How effective is substance abuse treatment--compared to what?
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Alcoholism↗
Biomedical subjects
J Cornish
Publications and source records attributed to J Cornish.
A pilot trial of gepirone vs. placebo in the treatment of cocaine dependency.
An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (greater than 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addiction Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI.
Adult↗
Regulation of osteoblast proliferation by leukemia inhibitory factor.
We recently showed that leukemia inhibitory factor (LIF) stimulates 45Ca release from neonatal mouse calvariae in vitro and that it increases DNA and protein synthesis in this model. To elucidate further the actions of LIF on bone we now report the effects of this cytokine on DNA synthesis and cell proliferation in isolated fetal rat osteoblasts and in the osteogenic sarcoma cell line, UMR-106. In both actively growing and growth-arrested rat osteoblasts, LIF stimulated [3H]thymidine incorporation in a dose-dependent manner. The increase in DNA synthesis was time dependent, was associated with an increase in the number of osteoblasts, and was not blocked by indomethacin. LIF-treated cells showed reduced [3H]thymidine incorporation in comparison with control, as they approached confluence, possibly because of the increased cell density in the LIF-treated cultures. In UMR-106 cells, treatment with LIF inhibited [3H]thymidine incorporation in both actively growing and growth-arrested cultures. The effect was dose dependent and sustained with time. There was a corresponding decrease in cell numbers. It is concluded that although LIF causes an early stimulation of proliferation in isolated osteoblasts, it has opposing effects on UMR-106 cells. It is not possible to determine which of these effects is more relevant to the actions of LIF in vivo. The demonstration of a LIF effect on both these cell types, however, provides further evidence that this cytokine acts directly on osteoblasts.
Animals↗
Effects of leukemia inhibitory factor on bone resorption and DNA synthesis in neonatal mouse calvaria.
Leukemia inhibitory factor (LIF) is a recently characterized cytokine which has been shown to regulate cell growth and differentiation in a variety of tissues. We have shown that LIF stimulates bone resorption and DNA synthesis in bone organ culture and, in vivo, LIF has been shown to have marked effects on bone remodeling. The present study examines further the dose-response, time course and mechanisms of action of LIF in neonatal mouse calvaria. 45Ca release was significantly increased by LIF at concentrations of 10-5,000 U/ml, and its stimulation of bone resorption increased with time from 24 to 96 hours. These concentrations of LIF also increased DNA synthesis at 24 hours. At 72 hours, low concentrations of LIF produced less marked stimulation of [3H]-thymidine incorporation, and 5,000 u/ml actually inhibited DNA synthesis at both this time point and at 96 hours. The effect of LIF on 45Ca release was partially inhibited when DNA synthesis was blocked by hydroxyurea (50 microM). The resorptive effect of supramaximal concentrations of LIF was not additive to that of parathyroid hormone, 1,25-dihydroxyvitamin D3, prostaglandin E2, or transforming growth factor-beta. Although LIF-stimulated resorption is at least partially dependent on DNA synthesis, these results suggest that there are different mechanisms involved in mediating LIF's effects on bone resorption and DNA synthesis. The demonstration of effects of LIF at low concentrations indicates that this cytokine may be involved in the physiological regulation of bone metabolism in vivo.
Animals↗
Effective emetic control during conditioning of children for bone marrow transplantation using ondansetron, a 5-HT3 antagonist.
Preparation for bone marrow transplantation (BMT) uses the extremely emetogenic combination of chemotherapy and total body irradiation (TBI). Ondansetron is a selective 5-HT3 antagonist and has clear anti-emetic capabilities. The efficacy of the drug was assessed in 15 children (aged 2-17 years) who received high dose cyclophosphamide (on days -6 and -5) and TBI (days -3 to 0 inclusive). During days -6 to -4 when the emetic effect of cyclophosphamide would be most pronounced, 12 of the 15 patients (80%) had fewer than five emetic episodes during their worst 24-h period, 11 (73%) had fewer than three vomits whilst nine (60%) experienced no vomiting or retching. Eleven patients progressed to TBI and 10 (91%) had fewer than five emetic events in the worst 24-h period (days -3 to +2), six (55%) had no vomiting at all. Of 100 evaluable 'patient-days' 83 (83%) were without any vomiting or retching and a further 10 'patient-days' had only one or two emetic episodes. There were no significant side-effects noted and in particular no extrapyramidal reactions. Headaches and constipation, which have been seen in adult studies, were not reported by patient or parent on any of the study days and transient elevation of liver enzymes were noted in only two patients. Ondansetron has a major role in preparing patients for BMT.
Adolescent↗
Ultrastructural visualization of human bladder mucous.
Mucous within the urinary bladder appears to play a protective role in shielding the uroepithelium against pathogens. This present study employs specific anti-mucous, antisera stabilization techniques to visualize a thin, continuous layer of mucous closely adherent to the human bladder uroepithelium, in both scanning and transmission electron microscopic analyses.
Adult↗
Adenylate cyclase blockers dissociate PTH-stimulated bone resorption from cAMP production.
It is uncertain whether adenosine 3',5'-cyclic monophosphate (cAMP) or the inositol-calcium pathway mediates the stimulation of bone resorption by parathyroid hormone (PTH). Incubation of bone organ cultures with cAMP analogues and forskolin has not resolved this question because of the cellular inhomogeneity of bone and the consequent presence of adenylate cyclase-linked receptors for both PTH and calcitonin, hormones with opposite effects on bone resorption. We have used two new inhibitors of adenylate cyclase, 9-(tetrahydro-2-furyl)adenine (SQ 22536) and 2',5'-dideoxyadenosine (DDA), to directly reassess the role of cAMP in PTH-stimulated osteolysis. SQ 22536 (0.01-1.0 mM) and DDA (0.01-1.0 mM) completely blocked PTH stimulation of cAMP production measured in the absence of a phosphodiesterase blocker. In the presence of 1 mM 3-isobutyl-1-methylxanthine, half-maximal inhibition of PTH-induced cAMP production occurred with 0.2 mM SQ and 0.1 mM DDA, respectively. These concentrations of SQ and DDA had no effect on PTH-stimulated 45Ca release from calvaria, although both agents inhibited bone resorption when present at concentrations of 1-2 mM. At these levels, SQ and DDA caused equivalent inhibition of 45Ca release stimulated by 1,25-dihydroxyvitamin D3 but did not affect basal 45Ca release or [3H]-phenylalanine incorporation. It is concluded that substantial blockade of PTH-induced cAMP production does not affect this hormone's stimulation of bone resorption, which is therefore likely to be mediated by another intracellular messenger system, possibly calcium. In millimolar concentrations, SQ and DDA appear to be nonspecific blockers of osteoclastic bone resorption.
1-Methyl-3-isobutylxanthine↗
Leukemia inhibitory factor: a novel bone-active cytokine.
A number of cytokines have been found to be potent regulators of bone resorption and to share the properties originally attributed to osteoclast-activating factor. One such activity, differentiation-inducing factor (DIF, D-factor) from mouse spleen cells, shares a number of biological and biochemical properties with the recently characterized and cloned leukemia inhibitory factor (LIF). We have assessed the effects of recombinant LIF on bone resorption and other parameters in neonatal mouse calvaria. Both recombinant murine and human (h) LIFs stimulated 45Ca release from prelabeled calvaria in a dose-dependent manner. The increase in bone resorption was associated with an increase in the number of osteoclasts per mm2 bone. The osteolytic effect of hLIF were blocked by 10(-7) M indomethacin. hLIF also stimulated incorporation of [3H] thymidine into calvaria, but the dose-response relationship was distinct from that for bone resorption, and this effect was not blocked by indomethacin. Similarly, hLIF increased [3H]phenylalanine incorporation into calvaria, and this was also not inhibited by indomethacin. It is concluded that LIF stimulates bone resorption by a mechanism involving prostaglandin production, but that a distinct mechanism is responsible for its stimulation of DNA and protein synthesis. The primary structure of LIF differs from that of other fully characterized, bone-active cytokines, and it, thus, represents a novel factor which may be involved in the normal regulation of bone cell function.
Animals↗
Immunoregulation in Heymann nephritis. I. Cell marker studies.
Immunoregulation was examined in rats with Heymann nephritis (HN), an established model of membranous glomerulonephropathy (MGN). There is little known of the cellular immune events for the induction and maintenance of the autoimmune response in HN. The cell marker studies utilized fluorescein (FITC)-labelled monoclonal antibodies directed to B cells (Mark-I), and T cell subsets: pan T (ER-I), helper/inducer T (ER-2) and suppressor/cytotoxic T (ER-3). Lymphoid subsets were compared in spleen, lymph nodes, peripheral blood and bone marrow, of normal and diseased rats. Animals were investigated during the induction and chronic phases of disease. The induction of HN was associated with an early, significant, but transient increase of the non-specific myeloid component of the defence system. Subsequently, a significant increase was seen in the number of cells of the B lymphocyte lineage in HN animals, which coincided well with the overall increased humoral immune responsiveness. No alterations in the T lymphocyte subsets were noted during the development of this experimental autoimmune disease.
Animals↗
Naltrexone in federal probationers.
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Follow-Up Studies↗
Immunoregulation in Heymann nephritis. II. Functional studies.
In this study, the functional properties of the cells involved in the immunoregulation of Heymann nephritis (HN) have been investigated. HN is a disease model in the rat where the pathology closely resembles membranous glomerulonephropathy (MGN) in man. This autoimmune model is induced by injection of renal tubular antigen (RTA) incorporated in Freund's complete adjuvant (FCA). The strong B cell and plasma cell response in the chronic phase of HN, as determined by cell marker analyses, is predominantly antigen-non-specific. The secondary response pattern found was not only to RTA upon repeated immunization, but also to non-related antigen (SRBC). Although cell marker studies have indicated no major quantitative changes in the T cell population throughout the development of HN, a severe deregulation of the cellular immune response is observed especially during the induction period of HN. This was shown by a strong decrease of the mitogen-induced proliferative response and IL-2 production. This phenomenon is caused by both defective cellular components and inhibitory serological factors. Finally, in the chronic phase, these aberrations gradually return to normal.
Animals↗
Reliable diagnosis of Trichosomoides crassicauda in the urinary bladder of the rat.
Two reliable methods are described for identifying infection of laboratory rats with the nematode Trichosomoides crassicauda. The first is a rapid method where cryostat sections of the rat urinary bladder are stained with acridine orange and viewed under a fluorescence microscope. The second involves the stabilization of the bladder surface prior to examination using scanning electron microscopy (SEM).
Animals↗
Host defence mechanisms in the bladder. II. Disruption of the layer of mucus.
The urinary bladder wall is lined by a layer of mucus which is believed to provide an important barrier to bacterial invasion of the urinary tract. Abnormal function of this protective layer could therefore be a factor predisposing the host to urinary tract infection (UTI). This study investigated the contribution of the bladder mucus to host defence in both acute and chronic lower UTI, using a non-obstructive animal model of infection which reproduces many features of the disease in man. The ultrastructural appearance of the infected bladder mucosa was assessed in tissue in which both the layer of mucus and bacterial glycocalyces were stabilized prior to examination by scanning and transmission electron microscopy. The protective role of the mucus layer was determined by disrupting the layer immediately prior to bacterial challenge. Both ultrastructural and bacteriological analyses have shown that infection was increased in those animals where the mucus barrier was disrupted.
Animals↗
Significance of cyclosporin-A-associated renal surface irregularities.
The purpose of this study was to investigate unusual irregularities observed on the surface of kidneys from rats which had been treated with seven 'clinically effective doses' (25 or 50 mg/kg) of cyclosporin A (CsA). Surface corrugations were obvious on gross examination and were a universal finding in our study which involved greater than 50 rats. Examination by scanning electron microscopy (SEM) showed that the surface irregularities resulted from swollen peritubular capillaries adjacent to vacuolized and partially collapsed tubules at the cortical surface. The enlarged capillaries were associated with vascular congestion, and although peritubular capillary congestion has been recognized in CsA-treated patients, it has been difficult to determine whether this reaction is associated with drug toxicity or graft rejection. Our findings, indicating that peritubular capillary congestion in addition to vacuolization and collapse of subcapsular tubules is a drug-associated phenomenon, may help give a more accurate assessment of biopsy and autopsy material from CsA-treated patients and laboratory animals.
Animals↗
Host defence mechanisms in the bladder. I. Role of mechanical factors.
This study evaluated the contribution of host defence mechanisms to bacterial clearance from the urinary bladder using an animal model in which rats were infected with Escherichia coli. Factors studied included the effect of hydration status, induced ultrastructural changes to the surface of the bladder mucosa, and the relevance of bacterial replication. Clearance was divided into two phases, primary (0-4 h), and secondary (4-24 h). Ninety-nine per cent of Escherichia coli 075 was cleared during the primary phase from normal, dehydrated and polyuric animals and 93% from anuric animals. Clearance was shown to be dependent on the presence of viable tissue. Bacterial numbers continued to decrease during the secondary phase in normal and dehydrated animals but increased in polyuric and anuric groups. No such rise occurred when rats were inoculated with Escherichia coli E/2/64, a non-replicating mutant. Evidence of ultrastructural changes to the bladder associated with impaired antibacterial properties was found in polyuric and anuric animals. Clearance of particulate matter (killed Candida albicans) however was unaffected by mucus disruption. The study has shown that the clearance of microorganisms from the bladder was unrelated to the voided volume, but is closely associated with the antibacterial activity of the mucosal surface.
Animals↗
An animal model for chronic infection of the unobstructed urinary tract.
Chronic cystitis due to Escherichia coli is frequently associated with anatomical or functional abnormalities of the lower urinary tract, but there is no satisfactory animal model available to help resolve biological and management problems. We have induced chronic infection of the unobstructed urinary tract in the rat by implanting a small polyurethane sponge into the dome of the bladder, 14 days before bacterial challenge. This manipulation provides a focus of infected urine and leads to the establishment of a chronic cystitis. Both the predisposing factor and the pathological details mimic important features of the disease in man.
Animals↗
Mucus stabilization in the urinary bladder.
Mucus in the urinary bladder may act as an important intrinsic defence mechanism by shielding the epithelial layer from pathogens. Visualization of any such layer of mucus using electron microscopy has not been possible, as preparative procedures in current use result in the loss or distortion of mucus. We evaluated methods reported to stabilize polysaccharide layers and demonstrated that pretreatment of rat bladder tissue with anti-mucus antiserum, minimized the collapse of the mucus that normally occurred during dehydration of the tissue for electron microscopic examination. Under these conditions, mucus was stabilized as a layer closely adherent to the epithelium.
Animals↗
Mucosal mast cells as a component of the inflammatory response to lower-urinary tract infection.
Globule cells have been observed in mucosae for many years. Recently, a subpopulation of these globule cells in the intestinal mucosa of man and rodents have been identified as unique mast cells. In this communication, intraepithelial globule cells and some lamina-propria mast cells found in the normal rat urinary-bladder wall have been characterized as mucosal mast cells, similar to intestinal mast cells, and differentiated morphologically and histochemically from rat peritoneal mast cells. The number of mast cells in the bladder wall increased significantly during various bladder manipulations, including mechanical trauma, parasitic infestation and bacterial infection. The origin and function of the mucosal mast cells remains unknown.
Animals↗