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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 127 records · Page 7Linked to original sources

Patient acceptance of prefilled disposable vaginal applicator.

Patient acceptance of a new, compact, prefilled disposable vaginal applicator was tested in an open study in which 2% butoconazole cream was used for the treatment of vulvovaginal candidiasis. Twenty nonpregnant patients with clinical signs and symptoms of candidiasis and microscopic identification of Candida in wet smear were treated for 3 days and then asked to rate the convenience of and their acceptance of the prefilled vaginal applicator. No adverse events were reported. All of the patients readily accepted the idea of a prefilled applicator and judged the shape and surface of the test applicator to be comfortable and the applicator to be easily inserted. Patients judged this applicator to be the most convenient and least messy when compared with other commercially available, reusable, or prefilled disposable applicators.

Administration, Intravaginal↗

Cell-sized microspheres in the hippocampus show cleavage planes and passive displacement.

Fluorescent microspheres (6 or 10 micron in average diameter) dispersed in fluid were injected into the hippocampus, neocortex or striatum. In the hippocampus the microspheres were located in one of three cleavage planes. Cleavage planes were found above the alveus, in the obliterated hippocampal fissure and on the hilar side of the dentate granule cells. When the injections were made into the infragranular cleavage plane, the adjacent granule cells degenerated, presumably because the cavity separated the axons from their cell bodies. Some microspheres were passively displaced beyond the boundary of the injection site. If the microspheres gained access to the subarachnoid space, some of the displaced microspheres were found at considerable distances from the injection site. There were no cleavage planes in neocortex or striatum but there was passive displacement of microspheres into the host parenchyma. In cell suspension transplants, the passive displacement of cells should be distinguished from migration and the possibility of a widespread distribution of transplanted cells needs to be considered.

Animals↗

Bone marrow transplantation for poor prognosis neuroblastoma.

These studies suggest that intensive chemoradiotherapy (eg., VAMP-TBI), if given relatively soon after diagnosis and before development of progressive disease, improves long-term survival for patients with advanced neuroblastoma. Although this particular therapy is not useful for those who already have developed progressive disease, other intensive regimens may warrant testing in this latter group of patients. Our current study is testing aggressive induction chemotherapy, ex vivo purging of autologous marrow, and VAMP-TBI followed by BMT. Because of the increasing risk of progressive disease with time after diagnosis, we recommend beginning the BMT phase by 20 weeks after diagnosis. This should result in 85% of newly diagnosed patients entering the BMT phase without progressive disease; and, with fewer toxic deaths, 90% should survive the BMT phase. Thus, approximately 70% of patients could be disease-free survivors 8-9 months after diagnosis. Because a significant number of patients still develop progressive disease during induction or after BMT, efforts are being made to improve induction and pretransplant therapies and to identify prognostic factors. If modifications of the current regimens do not decrease the rate of progressive disease, it may be necessary to develop additional or different therapy for patients identified to be at high risk. Hopefully, new strategies will further increase the percentage of patients with tumor-free survival.

Bone Marrow Transplantation↗

Immediate and delayed bronchoconstriction after exercise in patients with asthma.

Although an immediate asthmatic response after exercise is known to occur in some patients with asthma, the existence of a delayed asthmatic response after exercise is controversial. Accordingly, we studied 53 patients who had an immediate mean (+/- SD) decrease in forced expiratory volume at one second (FEV1) of 36 +/- 13 percent, which was maximal 13 +/- 12 minutes after the completion of treadmill exercise. Eight of these patients also had a delayed asthmatic response (a 32 +/- 5 percent decrease in FEV1 occurring 5.0 +/- 1.8 hours after exercise). During a control day, on which the FEV1 was measured serially but no exercise was performed, the same delayed asthmatic response was observed in all but one patient. This finding suggests that the delayed asthmatic response observed in these patients after exercise was not specifically related to the performance of exercise. We conclude that in patients who have bronchoconstriction immediately after exercise, a second asthmatic response occurring later after the exercise is uncommon.

Adolescent↗

Time course of reactive synaptogenesis in the subcortical somatosensory system.

These experiments were designed to determine when synaptogenesis begins in the adult rat ventral posterolateral nucleus of the thalamus following lesions of the dorsal column nuclei. Given the relatively uncomplicated structure of the neuropil in the ventral posterolateral nucleus of the rat, the specificity of reactive synaptogenesis of the lemniscal input and the effect of the loss of lemniscal terminals on terminals from other sources could be determined. By use of morphometric analysis of electron micrographs, the numerical density of the 3 terminal types in the neuropil was determined at a series of postlesion survival times ranging from 12 hours to 50 days. Synaptogenesis began about 30 days after the lesions of the dorsal column nuclei and was complete by 50 days. The slow onset of synaptogenesis was in response to a loss of the lemniscal terminals, which account for only 3% of the total number of synapses in the ventral posterolateral nucleus. The low level of synaptogenesis early in the recovery process differs from the recovery seen in other central nervous system sites, which show an early rapid increase in synapses in response to much greater denervation. The loss of lemniscal terminals has relatively little effect on the numerical density or distribution of the terminals of other types. The new terminals that are formed come both from axons that originate from the undamaged portion of the dorsal column nuclei and from axons originating in the spinal cord.

Afferent Pathways↗

Time course of the reaction of glial fibers in the somatosensory thalamus after lesions in the dorsal column nuclei.

These experiments were designed to examine the relationship of glial hypertrophy to the time course of reactive synaptogenesis in the ventral posterolateral nucleus of the rat thalamus after lesions in the dorsal column nuclei. Because synaptogenesis is delayed for 30 days following lesions of the dorsal column nuclei, the initial hypertrophy of the glial processes in response to degeneration can be separated temporally from synaptogenesis. Glial hypertrophy was determined by measuring the relative area of neuropil occupied by profiles of glial processes on electron micrographs. The initial glial hypertrophy reached its peak 2 days after the lesion. However, at the time when synaptogenesis began, the area of neuropil occupied by glial processes was less than normal. When synaptogenesis was complete, the area of glial profiles also returned to normal. The role of glia in synaptogenesis was clearly different from its role in response to degeneration. In those systems such as the hippocampus, in which reactive synaptogenesis starts early in the recovery sequence, the relationship of glia to synaptogenesis may be masked by the glial response to degeneration. Hypertrophy of glial processes after lesions of other afferent pathways to the ventral posterolateral nucleus was compared to the hypertrophy following lesions of the dorsal column nuclei in order to see if there was a special relationship between glia and the lemniscal afferents to the ventral posterolateral nucleus. Lesions were placed in the medial lemniscus, somatosensory cortex, and the mesencephalon in addition to the dorsal column nuclei. The area of neuropil occupied by the glial processes expanded markedly after each of the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Delayed surgery and bone marrow transplantation for widespread neuroblastoma.

From 1983 to 1986, 21 patients with poor prognosis neuroblastoma were treated with bone marrow transplantation. This regimen included induction chemotherapy, delayed surgical resection, local irradiation, and intensive chemoradiotherapy followed by infusion of allogeneic or autologous marrow. This therapeutic approach resulted in a 57% long-term survival rate (follow-up: 14-48 months), which appears to be approximately three times superior to conventional chemotherapy in a comparable group of children. In addition, complete resection was possible in 11 of 17 patients operated on after induction therapy. Recurrence in the primary site after bone marrow transplantation occurred in only one of 18 evaluable patients. Thus, this approach almost always eradicates primary tumor in patients with neuroblastoma with advanced disease.

Adolescent↗

Xenografts of brain cells labeled in cell suspensions show growth and differentiation in septo-hippocampal transplants.

Embryonic mouse brain cells from the basal forebrain region were labeled in cell suspensions and transplanted into the denervated hippocampal formation of adult rats. Many labeled cells had the appearance of typical pyramidal neurons with dendrites that had both growth cones and neurites. Labeled neurons and glia were seen at several sites in the hippocampal formation. The neurons were located predominantly along the dentate granule cell layer and the pyramidal neurons had a preferred orientation of their apical dendrites toward the molecular layer. Since it was rare to see a surviving labeled neuron within the injection site, migration away from the injection site seemed important for survival of the cells. The methods used in these experiments should become an important adjunct to the methods for studying the migration, differentiation and growth of neurons and glia.

Animals↗

Spontaneous regression of a choroidal melanoma.

Although spontaneous regression of uveal malignant melanoma is rare, its occurrence is not uncommon in cutaneous melanomas. We report a 15-year follow-up of an enlarging posterior pigmented tumor. It initially appeared to spontaneously regress into a flat chorioretinal scar, but, ten years later, it grew markedly and the eye was enucleated. Histopathologic changes similar to those found in regressed cutaneous melanomas were located in the region of the chorioretinal scar.

Adult↗

Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial.

The effects of ex-vivo depletion of T lymphocytes from donor bone marrow using a monoclonal anti-T-cell antibody (CT-2) and complement on the outcome of allogeneic bone marrow transplantation was evaluated in a prospective, randomized, double-blind study of 40 patients with leukemia. Patients receiving T-cell-depleted bone marrow had a lower incidence of acute graft-versus-host disease than control patients (3 of 20 compared with 13 of 20; p = 0.004), and mortality due to acute graft-versus-host disease was reduced. Five patients in the T-cell-depletion group developed graft failure; all control patients had sustained engraftment (p less than 0.05). Clinically apparent relapse of leukemia occurred in 7 patients from the T-cell-depletion group and in 2 controls (p, not significant). Cytogenetic evidence of residual leukemia was also detected in the 5 patients with graft failure without overt relapse. Infections and overall survival were similar in the two groups. The effects of T-cell depletion on engraftment and recurrence of leukemia require further evaluation.

Actuarial Analysis↗