Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide

A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor.     

Partial k-space reconstruction in single-shot diffusion-weighted echo-planar imaging.

Partial k-space sampling is frequently used in single-shot diffusion-weighted echo-planar imaging (DW-EPI) to reduce the TE and thereby improve the SNR. However, it increases the sensitivity of the technique to bulk rotational motion, which introduces a phase gradient across the tissue that shifts the echo in k-space. If the echo is displaced into the high spatial frequencies, conventional homodyne reconstruction fails, causing intensity oscillations across the image. Zero-padding, on the other hand, compromises the image resolution and may cause truncation artifacts. We present an adaptive version of the homodyne algorithm that detects the location of the echo in k-space and adjusts the center and width of the homodyne filters accordingly. The adaptive algorithm produces artifact-free images when the echo is shifted into the high positive k-space range, and reduces to the standard homodyne algorithm in the absence of bulk motion.     

Gastric Epithelioid Leiomyosarcoma: A Curable Gastric Neoplasm

This is the first case report of the preoperative diagnosis of a gastric epithelioid leiomyosarcoma by percutaneous needle biopsy. Preoperative diagnosis facilitated curative surgical resection. Patients may present without symptoms or may report symptoms of peptic ulcer disease or gastrointestinal bleeding. Upper gastrointestinal series is the most useful radiological tool for detecting these lesions. Ultrasound and CT play a useful role in documenting the origin of these large masses, as well as their spread. Endoscopy is being used with increasing frequency, but because these are submucosal lesions diagnosis cannot easily be made through the endoscope. Pathologically, these tumors can be subdivided histologically into a benign epithelioid leiomyoma and two varieties of malignant epithelioid leiomyosarcoma. Prognosis correlates with histological features. Complete surgical resection is the treatment of choice. Chemotherapy or radiotherapy have no proven efficacy in treating epithelioid leiomyosarcoma. Unlike most other gastric malignancies, a favorable prognosis follows successful resection.     

The effects of photoperiod on olfactory c-fos expression in prairie voles,Microtus ochrogaster

Reproduction stops among the majority of prairie voles (Microtus ochrogaster) during the winter. Short day lengths suppress male reproductive function dramatically in the laboratory, but photoperiod exerts only subtle effects on female reproductive function. Thus, the regulation of seasonal breeding in this species remains partially unspecified. In contrast to commonly studied rodents, female prairie voles do not undergo spontaneous estrous cycles; rather, they are induced into estrus by exposure to chemosignals expressed in conspecific male urine. In the present study, the hypothesis was tested that seasonal breeding among female prairie voles in the field reflects photoperiod-mediated changes in the responsiveness of the chemosensory system to male urine. Responsiveness was assessed by localizing the product of the c-fos immediate early gene with an immunocytochemical procedure. Female prairie voles were maintained in either long (LD 16:8) or short (LD 8:16) photoperiods from birth until adulthood, and exposed to either male urine or skim milk. Immunocytochemistry forfos protein revealed an increased number of immunoreactive cells within the accessory olfactory system of female prairie voles, including the accessory olfactory bulbs, granule cell layer, as well as the medial and cortical divisions of the amygdala 1 h after exposure to a single drop of urine as compared to individuals exposed to skim milk. The number of immunoreactivefos cells induced in females by conspecific male urine was also affected by photoperiod; short day females displayed fewer immunoreactivefos neurons in the accessory olfactory system as compared to long-day animal. Taken together, these results indicate that similar mechanisms underlie the responses of different rodent species to the chemosignals of conspecifics and that the pattern offos expression observed in the present study has functional significance for the regulation of reproduction in prairie voles.     

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.     

Guinea pig maximisation test for skin sensitisation: the use of fewer test animals

Current European Community (Annex V) guidelines recommend the use of 20 test animals in the guinea pig maximisation test for skin sensitisation. The suitability, for classification and labelling purposes, of reducing the number of test animals has been examined by analysing the results of 40 studies submitted to the Health and Safety Executive, and by the use of a mathematical model. Our results suggest that in most cases an experiment with ten test animals can be used to determine satisfactorily whether a substance should be labelled with the risk phrase may cause sensitisation by skin contact. However, serious consideration should be given to the need for additional investigation if two or three of the ten test animals show a sensitisation response. The highest nonirritant concentration of a substance should be used at challenge. Clearer guidance in Annex V on evaluating challenge responses would be beneficial.     

Origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and the pulvinar in the rabbit

The origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and to the pulvinar in Dutch-belted rabbits were investigated using horseradish peroxidase (HRP) methods. Following injections of HRP in the dorsal lateral geniculate nucleus, retrogradely labeled neurons were found in the upper two-thirds of the stratum griseum superficiale of the ipsilateral superior colliculus. Most of the labeled somata were spindle-shaped, and their major axes tended to be perpendicular to the surface of the superior colliculus. In contrast, following injections of the pulvinar, labeled neurons were found in the lower third of the ipsilateral stratum griseum superficiale. In these cases, the labeled somata were larger than those labeled following dorsal lateral geniculate injections and were multipolar in shape.     

PSYCHOPHYSIOLOGY AND MEDICINE

Psychophysiology is just as closely related to internal medicine as it is to psychiatry. “Psychological variable” has two distinct meanings: a) an external sensory stimulus, or b) an organismic state described in psychological language. “Psychological” and “Physical” are names of two different languages. There is no such thing as a non-physical illness. Asking whether emotions cause diseases, or diseases cause emotions, leads to many difficulties and is unprofitable. It is far more useful to ask about stimulus-response relationships. There are more kinds of specificity relations in psychophysiology and psychosomatic medicine than are usually recognized, and the usual specificity statements in psychosomatic medicine are not concerned with I-R or S-R specificity. There are many problems in medicine which psychophysiology could help to solve.