PubMed Health⌕ Search

Biomedical subjects

C Conover

Publications and source records attributed to C Conover.

At least 19 recordsLinked to original sources

Improving health outcomes among individuals with HIV, mental illness, and substance use disorders in the Southeast.

Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants' psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings.

Adult↗

Does distance affect utilization of substance abuse and mental health services in the presence of transportation services?

Long travel times have been identified as a significant barrier to accessing mental health and other critical services. This study examines whether distance to treatment was a barrier to receiving outpatient mental health and substance abuse care for HIV-positive persons when transportation was provided. Data from a cohort of HIV-positive persons who participated in a year-long substance abuse and mental health treatment programme were examined longitudinally. Transportation, which included buses, taxis, and mileage reimbursement for private transportation, was provided free of charge for participants who needed this assistance. Nearly three-quarters (74%) of participants utilized the transportation services. No statistically significant differences in retention in, or utilization of, the mental health and substance abuse treatment programme were identified by distance to the treatment site. This analysis demonstrated that increased distance to care did not decrease utilization of the treatment programme when transportation was provided to the client when necessary. These results provide preliminary evidence that distance to substance abuse and mental health services need not be a barrier to care for HIV-positive individuals when transportation is provided. Such options may need to be considered when trying to treat geographically dispersed individuals so that efficiencies in treatment can be attained.

Adult↗

Effects of asthma on cell components in peripheral blood among smokers and non-smokers.

BACKGROUND: Eosinophils play a central role in asthma, but the interplay of the effects of smoking, eosinophils and asthma remains unclear. OBJECTIVE: The primary objective of our study was to investigate the extent to which smoking modifies the effect of asthma on circulating eosinophils, CD4+ and CD8+ T cell counts. METHODS: Data were collected semiannually between 1987 and 1994 from HIV-negative participants in the Multicenter AIDS Cohort Study. Asthma was defined by a questionnaire at baseline as a self-report of diagnosed asthma. A total of 1420 blood samples from 197 asthmatics and 15 822 from 1997 non-asthmatics were collected. RESULTS: Eosinophil levels were higher in asthmatics (28% of asthmatics had eosinophils >/=4% and 16% of non-asthmatics) regardless of smoking history, but smoking modified the association between eosinophils and asthma. Namely, the odds ratios for eosinophils being >/=4% in asthmatics to non-asthmatics decreased from 2.7 (95% CI: 2.0, 3.6) in never, to 2.1 (1.4, 3.1) in former, and to 1.5 (0.9, 2.3) in current smokers. Cross-sectional and longitudinal analyses coherently showed that smoking increased eosinophils in non-asthmatics, but the converse was true for asthmatics. In contrast, no differences in peripheral blood T cell counts between asthmatics and non-asthmatics were observed. CONCLUSION: Under the established link between increased eosinophils and asthma, these data indicate that smoking modified this relationship. This finding suggests that smoking plays a different immunological role in asthmatics and non-asthmatics.

Adult↗

Outbreak of multidrug-resistant tuberculosis at a methadone treatment program.

SETTING: An out-patient methadone treatment program MTP). OBJECTIVE: To investigate transmission of multidrug-resistant tuberculosis (MDR-TB) in the MTP. DESIGN: Cases were defined as MTP clients or staff who developed TB between 1 January 1994 and 1 January 1996, with at least one positive culture for Mycobacterium tuberculosis resistant to isoniazid and rifampin. Contacts were identified, located and evaluated. RESULTS: Thirteen cases of MDR-TB occurred among 462 clients and staff. One fifth (6/30) of the members of a counseling group for human immunodeficiency virus (HIV) infected clients developed MDR-TB. Individuals known to be HIV positive were at greater risk for TB than those who were HIV negative (RR 5.2, 95%CI 1.2-22.7). Of 449 clients and staff identified as contacts, 393 (87.5%) were located and screened. Among those with a negative baseline tuberculin skin test, 18.5% (56/303) were skin test converters. Attendance at the MTP during a period when the index case was infectious was associated with an increased risk of conversion (RR 2.5, 95%CI 1.1-6.0). CONCLUSION: Extensive transmission of MDR-TB occurred at an out-patient MTP serving numerous clients with HIV infection. This outbreak underscores the importance of developing effective strategies to prevent TB transmission in this setting.

Adult↗

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact.

FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identified putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in different tumors. Using a high density of PCR amplifiable markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply reflect instability of the FRA3B region during tumor progression.

Carcinoma, Renal Cell↗

Single-chain Fv with manifold N-glycans as bifunctional scaffolds for immunomolecules.

Unlike natural antibodies, single-chain Fv (sFv) proteins normally lack asparagine-linked glycosylation. Many designed immunoconjugates and other therapeutics currently employ the advantageous conjugation chemistry or targeting properties provided by the glycoprotein oligosaccharide domain. sFv proteins with engineered N-glycan designs were evaluated in Pichia pastoris for glycosylation efficiency, expression level, oligosaccharide chain length and composition, and affinity. In contrast to nearly all natural glycoproteins, the engineered attachment of N-glycans conveniently near the polypeptide C-terminus was found to produce the optimal results. Furthermore, the percentage modification and chain length of the attached mannose chains were controllable by the use of tandem and overlapping Asn-X-Thr tripeptide sites. The glycosylated sFv mannose chains could be effectively conjugated to polyethylene glycol and the resulting conjugate displayed a 10-fold increased circulating life in mice. The potential to control polymer:sFv or drug:sFv molar ratios by site-specific conjugation may substantially improve the therapeutic efficacy of these minimal antigen-binding molecules.

Animals↗

Evaluation of the oxygen delivery ability of PEG-hemoglobin in Sprague-Dawley rats during hemodilution.

Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its oxygen delivery capability while increasing its plasma expansion capacity. To determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery capability rather than its plasma expansion capacity, Sprague-Dawley rats were exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%-methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats surviving 14 days were evaluated for hematology, blood chemistry and histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived the 2 week observation period had normal hematological and blood chemistry levels and no significant morphological effects. Therefore, this study demonstrates that PEG-Hb can sustain life while similar plasma expansion agents with less oxygen delivery capability are not as effective.

Animals↗

Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat.

This study was designed to assess the morphological effects of a bolus infusion of PEG-hemoglobin on the heart, lung, liver, spleen and kidney of laboratory rats. Of particular interest was the determination of PEG-hemoglobin's potential to form vacuoles in the tissues and whether these were transitory and article specific. One hundred ten female Sprague-Dawley rats were used in this study. The first experiment determined whether vacuole formation was test article specific by infusing either stroma-free bovine hemoglobin, PEG-hemoglobin, bovine serum albumin, PEG-bovine serum albumin or free PEG. The second experiment assessed the transitory nature of vacuolization. In both experiments, unconscious rats received an intravenous top-loading (bolus) injection of test article via the tail vein. Rats were sacrificed at various time points following administration and had their tissues examined for the presence of vacuoles by light microscope morphological examination and iron staining. Formation of vacuoles appeared to be test article specific with only prolonged circulating, high solute test articles producing vacuoles. These vacuoles appeared dose responsive and transitory in nature. The vacuolization found was non-toxic and believed to be due to the known effect of lysosomal overloading following the phagocytosis of vascularly persistent high solute test articles.

Animals↗

Serial long-term assessment of in vivo LHRH release from a discrete area of the ewe median eminence using multiple guide cannula assembly and removable push-pull cannulae.

Analysis of neuronal interactions at the median eminence (ME) that control anterior pituitary function requires sampling of in vivo release of specific hypophysiotropic components and of putative inputs that might regulate such a release. We developed a multiple guide cannula assembly (MGCA) to sample repetitively discrete areas of the ewe ME, using removable push-pull cannula (PPC) probes. The MGCA is attached to the skull over the ME using stereotaxic surgery. A specific guide cannula of the assembly (1 of 48 guides) located on the midline and directly on top of the central portion of the ME is selected based on roentgenograms obtained after infusion of radiopaque contrast material into the third ventricle. The MGCA and the large size of the ewe brain allows the simultaneous positioning of a PPC probe, an infusion cannula or another removable probe in additional discrete hypothalamic and extrahypothalamic areas. To determine the capabilities of this sampling technique, we assessed in vivo release of LHRH from the extracellular space at the posterior-lateral ME, under various reproductive conditions that have well-defined LH-secretory patterns. The pulsatile profile of both LHRH and LH was significantly lower in anestrus than during the follicular phase of cycling ewes. In vivo pulsatile release of LHRH was higher in the follicular than in the midluteal phase of ewes sampled repetitively from the same ME site during three consecutive estrous cycles. All ewes showed increased midluteal progesterone levels. In vivo LHRH release, as determined by PPC sampling of the extracellular fluid at the posterior-lateral ME, probably reflects a mix of hypophysiotropic and nonhypophysiotropic LHRH components. Histological analysis revealed a well-organized, pallisade-like array of astroglial processes along the track of chronically implanted cannulae. This glial scar is disrupted along the tracks of acutely reimplanted cannulae but without apparent difference in the yield of the method. Our method increases the efficiency and versatility of ME PPC sampling providing an additional tool to assess the role of the ME as the final neuroendocrine control site of anterior pituitary function.

Animals↗

Normal somatomedin-C/insulin-like growth factor I binding and action in cultured human fibroblasts from Turner syndrome.

Growth retardation is a major manifestation of Turner syndrome (TS). Since plasma growth hormone and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) levels are generally normal, growth failure has been ascribed to peripheral defects in SM-C/IGF-I receptors or action. We have measured the binding of [125I]SM-C/IGF-I to cultured fibroblast monolayers derived from patients with Turner syndrome, and have evaluated SM-C/IGF-I stimulation of both [3H]thymidine incorporation and cell replication. When compared to fibroblasts from normal adults, newborns, and age-matched children, no significant differences were observed in specific binding of [125I]SM-C/IGF-I to fibroblast monolayers, and displacement curves demonstrated similar receptor affinities for all groups. Similarly, equivalent SM-C/IGF-I stimulation of [3H]thymidine incorporation was seen in both Turner and control fibroblasts. In the absence of serum, SM-C/IGF-I, at a concentration of 10-25 ng/ml, stimulated thymidine incorporation 3.7-11.8-fold in Turner fibroblasts and 1.9-9.8-fold in control cells. In combination with 1.0% human hypopituitary serum (HHS), SM-C/IGF-I stimulated thymidine incorporation 20-70-fold in all cell lines. Cell replication in both TS and control cells was increased 90% by the combination of SM-C/IGF-I + 0.5% HHS, and 140% by SM-C/IGF-I + 0.5% HHS + dexamethasone. We conclude that TS fibroblasts have normal SM-C/IGF-I receptors and sensitivity, and are capable of enhanced DNA synthesis and replication following SM-C/IGF-I stimulation.

Adult↗

Partial characterization of an insulin-dependent serum factor that regulates ornithine decarboxylase in skeletal muscle.

We have previously shown that a factor(s) in rat serum induces ornithine decarboxylase (ODC) in incubated muscle and that its activity is diminished in sera from diabetic rats. To characterize this factor further, we have studied some of its physicochemical and biologic properties. As judged from its ability to induce ODC in the incubated rat soleus muscle, the factor is protease-sensitive and both heat- and acid-stable. In untreated whole serum its activity is associated with a high-molecular-weight fraction whereas after boiling at pH 5.5, activity is principally in a fraction with a molecular weight between 3500 and 12,000 daltons. The activity of the factor is diminished in hypophysectomized, starved, and aged as well as diabetic rats. In diabetic rat serum it is restored to normal by the addition of a purified somatomedin, multiplication-stimulating activity. These findings suggest that the "ODC inducing factor" is a low-molecular-weight peptide and that it has many of the characteristics of a somatomedin.

Animals↗

Effects of aliphatic diamines on rat liver ornithine decarboxylase activity.

Rat liver ornithine decarboxylase activity was decreased by administration of putrescine (1,4-diaminobutane) or other diamines, including 1,3-diaminopropane, 1,5-diaminopentane and 1,6-diaminohexane. This effect was seen in control rats and in rats in which hepatic ornithine decarboxylase activity had been increased by administration of growth hormone (somatotropin) or thioacetamide. Loss of activity was not dependent on the conversion of putrescine into polyamines and was short-lived. Within 6h after intraperitoneal administration of 0.8 mmol/kg body wt., ornithine decarboxylase activity had returned to normal values. This return correlated with the rapid loss of the diamines from the liver, and the decrease in activity could be slightly prolonged by treatment with aminoguanidine, a diamine oxidase inhibitor. A decrease in ornithine decarboxylase activity by these diamines was accompanied by the accumulation in the liver of a nondiffusible inhibitor that decreased the activity of a purified ornithine decarboxylase preparation. The possibility that administration of non-physiological diamines that are not converted into polyamines might be useful for the inhibition of polyamine synthesis is discussed.

Animals↗

Effect of insulin on kinetics of sugar transport in heart muscle.

Insulin increased the maximal rate of sugar transport in the perfused rat heart, but had essentially no effect on the Michaelis constant of sugar entry or half-maximal constant for equilibrium exchange. In control hearts, the following kinetic parameters of 3-O-methylglucose transport were measured: Michaelis constant for entry, 7-10 mM; equilibrium exchange constant, 7 mM; and activity constant (Vmax/Km) from 0.02 to 0.1 ml/g.min. In insulin-treated hearts, these values were 6 mM, 3 MM, and 2.2 ml/g.min, respectively. These changes in transport constants were consistent with a model in which 1) sequestered carrier was released by the hormone or 2) carrier movement, in all forms and directions, was accelerated. Measurements of glucose transport in control hearts indicated that the Michaelis constant for entry was 4 mM and the activity constant, 0.5 ml/g.min. In insulin-treated hearts, quantitation of transport parameters was prevented by accumulation of intracellular glucose.

Animals↗