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Biomedical subjects

J Freedman

Publications and source records attributed to J Freedman.

At least 127 records · Page 7Linked to original sources
PubMed1990

Histopathologic study of the Molteno glaucoma implant in three patients.

Three eyes with the Molteno glaucoma implant (one eye with epithelial downgrowth, one eye with iridocorneal endothelial syndrome, and one eye with aphakia and glaucoma) were enucleated two to six years after implantation. Histopathologic examinations disclosed no evidence of erosion of sclera or conjunctiva of the eye by the glaucoma implant device. In the outer layers of the bleb wall, few and mostly degenerated inflammatory cells were present, which represented a minimal inflammatory reaction. Scanning electron microscopy of the tubes in these three patients showed that the tube was intact, patent, and without signs of degradation. The tube entering into the anterior chamber caused no appreciable inflammation and maintained its patency even when downgrowth epithelial cells lined the anterior chamber. The Molteno plate induced little or no inflammatory reaction. Therefore, the Molteno glaucoma implant is a useful device for patients with high risk for failure after surgery for glaucoma.

Aged↗
PubMed1990

Acute leukemia evolving from multiple myeloma and co-expressing myeloid and plasma cell antigens.

This report describes the development of acute myeloblastic leukemia in a patient after long-term alkylator therapy for multiple myeloma. Despite chromosome deletions -5, -7, the patient lacked the histochemistry and clinical findings characteristic of therapy-induced leukemia. In double-labeled surface marker studies by flow cytometry, the leukemic blast cells co-expressed myeloid and plasma cell surface markers. The findings may support the hypothesis of a single stem cell abnormality's being responsible for both the malignant plasma cells and the myeloid leukemic cells.

Acute Disease↗
PubMed1989

Immunohistochemical and behavioral analysis of spinal lesions induced by a substance P antagonist and protection by thyrotropin releasing hormone.

Using behavioural, morphological and immunohistochemical analysis, the effect of intrathecal administration of a substance P antagonist, Spantide [D-Arg1, D-Trp7,9, Leu11)-SP), was studied. Antisera raised against markers for motoneurons, local spinal neurons, descending bulbospinal systems and primary afferents were used. The effect of some drugs, including thyrotropin releasing hormone (TRH), on Spantide-induced effects were also analyzed. After injection of 2 micrograms of Spantide at the lumbar level, a marked necrosis of the spinal cord was observed extending for about 5-6 segments, affecting mostly the ventral horns. Thus, calcitonin gene related peptide (CGRP)-like immunoreactivity (LI) in motoneurons completely disappeared and no motoneurons could be seen in cresyl violet-stained sections. The first changes were observed 6 h after Spantide injection and at 24 h a complete necrosis was seen. Marked reductions in the number of 5-hydroxytryptamine (5-HT)- and substance P-positive fibers were also observed. The effects were less dramatic in the dorsal horns, but at the site of maximal effects there was a disturbance also of CGRP-, substance P-, and neuropeptide tyrosine (NPY)-positive fibers in the superficial layers of the dorsal horn. These effects could be completely counteracted by multiple intravenous injections of TRH as well as with 5-methoxy-N, N-dimethyltryptamine (5-MeDMT), a 5-HT agonist. The behavioural analysis showed parallel changes, with permanent motor impairment after Spantide-treatment and complete absence of these symptoms when TRH or 5-MeDMT was given in addition. Finally, the effect of Spantide on 5-HT, noradrenaline, substance P and CGRP levels was measured biochemically. The present results are discussed in the light of recent findings that Spantide can cause a dramatic reduction in spinal blood flow.

Animals↗
PubMed1989

Distribution of TRH-like immunoreactivity with special reference to coexistence with other neuroactive compounds.

During the last years, several important advancements have been made that are of importance for our understanding of the distribution and localization of neurons and cells producing TRH-LI. As detailed in other chapters in this volume, the precursor for TRH has been characterized that has allowed production of antibodies raised against specific sequences of this precursor. This, in turn, has provided new tools for the immunohistochemical elucidation of TRH systems in the CNS. The TRH precursor has also been cloned, leading to possibilities for studying the localization of TRH mRNA with in situ hybridization. Finally, as shown in this paper, improvement of the fixation technique has made it possible to visualize extensive TRH-immunoreactive cell body and fiber systems with antiserum raised against the TRH tripeptide. The results from the latter studies and those with antisera directed to the TRH precursor and in situ hybridization are in good agreement, with some minor exceptions. It should be pointed out that some of the systems described here, for example TRH positive-cell bodies in cortical areas and the hippocampal formation, contain only a very weak immunoreactivity. As always with immunohistochemical techniques, the possibility of crossreactivity with TRH-like peptides or TRH-like sequences within larger proteins must be considered. The present results confirm the presence of TRH-LI in the insulin-producing beta cells of the pancreas, which with the improved technique can be demonstrated also in early adulthood in rats and guinea pigs. Moreover, it could be established that TRH-LI is present in neurons in the gastrointestinal tract as well as in a population of endocrine cells in the antrum of the stomach of the guinea pig. These cells seem at least partly to be identical to the well-known gastrin-producing cells. TRH-LI has been observed to occur in neurons already containing a classical transmitter and/or other peptides. Of particular importance here seems to be a descending bulbospinal system that in addition to TRH co-contains 5-HT, substance P-LI, galanin-LI, human growth hormone immunoreactive material, and proctolin-like material. The significance of this coexistence is not well understood, but interesting interactions have been observed. Attempts to manipulate the TRH phenotype in these medullary neurons by transplantation to other sites in the brain has so far shown that the expression of this peptide seems fairly stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Prevention of tumor growth and enhancement of cell-mediated immunity by an antigen-specific contrasuppressor factor from a T cell hybridoma.

We have produced a contrasuppressor T cell hybridoma which has positive effects on multiple forms of cell-mediated immunity. First of all, it protects the adoptive transfer of contact sensitivity from suppressor cells and factors. In addition, TcsF modifies the response to normally tolerogenic administrations of hapten, leading mice to develop contact sensitivity and CTL activity instead of tolerance. Most relevant to this conference, mice which have been both treated with AF5.C6 TcsF and painted with TNCB resist challenge with highly malignant TNP-modified tumors. These experiments suggest a decisive role for contrasuppression in tumor rejection.

Animals↗
PubMed1988

Intraarticular methylprednisolone therapy in hemophilic arthropathy.

This small pilot study examined the use of intraarticular methylprednisolone in hemophilic synovitis. Nineteen joints in ten adult hemophiliacs were studied. There was subjective improvement at 24 hr following injection in 79% of joints injected, and the improvement persisted up to 8 wk in 58%. The number of hemarthroses decreased following intraarticular steroids (mean of 7.7 bleeds in the 8 wk prior to injection versus a mean of 1.9 bleeds in the 8 wk following injection). Similarly the amount of clotting factor used for the injected target joint decreased from a mean of 7,616 units to 2,315 units postinjection (p less than .001). Improvement correlated with presence of synovitis but not with radiologic stage of the joint. Aspirated synovial fluids were analyzed and showed characteristics consistent with low-grade inflammation. These preliminary observations suggest that intraarticular corticosteroid injection may be a useful therapeutic tool in the medical management of hemophilic arthropathy.

Adult↗
PubMed1988

Random donor platelet crossmatching: comparison of four platelet antibody detection methods.

The standard lymphocytotoxicity assay (LCT), a biotin-avidin enzyme immunoassay (ELISA), platelet suspension immunofluorescence test (PSIFT), and platelet radioactive antiglobulin test (PRAT) were examined in prospective crossmatching for selection of compatible random donor platelets for refractory patients. One hundred seven episodes of pooled random donor platelet transfusions were evaluated in 26 patients. There was good reproducibility of results by individual techniques. Concordance of results by the different methods was 40-60%. One-hour and 24 hr posttransfusion corrected count increments (CCI) were compared as parameters for assessing success or failure of the transfusion. Using a rank scoring system, the relative efficiency of predictiveness for all transfusions was PRAT greater than LCT greater than PSIFT greater than ELISA. Combination of PRAT and LCT afforded the best predictability and sensitivity was higher than for either PRAT or LCT alone (93 vs. 79 and 62%, respectively). Mean posttransfusion CCI (x 10(9)/L) following PRAT-compatible platelets was 13.9 +/- 12.7 at 1 hr and 7.3 +/- 6.9 at 24 hr; following PRAT-incompatible platelets, 5.7 +/- 7.8 (1 hr) and 2.1 +/- 4.1 (24 hr). Results were similar for LCT-tested platelets. A radioimmunofiltration modification of the PRAT developed and used in selected cases was simple, fast, efficient, and inexpensive. The study indicated that the techniques evaluated are practical and feasible for routine use in the provision of compatible random donor platelets to the refractory patient who has no other cause for increased platelet destruction.

Adolescent↗
PubMed1988

Vasoconstrictor effects in spinal cord of the substance P antagonist [D-Arg, D-Trp7,9 Leu11]-substance P (Spantide) and somatostatin and interaction with thyrotropin releasing hormone.

The present study was undertaken to investigate the possible effects of Spantide [D-Arg1, D-Trp7,9 Leu11]-substance P, a substance P antagonist, and of somatostatin on spinal cord blood flow. The experiments were performed with the laser-doppler technique on the L1 spinal cord segment exposed by laminectomy. The effect of Spantide was also studied in the rat with the [14C]iodoantipyrine technique. In addition, experiments were performed on rabbit skeletal muscle in vivo after administration of Spantide to the local vasculature. In the experiments on spinal cord, approximately the same doses were employed as those earlier shown to be "neurotoxic". When the vehicle alone (0.9% saline) was administered intrathecally, a slight decrease of brief duration was noted in the blood flow. Spantide, however, caused a dose-dependent decrease, where 2 micrograms caused an immediate drop of the blood flow to approx. 20% of its normal value. A total circulatory arrest was found in several animals. In most cases, the flow was gradually normalized, whereas the effect persisted for up to 60 min in others. Virtually the same effect was exerted by somatostatin. The experiments using the iodoantipyrine technique confirmed the effect of Spantide. Here, the high resolution of this method showed that the gray matter was affected preferentially, with a complete ischemic state or a drastically reduced flow in 4 out of 5 animals 10 min after 2 micrograms of Spantide; one animal was unaffected, and this animal did not show any signs of motor impairment. The vasoconstriction of Spantide was not affected by simultaneous injections with substance P. However, after i.v. pretreatment with thyrotropin-releasing hormone, at a dose that previously has been reported to be protective against the neurodegenerative effects of Spantide, blood flow was markedly increased as compared to Spantide alone. Results from the experiments using intravital microscopy flow studies in the rabbit tenuissimus muscle revealed that Spantide at the doses used had no vasoconstrictor effect in the skeletal muscle of this species. The results suggest that previous demonstrations of motor impairment and "neurotoxic" actions of intrathecally injected substance P antagonists and somatostatin may be related to a marked decrease in spinal cord blood flow. Counteraction of the effect of Spantide by thyrotropin-releasing hormone may be explained by its effect to increase blood flow.

Animals↗
PubMed1988

Cavitating pneumonia caused by Corynebacterium group JK.

Corynebacterium group JK organisms were isolated from lung fluid aspirated with a fine needle from one of four thick-walled cavitary lesions in a 72-year-old female. Cultures and stains for mycobacteria and fungi were negative. The patient was successfully treated with an 8-week course of vancomycin.

Aged↗
PubMed1988

Epidural anesthesia in pregnant patients with low platelet counts.

A number of patients demonstrate thrombocytopenia in the peripartum period. One hundred four patients with unexplained transient periparturient thrombocytopenia were found over a nine-month period. Sixty-one of them received epidural anesthesia without neurologic sequelae. Epidural anesthesia is safe if the platelet count exceeds 100 x 10(9)/L in otherwise healthy women.

Anesthesia, Epidural↗
PubMed1987

Antinociceptive effects in mice after intrathecal injection of a substance P receptor antagonist, Spantide: lack of 'neurotoxic' action.

The present investigation was undertaken to determine the antinociceptive potency and possible neurotoxic effects of a substance P (SP) receptor antagonist, [D-Arg,D-Trp,Leu]SP (Spantide), after intrathecal injection in mice. After the nociceptive tests had been carried out, the animals were sacrificed and the spinal cords were investigated for histopathological changes, since such have been reported previously to occur in rats. It was found that the reaction latency in the tail-flick test increased in the dose range 0-10 micrograms. The effect was maximal at 10 and 45 min after 10 micrograms Spantide, and somewhat lower when 5 micrograms was used. None of the animals showed the complete motor impairment reported previously to occur after intrathecal administration in rats. In some of the mice we observed a slight rigidity in the hind-legs. At histopathological examination, it was found that Spantide produced no histological changes indicative of 'neurotoxic' effects. In agreement with this, the immunohistochemical evaluation, using calcitonin gene-related peptide (CGRP) as a marker for motoneurons and central branches of primary sensory neurons, did not provide evidence that the intrathecal injection of 10 micrograms Spantide produced any effects when compared to vehicle-injected animals. In conclusion, the present results demonstrate an antinociceptive effect of Spantide when injected intrathecally in mice, and that this occurred without any signs of toxic reactions in spinal cord as previously has been reported for the rat.

Analgesics↗
PubMed1987

Maturational changes in the pharmacological characteristics and actomyosin content of canine arterial and venous tissue.

The purpose of this study was to compare the pharmacological characteristics and actomyosin content of arterial and venous tissue at different times during development. Rings of arteries (femoral, renal, carotid, pulmonary) and veins (saphenous, pulmonary, jugular) were obtained from 1 wk, 1 month, and adult dogs, mounted at their optimal length for force development and the contractile response to potassium chloride and phenylephrine determined. The strain at optimal length was less at all ages in pulmonary artery and pulmonary and jugular veins than in other vessels. All vessels exhibited an increase in maximum contractile response with development but the increase was greater for phenylephrine. In general, the magnitude of the maximum response of the jugular and pulmonary veins and pulmonary artery was less than other vessels at all ages. The sensitivity (half maximum response) either increased or was unchanged in arteries with development, while in the veins it either decreased or was unchanged. The relaxant effects of verapamil and isoproterenol were determined on potassium chloride contracted vessels. Arterial tissue was minimally responsive to isoproterenol at all ages while venous tissue either increased its responsiveness (saphenous, pulmonary) with development or remained highly responsive (jugular). Verapamil, unlike isoproterenol, was an effective relaxant of all vessels. The actomyosin content (mg/mm) of femoral and renal arteries and saphenous and jugular veins increased with development but this increase was accompanied by a parallel increase in total protein so that the ratio (actomyosin/total protein) was unchanged. In jugular veins from adult dogs this ratio was smaller than in arterial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗