Selecting a physical medicine and rehabilitation residency.

A 35-item questionnaire, designed to assess the relative importance of various factors to medical students when ranking physical medicine and rehabilitation (PM&R) residency training programs during the Match, was sent to all members of the 1991 senior class after Match Day. This mailing was coordinated with the National Resident Matching Program. The questionnaire was also sent to all PM&R residency training program directors and all physiatrist faculty members at the University of Medicine and Dentistry of New Jersey--New Jersey Medical School (UMDNJ-NJMS). Recipients were asked to grade selection factors based on a numerical scale: 1, extremely important; 2, very important; 3, important; 4, minimally important; 5, not important. A response rate of 41% (73/179) for medical students, 87% (62/71) for residency training directors and 71% (22/31) for UMDNJ-NJMS faculty members was attained. Analysis of the results indicates that, overall, there is no significant difference in ranking of the factors by each of the three groups surveyed. The intergroup responses for one-third of the factors were significantly different. Diversity of the training experience, current house officer satisfaction, it "feels" right and house officer quality were the four most important selection factors to the medical students.     

Brain stem auditory evoked response—A study in parameters

Brain stem audiory evoked response (BAER) audiometry is a non-invasive and objective measure of a subject’s auditory function. The present paper attempts to establish normative data in Indian subjects. It was found that the BAER can detect asymptomatic high frequency hearing losses. Wave V’s threshold, latency and amplitude, along with comparisons between the auditory (subjective) and BAER threshold, are useful parameters in testing for organic and non-organic hearing disorders.     

Profuse variceal hemorrhage as a presenting feature of pancreatic adenocarcinoma in a young non-icteric patient

Pancreatic adenocarcinoma can present with a vast spectrum of rare manifestations. It usually occurs after the age of 50 years, the peak incidence being in sixth and seventh decades. We report a previously asymptomatic subject of pancreatic adenocarcinoma who presented for the first time with massive upper gastrointestinal hemorrhage. Endoscopy revealed ruptured esophageal varices which were secondary to tumour-induced thrombosis of the portal vein. Besides the uncommon mode of presentation, the patient was unusual because of his young age. Further, he was non-icteric at the time of presentation and remained so throughout the clinical course despite having a large lesion in the head of the pancreas.     

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.     

Assessment of the epidemic potential of a new strain of rotavirus associated with the novel G9 serotype which caused an outbreak in the United States for the first time in the 1995-1996 season

Rotavirus causes severe morbidity in developed countries and frequent deaths (> or = 500,000 per year) in less-developed countries. Historically, four serotypes--G1, G2, G3, and G4-have predominated; they are distinguished by one of two surface neutralization antigens (VP7). However, in 1983 and 1984 we described a new rotavirus serotype, designated G9, in five children hospitalized for diarrhea in Philadelphia, Pa. G9 rotavirus was not identified again in the Western Hemisphere until it caused ca. 50% of the rotavirus disease detected in Philadelphia in the 1995-1996 season. This outbreak allowed us to question whether a rotavirus strain completely new to a well-studied community would target either very young infants or older children, cause especially severe disease, or completely displace previously extant serotypes. We observed a significant excess of G9 infections in younger infants (especially in those < 6 months old) that might be attributed to the lack of G9-specific antibodies in mothers. Of further note, six of the seven oldest patients with rotavirus diarrhea were infected with the G9 strains (not significant). However, the age distribution of children with rotavirus did not differ over a 5-year study period regardless of the infecting serotype. Patients with diarrhea associated with G9 strains did not have disease more severe than that caused by the G1, G2, or G3 serotype. G9 strains did not displace the other serotypes but were virtually completely replaced by G1 or G2 serotypes in the three subsequent rotavirus seasons. We conclude that the abrupt appearance of this novel rotavirus serotype did not present a special threat to public health in the community.     

The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Microdissection genotyping of mixed glial and primitive neuroectodermal central nervous system neoplasm

A 22-year-old man with previous radiation treatment for childhood astrocytoma underwent resection of a right parietooccipital lesion. Histopathology revealed a malignant neoplasm with areas of astrocytic and primitive neuroectodermal components. To resolve the relationship and cellular origin, representative tissue was microdissected from several targets, obtaining a balanced mixture of each element. Nonneoplastic brain parenchyma was separately microdissected to determine polymorphic marker informativeness and to serve as an internal negative control. Despite the relatively small quantity of tissue removed for each microdissection target, sufficient material was available for reliable, balanced, polymerase chain reaction-format genotyping encompassing a panel of tumor suppressor genes and genetic loci associated with these forms of neoplasia. The findings revealed distinct discordant genotypic profiles for each of the neoplastic components. The efficacy of the approach used for molecular analysis of this complex neoplasm and the implication of the genotypic findings are discussed.     

Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.     

Comparison of the chemotactic responsiveness of two fibrosarcoma subpopulations of differing malignancy.

There are several points of similarity between the processes of cancer metastasis and inflammation. In both, cells circulate in the vasculature, arrest, and cross vessel walls, thereby entering the extravascular tissues. In vitro, leukocytes and some, but not all, tumor cells exhibit chemotaxis. Since the chemotactic response of leukocytes effect their transvascular migration, we propose that chemotactic responsiveness contributes to the ability of circulating tumor cells to localize in extravascular tissues. This study was done to seek a relationship between chemotactic responsiveness of tumor cells and their behavior in vivo. Two subpopulations of cells were isolated from a methylcholanthrene-induced fibrosarcoma. The two cell lines were compared with regard to their biologic behavior in vivo and their chemotactic responsiveness in vitro. In vivo one subpopulation was highly malignant. An injection of 2.0 x 10(5) cells into the footpad of syngeneic mice led to the development of primary tumors in 87% of the animals and lung metastases in 61% of the animals with primary tumors. This line demonstrated chemotaxis to a factor that behaved similarly in gel filtration and showed immunologic reactivity similar to that of a previously described tumor cell chemotactic factor derived from the fifth component of complement. In contrast, an injection of the same number of cells from the second subpopulation of fibrosarcoma cells led to the development of primary tumors in only 12% of syngeneic mice, and lung metastases did not occur. Neither this subpopulation nor normal embryonic fibroblasts demonstrated chemotactic responsiveness. We postulate that the ability of tumor cells to respond to specific chemotactic stimuli may be one of the many unique properties which distinguish malignant from benign tumor cells. This is the first report documenting the chemotactic responsiveness of non-ascites tumors and fibrosarcomas.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)_n repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)_n repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z = 1.91, p = 0.055). An excess of non-transmissions was detected for the 150 and 152 bp alleles (Z = −2.26, p = 0.023; Z = −2.20, p = 0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p = 0.011), and lower effort (p = 0.008), activation (p = 0.008) and attention (p = 0.01) cluster scores. We did not replicate association findings in the case–control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)_n repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.