The geographic and functional distribution of black physicians: some research and policy considerations

Studies of the geographic and functional distribution of physicians rarely include race of the physicians as a study variable. For black physicians, there are some rather strong justifications for doing just that: 1) their services are directed almost exclusively to black and often medically underserved communities; 2) recent efforts to reduce constraints to medical education based on race, sex, ethnicity, and income have resulted in a substantial increase in the proportion of black medical students; 3) inferring about black physicians from information on the general population of physicians given the differences in biographical and experimental characteristics is tenuous at best. Hence, an adequate information base and focused conceptualization on the educational and career patterns of black physicians are indicated. At the policy level there is a need to clarify the relationship between equity in educational (and career) opportunity and efforts to redistribute physicians.     

Neuroadaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment

The expression of glutamate receptor/subunit mRNAs was examined 3 weeks after discontinuing 1 week of daily injections of saline or cocaine. The level of mRNA for GluR1-4, NMDAR1, and mGluR5 receptors was measured with in situ hybridization and RT-PCR. In nucleus accumbens, acute cocaine treatment significantly reduced the mRNA level for GluR3, GluR4, and NMDAR1 subunits, whereas repeated cocaine reduced the level for GluR3 mRNA. Acute cocaine treatment also reduced the NMDAR1 mRNA level in dorsolateral striatum and ventral tegmental area. In prefrontal cortex, repeated cocaine treatment significantly increased the level of GluR2 mRNA. The GluR2 mRNA level was not changed by acute or repeated cocaine in any other brain regions examined. Repeated cocaine treatment also significantly increased mGluR5 mRNA levels in nucleus accumbens shell and dorsolateral striatum. Functional properties of the ionotropic glutamate receptors are determined by subunit composition. In addition, metabotropic glutamate receptors can modulate synaptic transmission and the response to stimulation of ionotropic receptors. Thus, the observed changes in levels of AMPA and NMDA receptor subunits and the mGluR5 metabotropic receptor may alter excitatory neurotransmission in the mesocorticolimbic dopamine system, which could play a significant role in the enduring biochemical and behavioral effects of cocaine.     

Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and Is essential for virus replication

The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b-encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625-6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864-4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln-2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991-997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837-->Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus.     

Petit mal status in a patient with chronic renal failure

A 39-year-old woman with traumatic spinal paraplegia and chronic renal failure had peritoneal dialysis for acute renal failure precipitated by a bout of urinary tract infection. Two weeks after the dialysis she lapsed into coma for a few days. An electroencephalogram indicated petit mal stupor as it showed generalized epileptic discharges during the initial period of her coma.     

Intracardiac thrombus trapped in a patent foramen ovale

We describe a case of impending paradoxical embolism due to a thrombus trapped in a patent foramen ovale in a 22-year-old woman. Transthoracic and transesophageal echocardiography detected the thrombus. She was operated on and discharged asymptomatic.     

Effect of dose, schedule, and route of administration on the in vivo toxicity and antitumor activity of two activated sulfhydryl derivatives of cyclophosphamide

Two cyclophosphamide (CP) derivatives, 4-S-(hexane-6-ol)-sulfidocyclophosphamide (C-1) and 4-S-(propionic acid)-sulfidocyclophosphamide (C-2), that hydrolyze spontaneously under physiological conditions to 4-hydroxycyclophosphamide, are compared to CP for antitumor activity in male C57BL/6 x DBA/2 F1 mice with ascites L1210 leukemia or solid Lewis lung carcinoma. When C-1 or C-2 is administered i.p. as a single injection at 10% lethal dose (approximately LD10) to mice bearing L1210 (1 x 10(5) cells i.p.), early treatment produces a 5- to 6-log tumor cell kill and results in substantial numbers of long-term survivors (greater than or equal to 30 days). Such antitumor activity is comparable to that of CP treatment. However, i.p. administration of either sulfido derivative produces liver atrophy and fibrosis of hepatic capsular structures. Hepatotoxicity is eliminated if single-dose C-2 (less than or equal to LD10) is administered i.v.; however, when administered by this route, C-2 results in only a 1-log cell kill of i.v. implanted leukemic cells as compared to the 4-log tumor cell kill obtained with CP given i.v. In addition to hepatotoxicity, C-2 causes an acute and dose-limiting toxicity in mice, manifested by severe muscular spasms and cessation of breathing. In the treatment of advanced L1210, C-2 shows no therapeutic advantage over CP. When mice bearing s.c. Lewis lung carcinoma receive early i.p. treatment with CP, C-1, or C-2, each drug results in long-term tumor-free survivors. However, CP (< LD10) consistently cures all mice, whereas C-1 or C-2 (approximately LD10) produces only 10 to 30% tumor-free survivors. These data suggest that, in the L1210 and Lewis lung tumor systems studied, the two activated CP derivatives offer no therapeutic advantage over CP. In addition, two forms of toxicity occur with these derivatives that do not occur with CP.