Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.

PURPOSE: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated. RESULTS: Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients. CONCLUSION: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.     

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (   n = 16  ) and also from normal cervix ( n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.     

Disabled-1 is expressed in type AII amacrine cells in the mouse retina

The organization of several laminated structures in the brain is controlled by a signaling pathway activated by Reelin, a large glycoprotein secreted by pioneer neurons in the developing brain. Reelin binds to transmembrane receptors, including VLDLR and ApoER2, and stimulates tyrosine phosphorylation of Disabled-1 (Dab1), which associates with an NPxY motif present in the cytoplasmic domain of the receptors. Disruption of reelin, dab1, or both the vldr and apoer2 genes results in similar cell positioning defects in laminated brain regions including the cerebellum, hippocampus, and cerebral cortex. Although retinal ganglion cells express reelin during development, there is no obvious disruption of cell positioning in the retina of reeler mice. Here, we examine the expression pattern of Dab1 as a first step toward understanding the function of the Reelin signaling pathway in neural retina. Immunohistochemical analysis of the adult retina revealed that Dab1 is expressed in a specific type of amacrine cell. These cells display a narrow dendritic field and they project to two distinct sublaminae within the inner plexiform layer. Dab1 co-localizes with the high-affinity glycine transporter, indicating that these amacrine cells are glycinergic. Cells that express Dab1 are surrounded by dopaminergic fibers originating from wide-field amacrine cells. These features are characteristic of type AII amacrine cells described in other mammalian species. Analysis of the retina at several stages of development revealed that Dab1 is expressed shortly after birth during the time at which AII amacrine cells extend neurites and form synaptic connections in the inner retina. This raises the possibility that the Reelin/Dab1 signaling pathway contributes to formation of intraretinal circuitry in the neural retina.     

Reelin mRNA expression during embryonic brain development in the chick

The expression of reelin mRNA was studied during embryonic brain development in the chick, by using in situ hybridization. Reelin was highly expressed in the olfactory bulb and in subpial neurons in the marginal zone of the cerebral cortex. In the diencephalon, the ventral division of lateral geniculate nuclei and perirotundal nuclei were strongly positive. High levels of expression were associated with some layers of the tectum and with the external granule cell layer of the cerebellum. A more moderate signal was detected in the septal nuclei, hyperstriatal fields, retina, habenular nuclei and hypothalamus, in some reticular nuclei of the mid- and hindbrain, and in the spinal cord. Little or no expression was observed in the cortical plate, Purkinje cells, or the inferior olivary complex. Comparison with reelin expression during mammalian and reptilian brain development reveals several evolutionarily conserved features that presumably define a homology. In addition, significant differences are noted, particularly in telencephalic fields. Most importantly, the developing chick cortex does not exhibit high levels of reelin expression in subpial Cajal-Retzius cells characteristic of the mammalian brain. These observations are compatible with an action of reelin on adhesion and/or of nucleokinesis at the level of target cells. They further suggest that, whereas the telencephalon of birds and archosaurs evolved primarily from dorsal ventricular ridge derivatives in which reelin is probably secondary, the increase in number of reelin-positive cells, and amplification of reelin expression played a key part in the evolution of the cortex in the synapsid lineage leading to mammals.     

The overactive bladder in childhood: long-term results with conservative management

PURPOSE: Idiopathic detrusor overactivity has not been thoroughly investigated and its natural history remains largely anecdotal. Bladder overactivity resulting from a neurogenic, anatomical or medical condition has been well described. Therefore, we assessed the long-term results of conservative treatment of children with idiopathic symptomatic refractory detrusor instability. MATERIALS AND METHODS: We reviewed the records of 58 patients who had an isolated finding of uninhibited contractions on urodynamics performed for refractory enuresis and daytime wetting between 1988 and 1994. Study exclusion criteria were chronic urinary tract infection, neurological lesion, anatomical abnormality of the lower urinary tract and less than 12 months of followup. RESULTS: Of the 30 children who met our study inclusion criteria 26 (87%) had complete (21) or significant (5) symptom resolution. Average time to resolution was 2.7 years (range 0.2 to 6.6). Patients with a 50% to 90% bladder capacity expected for age were more likely to benefit from therapy than those with a bladder capacity outside of this range. Age and gender were not significant predictors of resolution although girls were more likely to have resolution than boys. CONCLUSIONS: Idiopathic detrusor instability is amenable to conservative management in the majority of patients during a prolonged period. We advocate thorough urological and urodynamic evaluation to identify idiopathic detrusor instability as an etiology of enuresis and daytime wetting in complicated cases.     

Prospective pricing system by diagnosis-related groups: comparison of federal diagnosis-related groups with high-risk obstetric care groups

Of 468 diagnosis-related groups identified by the federal government for Medicaid reimbursement, 15 are related to obstetric hospital care. Each diagnosis-related group is considered a distinct group in which cases are homogeneous with respect to resource consumption. Because the diagnosis-related group system is based primarily on data from community and secondary care hospitals, it does not differentiate sufficiently among high-risk obstetric patients seen at tertiary care institutions, such as Florida's Regional Perinatal Intensive Care Centers. We developed an alternative scheme for diagnosis-related groups, called obstetric care groups, using the federal diagnosis-related groups as the model from which to depart. Data collected for 4192 women during a 2 1/2-year period indicate that obstetric care groups provide more homogeneous groups than diagnosis-related groups for our population of high-risk patients. The obstetric care groups differentiate between no complications, one complication, and two or more complications, while the diagnosis-related groups differentiate only between no complications and one or more complications. Also, complications for obstetric care groups are based on only 19 diagnoses that contribute significantly to resource consumption, while the list of possible complications exceeds 200 for diagnosis-related groups. Although the obstetric care group classification system is simpler than that for diagnosis-related groups, it results in a more accurate reimbursement of hospitalization charges for high-risk obstetric care.     

Summer Research Training for Medical Students: Impact on Research Self‐Efficacy

There is a well‐documented shortage of physician researchers, and numerous training programs have been launched to facilitate development of new physician scientists. Short‐term research training programs are the most practical form of research exposure for most medical students, and the summer between their first and second years of medical school is generally the longest period they can devote solely to research. The goal of short‐term training programs is to whet the students’ appetite for research and spark their interest in the field. Relatively little research has been done to test the effectiveness of short‐term research training programs. In an effort to examine short‐term effects of three different NIH‐funded summer research training programs for medical students, we assessed the trainees’ (N = 75) research self‐efficacy prior to and after the programs using an 11‐item scale. These hands‐on training programs combined experiential, didactic, and mentoring elements. The students demonstrated a significant increase in their self‐efficacy for research. Trainees’ gender, ranking of their school, type of research, and specific content of research project did not predict improvement. Effect sizes for different types of items on the scale varied, with the largest gain seen in research methodology and communication of study findings.     

Postbiopsy renal transplant arteriovenous fistulas: color Doppler US characteristics

Color Doppler ultrasound (US) with point-spectral analysis was performed on eight patients with postbiopsy renal transplant arteriovenous fistulas. Waveform analysis of the supplying artery documented decreased resistive indices in all cases and increased flow velocities in seven. The peak-systolic flow velocity in the arteries supplying the fistulas ranged from 55 to 180 cm/sec (mean, 92 cm/sec), while the range in normal arteries was 20-52 cm/sec (mean, 32 cm/sec). The resistive indices of the arteries supplying the fistulas ranged from 0.31 to 0.50 (mean, 0.45), while the resistive indices of the normal arteries ranged from 0.60 to 0.92 (mean, 0.74). Arterialization of the venous waveform from the draining vein was also documented in all cases. In six cases, the increased flow velocities resulted in increased color saturation toward white in the supplying artery (n = 2) or in both the artery and the draining vein (n = 4), which was detectable on the realtime image. In six cases, flow turbulence resulted in localized tissue vibration, which appeared as random color assignment in extravascular renal parenchyma adjacent to the fistula. Knowledge of these imaging and Doppler characteristics should aid in the identification of renal transplant arteriovenous fistulas with color Doppler US.     

Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient.