Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry

Experimental intracerebral hemorrhage has been shown to cause extensive cerebral ischemia. This study was performed to ascertain the time course of these changes and also to examine the type of brain damage that may occur under such circumstances. Halothane anesthesia was induced in rats, and 25 microliter autologous blood was injected into the caudate nucleus; the effects were studied with autoradiographic measurement of local cerebral blood flow and capillary permeability, and also by light microscopy and histochemical techniques. Blood flow returned to normal or to slightly increased levels within the first 3 hours, and ischemic levels of flow were found to persist only to a marginal degree beyond 10 minutes after the lesions were made. Capillary permeability was maximum during the first 30 minutes after the hemorrhage and diminished with time. Structural evidence of ischemic damage was localized to the cortex overlying the hemorrhage, but was not seen in the caudate nucleus. Nevertheless, histochemical investigation did reveal an area of disturbed enzyme function in the striatum. This finding of biochemical disturbance without structural evidence of ischemic damage reveals that there is an area around the hematoma that, although demonstrating disturbed function, does not show structural damage, and the milieu of this partially injured brain may be implicated in the delayed development of the ischemic brain damage that follows intracerebral hemorrhage in man.     

A randomized clinical trial of prophylactic OKT3 monoclonal antibody in liver allograft recipients

Seventy-nine hepatic allograft recipients were randomized to receive either conventional immunosuppression, including cyclosporine, azathioprine, and steroids (41 patients), or investigational therapy in which OKT3 replaced cyclosporine during the first postoperative week (38 patients). Early rejection occurred in 29 patients (71%) in the conventional group and 15 patients (39%) in the OKT3 group. Posttransplantation renal dysfunction occurred in 12 patients (29%) in the conventional group and 6 patients (16%) in the OKT3 group. Mean initial hospital stay was 34.1 +/- 18.8 days in the conventional group compared with 29.1 +/- 16.8 days in the OKT3 group. Cumulative patient survival (mean follow-up, 17.8 +/- 7.1 months) was 73.2% (30/41) for the conventional group and 84.2% (32/38) for the OKT3 group. Prophylactic OKT3 is indicated especially for liver allograft recipients with other complicating conditions that make management of early rejection unusually difficult.     

History of clinical trials

Advances in medical treatments have occurred because of the application of new knowledge gained from clinical experiments conducted over the last 250 years. New sources of compounds with anti-tumor activity in human cancer are constantly under investigation. The development of a new drug is a complex process: screening, formulation, production, toxicology studies, FDA approval, and evaluation in phase I, II, and III clinical trials.     

Age-dependent capacity for somatosensory cortex reorganization in chronic spinal cats

Primary somatosensory cortex was mapped in chronic spinal cats that were spinalized (T12) at two weeks and 6 weeks of age. The magnitude of cortical reorganization is age-dependent. In cats spinalized at two weeks, extensive reorganization of the deafferented hindlimb region resulted in a second complete map of intact tactile input from the trunk and forelimb, while in cats transected at 6 weeks of age, trunk afferent input only partially activated the deafferented hindlimb region.     

Formation of interdental soft tissue defects after surgical treatment of periodontitis

This study monitored the development and repair of interdental soft tissue defects following surgical treatment of periodontitis in 21 patients. Open flap curettage was performed at 100 interdental areas with follow-up examinations 1, 3, and 6 months later. Interdental gingival contours were assessed both clinically and indirectly with silicone elastomer impressions from which stone models were obtained; defect depths were then calculated using the Reflex Microscope. Two types of defect were identified at the 1-month follow-up: 13 interdental clefts (mean depth, 1.8 mm); and 30 craters, (mean depth, 1.6 mm). Although clefts tended to persist, craters showed a strong tendency to repair. Thus, at the 6-month follow-up, the depths of clefts and craters were 1.3 mm and 0.7 mm respectively. The development of soft tissue defects did not appear to be related to the use of a periodontal dressing nor did the existence of an underlying bone defect appear to be of etiological importance. Pre-operative probing depths, however, were positively associated with the occurrence of soft tissue craters (P = 0.02). Pre-operatively, the overall mean probing depth and frequency of bleeding on probing were 5.3 mm and 100% respectively. At 6 months, these values were reduced to 2.0 mm and 22%. When clefts, craters, and interdental areas with no soft tissue defect were compared, no significant differences in probing depth reduction or frequency of bleeding were observed at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)     

Targets of herpes simplex virus type 1 infection in a mouse corneal model

Summary In animal models, spread of herpes simplex virus type 1 (HSV-1) from epithelial replication sites to the peripheral and central nervous system is known from analysis of individually dissected tissues. To examine virus spread in undissociated tissues, corneas of adult mice were inoculated with HSV-1. After 1 to 13 days groups of mice were perfused with formalin, and decalcified blocks of head and neck were embedded in paraffin. At intervals, serial sections were screened for HSV antigen. On days 1 and 2, viral antigen was restricted to cornea and conjunctiva but by days 3 and 4 was also seen in autonomic ganglia and the trigeminal system. On day 6, HSV antigen reached its maximum extent; infected sites included the trigeminal complex (ganglion, root, peripheral ophthalmic and maxillary branches and spinal nucleus and tract), ehtmoid sinus and olfactory buld, visual system, and autonomic ganglia (ciliary, pterygopalatine and superior cervical). Antigen progressively diminished on days 8 and 10, and was not detected on day 13. This method demonstrates a broader range of infected tissues and suggests a more complex pattern of HSV spread than has been previously recognized. Virus appears to reach the intracranial compartment by four different neural routes. When effects of higher and lower corneal inoculation doses were compared, a lower dose resulted in lower peak HSV titers in trigeminal ganglion and brain stem and later virus appearance in these tissues. Thus, dose may influence the kinetics of HSV spread from the peripheral inoculation site to the CNS.Supported in part by U.S.U.H.S. grant, R07396. the opinions or assertions contained herein are the private views of the authors and should not be construed as official or necessarily reflecting the views of the Uniformed Services University of the Health Sciences or Department of Defense. There is no objection to its presentation and/or publication     

Surgical approach to generalized lymphadenopathy in homosexual men

Sixty patients considered at risk for acquired immune deficiency syndrome (AIDS) were referred for evaluation of generalized lymphadenopathy. All patients were seropositive for antibody to human T-lymphotropic virus type III (HTLV-III). Multiple lymph node biopsies from different nodal areas were performed. The results were evaluated in order to see if the diagnostic yield is increased by the performance of multiple lymph node biopsies. In no case was additional diagnostic information provided by performing multiple biopsies. In patients with diffuse lymphadenopathy who are at risk for AIDS, single node excisional biopsy is indicated to rule out opportunistic infection or/and tumor.     

Enhanced restriction site mutation (RSM) analysis of 1,2-dimethylhydrazine induced mutations, using endogenous p53 intron sequences

The restriction site mutation (RSM) assay was used to studythe mutational sensitivities of three target regions of themurine p53 gene. The non-coding intron 6 target region was comparedwith the coding regions exon 4 and exon 5 with respect to theirrelative sensitivity to the induction of mutations by 1,2-dimethylhydrazine(DMH). Our results demonstrated that the majority of inducedmutations detected were in the intron 6 gene region. A totalof 15 enzyme-resistant restriction sites were detected in DMHtreated mice, nine of these in the intron 6 region, four inthe exon 4 region and two in the exon 5 region. The elevated sensitivity of the intron 6 region was exemplified by our detectionof spontaneous mutations in this region; two resistant restrictionsites were detected in untreated animals. No spontaneous mutationswere detected in either of the exon sequences studied here,nor have any been detected in exon targets in our previous invivo RSM analyses. The mutations induced by DMH were mostlyGC