrations of isoflavones and their sulfate and glucuronide conjugates in urine.

Most methods for detecting isoflavones in biological samples do not measure the concentration of sulfate conjugates. An LC-MS method is reported here to estimate urinary concentrations of genistein and daidzein, their sulfate and glucuronide conjugates and other major metabolites. Human and rat urine samples were extracted with diethyl ether, or pre-digested with sulfatase and/or beta-glucuronidase followed by extraction. The isoflavones were separated using gradient LC methods and detected by negative single ion monitoring on an MS system using a heated nebulizer atmospheric pressure chemical ionization interface. CVs for inter- and intra-assay variability were generally < 20 and 10%, respectively. Preliminary studies using these procedures demonstrate 52+/-4 and 26+/-4% of genistein in rat urine was found as the aglycone and sulfate conjugates, respectively, compared to 0.36 and 4%, respectively, in human urine. This method is suitable for the study of isoflavone sulfate conjugates in biological fluids.

Arterial supply of limbic structures in the guinea pig.

This study outlines the vascular territories of the cerebral arteries that originate from the Willis circle to supply limbic structures in the guinea pig brain. The entire cerebral vascular system was visualized in four preliminary experiments by performing superselective microangiographic studies with iodine contrast medium perfusion of the whole brain after in vitro isolation according to a technique described previously (de Curtis et al. [1991] Hippocampus 1:341-354). Subsequently, the perfusion territory of the different arteries that originate from the Willis circle was characterized after cannulation and perfusion of individual arteries with a gelatin solution that contained waterproof black ink. The analysis was performed by identifying the brain regions that contained the black stain on 150-microm-thick coronal sections that were cut after brain fixation with paraformaldehyde for at least 1 week. The middle cerebral artery and the rostral and caudal posterior cerebral arteries supply the limbic cortices and some related subcortical regions. In particular, large portions of the hippocampal formation are supplied by both the rostral posterior cerebral artery and the rostral branch of the caudal posterior cerebral artery, whereas the ventral temporal part of the hippocampus is served exclusively by the rostral posterior cerebral artery. The amygdala, the periamygdaloid cortex, and the piriform cortex are served by the middle cerebral artery and in part by the perforating arteries. The entorhinal, perirhinal, and postrhinal cortices are vascularized by the posterior and middle cerebral arteries, with a very broad overlap between the distal territories of these vessels. The demonstration of an extensive superimposition between the arterial supply of the entorhinal and the perirhinal regions suggests the presence of anastomotic connections that potentially are protective against ischemic events. Such an arrangement was not observed for the arteries that supply the ventral portion of the hippocampal formation and the basolateral amygdala, which showed nonoverlapping boundaries. The pathophysiological consequences of a similar vascular organization are discussed.

The dependence of educational infrastructure on clinical infrastructure.

The Albert Einstein College of Medicine needed to assess the growth of its infrastructure for educational computing as a first step to determining if student needs were being met. Included in computing infrastructure are space, equipment, software, and computing services. The infrastructure was assessed by reviewing purchasing and support logs for a six year period from 1992 to 1998. This included equipment, software, and e-mail accounts provided to students and to faculty for educational purposes. Student space has grown at a constant rate (averaging 14% increase each year respectively). Student equipment on campus has grown by a constant amount each year (average 8.3 computers each year). Student infrastructure off campus and educational support of faculty has not kept pace. It has either declined or remained level over the six year period. The availability of electronic mail clearly demonstrates this with accounts being used by 99% of students, 78% of Basic Science Course Leaders, 38% of Clerkship Directors, 18% of Clerkship Site Directors, and 8% of Clinical Elective Directors. The collection of the initial descriptive infrastructure data has revealed problems that may generalize to other medical schools. The discrepancy between infrastructure available to students and faculty on campus and students and faculty off campus creates a setting where students perceive a paradoxical declining support for computer use as they progress through medical school. While clinical infrastructure may be growing, it is at the expense of educational infrastructure at affiliate hospitals.