An autoradiographic study of the organization of intrahippocampal association pathways in the rat

The longer associational connections of the hippocampal formation have been studied autoradiographically in a series of adult rats after small injections of ³H-amino acids into each of its various cytoarchitectonic fields. The major findings can be summarized as follows. The dentate gyrus projects in a topographically ordered manner upon the pyramidal cells of the regio inferior by way of the supra- and infrapyramidal bundles of mossy fibers. Certain cells in the hilar region of the dentate gyrus (which operationally may be defined as constituting field CA₄ of Ammon's horn) give rise to a hippocampodentate projection to the inner one-quarter of the molecular layer of the dentate gyrus. Either the same or closely related cells give rise to fibers which join the Schaffer collateral system from field CA₃ to the stratum radiatum and stratum oriens of the regio superior. The regio inferior is also characterized by a longitudinally directed associational bundle which runs throughout the septo-temporal extent of the hippocampus and is centered in the region of subfield CA_3a. The regio superior has no reciprocal projection to the regio inferior but sends a substantial projection back to the subiculum and to the entorhinal area. There is also a projection to the subiculum from the regio inferior, and the subiculum itself probably contributes significantly to the projection to the entorhinal and perirhinal cortices. There is a striking parallelism between certain of these associational connections and the commissural projections to the hippocampus and dentate gyrus. Each cytoarchitectonic field that contributes a commissural projection also gives rise to an ipsilateral associational pathway which in its intrahippocampal course and its mode of termination exactly matches that of the commissural projection, although in general, the associational connections are more extensive in their distribution along the septo-temporal extent of the hippocampus than the corresponding commissural connections. The reverse is not true; there are a number of associational projections which are not paralleled by commissural projection. All of the associational projections are topographically arranged, but those which extend across the transverse axis of the hippocampus usually show considerable divergence so that afferents from different levels overlap fairly considerably within their respective projection fields.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

Using community data to improve community care: A patient information system based on residential area characteristics

Conventional patient information systems generally ignore the characteristics of patients' residential communities in favor of individual characteristics. This omission precludes them from yielding information about issues of public health importance, i.e., the impact service organizations have on the communities they are supposed to serve.The University Services Epidemiologic Reporting System (USERS) is a prototypical community-based patient information system. It collects individual data about patients' residences and movements in and out of service facilities and integrates them with a specially developed residential area characteristic data base to produce reports that could be useful in applying epidemiology to solving practical health delivery problems. The USERS has proven to be both useful and economical in its trial context. Therefore, the implementation of the operational procedures detailed in the article promises a useful adjunct to the planning and operation of community-oriented human service systems in other places.Maurice S. Satin, Ph.D., Charlotte Monetti, B.A., and Elaine Brimer, B.A., are affiliated with the Division of Mental Health Care Systems, Long Island Research Institute, New York State Office of Mental Health. Dorothy Goldstein, Ph.D., is affiliated with the Department of Program Evaluation, Central Islip Psychiatric Center. Leon Hankoff, M.D. and Morton G. Miller, M.D. are affiliated with the Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook. Reprint requests may be addressed to Maurice S. Satin, Ph.D., Long Island Research Institute, Health Sciences Center T-10, Stony Brook, NY 11794.     

Role of intravesical mitomycin c in management of superficial bladder tumors

Forty-three patients with biopsy-proved Stage O or A transitional cell carcinomas of the bladder, whose tumors were not amenable to transurethral resection, received mitomycin C intravesically at weekly intervals for eight treatments. Five different drug doses were used (20, 25, 30, 40, and 60 mg.). Best response rates occurred at doses of 30 mg. or higher. Complete responses occurred in 49 per cent of patients, partial responses in 30 per cent, and improvement in 5 per cent, for an over-all effective rate of 84 per cent. Responses were achieved regardless of tumor extent as long as individual tumors were 1 cm. or less in diameter. Toxicity was minimal. The necessity for maintenance therapy in complete responders remains to be proved.     

Telomere-mediated mitotic disturbances in immortalized ovarian epithelial cells reproduce chromosomal losses and breakpoints from ovarian carcinoma

Ovarian carcinomas (OCs) often exhibit highly complex cytogenetic changes. Abnormal chromosome segregation at mitosis is one potential mechanism for genomic rearrangements in tumors. In this study, OCs were demonstrated to have dysfunctional short telomeres, anaphase bridging, and multipolar mitoses with supernumerary centrosomes. When normal human ovarian surface epithelial (HOSE) cells were transfected with human papilloma virus 16 e6/e7 genes and subsequently driven into telomere crisis, the same set of mitotic disturbances occurred in a distinct sequence, initiated by telomere dysfunction, followed by anaphase bridging, and then supernumerary centrosomes and multipolar mitoses. The anaphase bridges resolved either by kinetochore-spindle detachment, corresponding to whole-chromosome losses in the HOSE karyotypes, or by extensive fragmentation of intercentromeric DNA sequences, corresponding to a high frequency of pericentromeric rearrangements. At later passages, the high degree of instability at telomere crisis was moderated by telomerase expression and centrosome coalescence, ultimately leading to a level of mitotic instability that was highly similar to that in OC cell lines and to complex karyotypes that were similar to those observed in high-grade OCs. This suggests that a significant proportion of the structural chromosome changes and genomic losses in OC are caused by a specific sequence of mitotic disturbances triggered by telomere crisis. That the model did not produce any of the whole-chromosome gains observed in OC indicates that these changes develop through a different mechanism.     

Consumer views of representative payee use of disability funds to leverage treatment adherence

OBJECTIVE: Although representative payee arrangements are common among people with psychiatric disabilities, only a small body of research has investigated how consumers feel about representative payees' use of disability funds to attempt to improve treatment adherence. METHODS: Consumers who were in treatment for a recently documented diagnosis of schizophrenia or a related disorder (N=104) were interviewed to assess their perceptions of the use of disability funds and other legal pressures to attempt to improve treatment adherence. RESULTS: Most consumers in the sample (65 percent) did not agree that withholding money was a useful method to improve treatment adherence. Multivariate analyses indicated that participants were more likely to agree that use of money as leverage was helpful if they also felt that other legal pressures were helpful for improving adherence and if they felt free to do as they wanted regarding their mental health treatment. On the other hand, participants were less likely to endorse the benefits of money used as leverage if they had at least a high school education and if they reported abusing substances in the past month. CONCLUSIONS: The results of this study point to factors that mediate the potentially negative effects of perceived coercion that are sometimes associated with representative payee arrangements. Leverage of disability funds will likely have an optimal effect if combined with efforts to enhance a sense of self-determination. Conversely, consumers with more education may be less open to this practice, possibly because of perceived stigma related to not being able to control their own finances.     

Adjunctive treatment with mianserin enhances effects of raclopride on cortical dopamine output and, in parallel, its antipsychotic-like effect

Clinical studies indicate that adjunctive treatment with the antidepressant drug mianserin, a 5-hydroxytryptamine (5-HT)_2A/C receptor antagonist and an α₂- and α₁-adrenoceptor antagonist, may enhance the effect of conventional antipsychotic drugs in schizophrenia, in particular on negative symptoms such as withdrawal retardation, akathisia, and some aspects of cognitive impairment. Here, we have examined the effect of mianserin in combination with the selective dopamine (DA) D_2/3 receptor antagonist raclopride on conditioned avoidance response (CAR), a preclinical test of antipsychotic efficacy with high predictive validity; catalepsy, a preclinical test of extrapyramidal side effect liability; and DA output in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively. Mianserin (5 mg/kg intraperitoneal) significantly enhanced the suppressant effect of a low dose of raclopride (0.1 mg/kg subcutaneous) on CAR without any increase in catalepsy. Administration of raclopride to rats pretreated with mianserin resulted in a large enhancement of DA output in the mPFC and, at the same time, a small but significant reduction in the raclopride-induced DA output in the NAC. These experimental results indicate that adjunctive treatment with mianserin to a typical D₂ antagonist generates an atypical antipsychotic profile.     

The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.