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Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 127 records · Page 7Linked to original sources
PubMed1995

A randomized evaluation of consumer versus nonconsumer training of state mental health service providers.

Preliminary evidence suggests that mental health consumers can successfully serve as peer companions, case management aides, case managers, job coaches, and drop-in center staff. However, few empirical investigations have addressed the use of consumers to train mental health professionals. This project employed a randomized design to test the effects of using consumers as trainers for mental health service providers. Fifty-seven state mental health professionals participated in a two-day training designed to acquaint trainees with the attitudes and knowledge necessary for delivering assertive case management services. Participants were randomly assigned to one of two conditions: one in which they received the second day of training from a consumer and the other involving training by a nonconsumer. Analyses revealed that post-training attitudes were significantly more positive for those participants trained by the consumer. Subjective evaluations also reflected positive reactions to the use of consumers as trainers. Implications for further use of mental health consumers as trainers are explored.

Adult↗
PubMed1995

Nitric oxide (NO) protects against cellular damage by reactive oxygen species.

Since the discovery of nitric oxide (NO) as an endogenously formed radical, its effect on numerous physiological processes has been intensively investigated. Some studies have suggested NO to be cytotoxic while others have demonstrated it protective under various biological conditions. Though NO shows minimal cytotoxicity to a variety mammalian cell cultures, it does modulate the toxicity of some agents such as reactive oxygen species. Often, NO is generated in the presence of these reactive oxygen species in response to foreign pathogens or under various pathophysiological conditions. We will show that NO can play a protective role under oxidative stress resulting from superoxide, hydrogen peroxide and alkyl peroxides. It was found by measuring the time-concentration profiles of NO released from various NO donor compounds that only microM levels of NO were required for protection against the toxicity of these reactive species. It was found that there are several chemical reactions which may account for these protective effects such as NO preventing heme oxidation, inhibition of Fenton-type oxidation of DNA, and abatement of lipid peroxidation. Taken together, NO at low concentrations clearly protects against peroxide-mediated toxicity.

Animals↗
PubMed1995

Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells.

We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.

Animals↗
PubMed1995

The effect of nasal mucosal vasoconstriction on nasal airflow sensation.

The correlation between the objective measurement of nasal resistance and nasal airflow sensation is usually regarded as poor. To investigate the relationship between these two parameters 20 healthy volunteers had nasal resistance to airflow measured by rhinomanometry compared with nasal sensation by visual analogue scoring before and after nasal mucosal vasoconstriction using topical 0.1% xylometazoline. The median change in nasal resistance was 0.2 kPal-1s (95% CI 0.08-0.28 kPal-1s) and in nasal sensation 24 mm (95% CI 17 mm-35 mm). A significant relationship between nasal sensation and nasal resistance to airflow was found (Kendall's Rank correlation (P < 0.05). This function can be described by the linear regression equation: dS = 13.2 + 70.dNR where dS = change in nasal sensation and dNR = change in nasal resistance. There may be a much closer relationship between subjective and objective measures of nasal patency than has previously been thought.

Adult↗
PubMed1995

Lymphoma presenting to a head and neck clinic.

Lymphomas generally have a good prognosis compared with squamous carcinomas. The present study investigates a series of 185 lymphomas of the head and neck seen over a 30-year-period. The records of 236 patients were examined and the histology slides reviewed. The lymphomas were classified according to the working formulation method and staged using the Ann Arbor system. A total of 185 patients had a non-Hodgkin's lymphoma, of those 43 were low grade, nine intermediate and 103 high grade. The histology slides of 30 patients were not available for review. In addition, 51 patients had Hodgkin's disease. One hundred and fifty patients were stage 1 or 2 and 74 stage 3 or 4. In 12 patients insufficient data was available for staging; 152 were extranodal and 84 nodal. The 5-year survival of those patients with Hodgkin's disease was 73%. For the patients with non-Hodgkin's lymphoma the 5-year survival was 43% for low grade and 48% for high grade lesions. The survival of patients with Hodgkin's disease was significantly better than for non-Hodgkin's lymphoma (P < 0.01). The 5-year survival of patients with extranodal disease was 54% and for patients with nodal disease 65% (P = NS). Treatment was by irradiation for localized lesions and by chemotherapy or a combination for more advanced lesions. Lymphomas have a relatively good prognosis in the head and neck as elsewhere in the body and every effort should be made to provide adequate diagnosis and treatment in combined clinics.

Aged↗
PubMed1995

The nasal response to isometric exercise.

The cardiovascular response to isometric exercise is well understood. However, the response of the nasal mucosa is less well known. We have attempted to document this response in normal individuals. Ten individuals with no history of nasal disease or allergy were studied. All subjects were asked to perform sustained handgrip on the side of the obstructed nostril for a period of 5 min at 30% of maximum voluntary effort. Nasal cross-sectional area was measured on both sides of the nose using an acoustic rhinometer. The individuals were then rested for at least 30 min and the test repeated with pressure applied by the opposite hand. Statistical analysis was performed by non-parametric methods. There was a significant fall in nasal cross-sectional area on the side of exercise median change = 0.09 cm2, P < 0.01) while cross-sectional area in the contralateral nasal passage increased (median change = 0.35 cm2, P = 0.01). There was no significant differences between these results and those obtained by handgrip on the opposite side. The results indicate that isometric exercise produces nasal obstruction (isotonic exercise) and both afferent and efferent arms of this reflex are side-specific.

Blood Pressure↗
PubMed1995

Quantifying the Carhart effect in otosclerosis.

The Carhart effect consists of a depression in bone conduction thresholds in the presence of a conductive hearing loss. However, the mathematical relationship between the degree of conductive hearing loss and the degree of depression of bone conduction has not before been described. We have reviewed pre- and post-operative pure-tone audiograms performed on 102 consecutive patients having stapedectomy in an attempt to identify relationships between changes in bone conduction and air conduction and air-bone gap closure. Significant linear relationships were found between bone conduction and air conduction at 0.5. 1, 2 & kHz. Bone conduction was linearly related to air bone gap closure at 2 kHz.

Adolescent↗
PubMed1995

Limitations of acoustic rhinometry determined by a simple model.

To determine the accuracy of a commercially available transient signal acoustic rhinometer we constructed simple models from tubing of known dimensions. A series of models was constructed in which the main cylinder was constant whilst the aperture of an included constricted area was varied from 0.07 cm2-0.95 cm2. The area reconstruction for each model was then compared with the true area. Two parameters based on those used in clinical practice of acoustic rhinometry were employed to evaluate the error. The results demonstrate that the measurement of both the volume beyond a constriction and the area of the constriction may be associated with systematic errors. The reconstructed profile of each model is similarly erroneous. As the nose presents a proximal constriction, these findings are of considerable relevance to the clinical use of acoustic rhinometry.

Acoustics↗
PubMed1995

Perseverative errors and reversal of a visual discrimination following basal forebrain lesions in the rat.

Rats with electrolytic lesions of the nucleus basalis magnocellularis were compared to sham-lesioned rats in the retention of a continuously reinforced lever-pressing response and in the acquisition and reversal of a visual discrimination task. The muscarinic agonist pilocarpine, in conjunction with the peripheral muscarinic antagonist methyl-scopolamine, was administered in three doses to subsets of each group during acquisition. The lesion interfered with retention of the lever-pressing response. It did not affect the rate of acquisition of the visual discrimination, but facilitated reversal, and increased the number of perseverative errors made by the rats. Pilocarpine's only notable effect was to increase the latency to respond.

Animals↗
PubMed1995

Medical sociology and the study of severe mental illness: reflections on past accomplishments and directions for future research.

Over the past 40 years, the mental health care system has been radically transformed from one focused on institutionalized care to one centered on treatment in community settings. While medical sociology has played a prominent role in the study of psychiatric hospitalization and the deinstitutionalization process, the systematic exploration of the sociological dimensions of community-based mental health care is only just beginning. This essay reflects on past disciplinary contributions and explores some important empirical and theoretical directions in the field of mental illness research that could benefit from more extensive sociological analysis. The central argument is that the shift to a community-based mental health system has increased the need for the sociological perspective and that medical sociologists, in particular, have the theoretical and analytical perspective essential for developing a more complete understanding of the current conditions impacting the lives of people with severe mental disorders. Drawing on recent work in medical sociology, we illustrate some important topical areas at the center of controversies over treatment, social change, and public policy regarding severe mental illness. We conclude with a discussion of the barriers to this type of sociological research and suggestions for ways medical sociologists might contribute to the study of severe mental disorders in the future.

Deinstitutionalization↗
PubMed1995

Increased nitric oxide synthesis during the development of endotoxin tolerance.

The role of nitric oxide (NO) synthesis was investigated in endotoxin (LPS) tolerance induced in rats by intraperitoneal injection of a sublethal dose of Salmonella enteritidis LPS (100 micrograms/kg intraperitoneally). Peritoneal macrophages were harvested 6 and 24 h after LPS injection and stimulated in vitro with LPS. LPS significantly stimulated arachidonic acid metabolism, as assessed by 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels, and NO production, as assessed by nitrite, in macrophages collected from control rats. In macrophages from tolerant rats LPS-stimulated 6-keto-PGF1 alpha production was significantly reduced, while nitrite production was increased compared to control macrophages (p < .001). In in vivo mortality studies, rats that were pretreated 24 h earlier with sublethal LPS were resistant to the lethal effect of a subsequent dose of LPS (15 mg/kg intravenously) in comparison to control rats (p < .001). NG-Nitro-L-arginine-methyl ester, an inhibitor of NO synthase, decreased mean survival time in control rats and abrogated the resistance to the lethal effect of LPS in tolerant rats. In contrast, molsidomine, a NO donor, improved survival in control rats but did not modify the resistance to the lethal dose of LPS in tolerant rats. The results suggest that sustained NO synthesis may be a beneficial mechanism for the induction of LPS tolerance.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Reorientation of macrophage mediator production in endotoxin tolerance.

During endotoxin shock macrophages produce arachidonic acid (AA) metabolites, nitric oxide (NO) and interleukin 6 (IL-6). In contrast, macrophages from endotoxin tolerant rats become hyporesponsive to LPS-induced AA metabolites production. However the role of NO and IL-6 during endotoxin tolerance is not known. Therefore, we evaluated the production of the AA metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), IL-6 and NO (by nitrite measurement) by peritoneal macrophages from endotoxin tolerant rats. Since pertussis toxin (PT) sensitive guanine nucleotide binding regulatory (Gi) protein activity is altered during endotoxin tolerance, we also studied the effect of PT on the regulation of the above mediators synthesis. Endotoxin tolerance was induced in rats by intraperitoneal injection of a sublethal dose of Salmonella enteritidis lipopolysaccharide (LPS, 100 micrograms/kg ip). Peritoneal macrophages were harvested 24 hours after LPS injection and stimulated in vitro with LPS (50 micrograms/ml) for determination of NO activity by nitrite, 6-keto-PGF1 alpha and IL-6 production. In macrophages collected from vehicle-pretreated rats (control) LPS stimulates all three mediators. In vivo pretreatment with LPS induced a desensitization of macrophages to LPS-induced 6-keto-PGF1 alpha production compared to control macrophages (p < 0.001). LPS-stimulated IL-6 synthesis was also partially, but not completely, reduced in tolerant macrophages (p < 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Age-related mortality and adherent splenic cell mediator production to endotoxin in the rat.

Rat neonatal mortality to endotoxin and age-related changes in adherent splenic cell mediator production in vitro were investigated. Neonatal rat pups, 24, 48, 96, and 216 h old or maternal adult rats were administered doses of Salmonella enteritidis endotoxin, (.024 mg to 7.5 mg/kg) and survival was monitored for 72 h. Mortality demonstrated high sensitivity (p < .05) of neonates to endotoxin (particularly 24 h old neonates). Endotoxin administration .6 mg/kg intracardiac) produced a 100% lethality in 24 h neonates (p < .05) versus 23% or less lethality in the 48 to 216 h old age group. Endotoxin administration (.4 mg/kg subcutaneous) also produced 100% lethality in 24 h old neonates compared with reduced mortality versus older age groups. Endotoxin in vitro stimulated (p < .05) adherent splenic cell thromboxane (TX)B2, interleukin-6, and nitrite production in most groups. Splenic cell nitrite production was higher (p > .05) in the 24 h old neonates, but lower in 48 h and 96 h old groups compared with maternal adults. Splenic cell TXB2 production was higher (p < .05) in the 24 h and 216 h old neonates relative to maternal adults. In conclusion, 24 h old rat pups are more susceptible to endotoxic shock than older age groups and adults, and exhibit altered production of the cellular mediators nitric oxide and TXB2.

Aging↗
PubMed1995

Radiodetoxified endotoxin-induced tolerance. Effect on endotoxin lethality and macrophage arachidonic acid metabolism.

Endotoxin (LPS) tolerance produces changes in macrophage mediator production which is thought to be responsible for the acquired LPS resistance. Detoxification of LPS by gamma irradiation has been reported to diminish certain noxious properties while retaining its tolerance inducing actions. We compared the efficacy of LPS and radiodetoxified (RD)-LPS from Escherichia coli O101 on stimulating rat peritoneal macrophage arachidonic acid (AA) metabolism, measured by thromboxane (TXB2). Changes in macrophage production of these mediators were also assessed after tolerance induction. LPS tolerance was induced by i.p. injection of LPS, RD-LPS or vehicle on day 1 (100 micrograms/kg, i.p.) and day 2 (500 micrograms/kg, i.p.). On day 5 or 4 weeks after pretreatment, peritoneal macrophages were harvested for in vitro studies, or rats were tested for lethality resistance. Macrophages were incubated +/- LPS (0.1 ng to 50 micrograms/ml), lipid A (1 or 10 micrograms/ml) or Ca+2 ionophore A23187 (10 microM) for determination of TXB2 production. Minimum effective concentrations of LPS and RD-LPS for stimulation (P < 0.05) of TXB2 were 100 ng/ml and 1 microgram/ml, respectively. Maximal stimulation of TXB2 occurred at 10 micrograms/ml of LPS or RD-LPS. Macrophages from LPS or RD-LPS tolerized rats were refractory to stimulated TXB2 with LPS or RD-LPS (0.1 ng to 50 micrograms/ml). The suppressed in vitro macrophage TXB2 production was apparent 4 weeks after rats were tolerized with LPS or RD-LPS. In subsequent mortality studies, LPS challenge of control or tolerance rats at day 5 in vivo with Salmonella enteritidis LPS (15 mg/kg, i.v.) produced a 90% mortality in control rats (N = 22), versus 13% mortality in the LPS pretreated group (N = 23) and a 20% in the RD-LPS pretreated group (N = 10) (P < 0.05 vs control). However, this lethality resistance was not apparent at 4 weeks after LPS or RD-LPS pretreatment. Both LPS and RD-LPS appear to be equipotent in inducing macrophage alterations, and in lethality resistance during LPS tolerance induction. However, these observations suggest that during LPS tolerance suppression of LPS-stimulated AA in peritoneal macrophage metabolism persists longer than acquired lethality resistance.

Animals↗
PubMed1994

Treatment of locally advanced cancer of the head and neck with 5'-iododeoxyuridine and hyperfractionated radiation therapy: measurement of cell labeling and thymidine replacement.

BACKGROUND: The halogenated pyrimidines 5'-iododeoxyuridine (IdUrd) and 5'-bromodeoxyuridine (BrdUrd) are under active study as radiation sensitizers for a variety of malignancies. Head and neck neoplasms may also be suitable for halogenated pyrimidine-mediated sensitization; previous regimens using intra-arterial BrdUrd delivery, however, were poorly tolerated. PURPOSE: A pilot study was undertaken with the use of intravenous IdUrd with hyperfractionated radiotherapy to assess tolerance. In addition, serial tumor biopsy specimens were obtained to determine the kinetics of IdUrd labeling and incorporation. METHODS: Twelve patients with squamous cell carcinomas of the head and neck (one patient had stage II cancer, one had stage III, and 10 had stage IV) were treated with hyperfractionated radiation therapy at a dose of 1.2 or 1.5 Gy twice a day, to a total dose in the range of 70-76 Gy. IdUrd (1000 mg/m2 per day) was infused for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. A tumor biopsy specimen was obtained from 11 patients following initiation of treatment with IdUrd. Eight patients consented to serial biopsy to allow the study of IdUrd-labeling indices and thymidine replacement over time. Incorporation of IdUrd into tumor DNA was determined by high-performance liquid chromatography, and cell labeling was determined with the use of an anti-BrdUrd/IdUrd monoclonal antibody in conjunction with flow cytometry. Patients continue to be followed to assess local control. RESULTS: A plot of corrected IdUrd replacement as a function of infusion time suggests the possibility of a plateau after 5-7 days of infusion at 7.5%-8%. The average rate of replacement from days 1 to 5 was 1.3% per day and was determined by linear regression analysis. Acute toxic effects, especially mucositis, were severe enough to require delays in the radiation therapy. Eleven of 12 patients treated had complete clinical remissions. Seven of these patients remain clinically free of local disease at the time of death or most recent follow-up. CONCLUSIONS: The level of IdUrd incorporation and cell labeling should be adequate to produce sensitization. However, the treatment as prescribed in this study (two 14-day infusions of IdUrd during radical radiotherapy with only one planned split) was not completed in a single patient because of either dose-limiting hematologic toxicity or severe mucositis necessitating treatment break. Since this particular regimen is not tolerable, future protocols will have shorter exposures to IdUrd. IMPLICATIONS: Previous regimens using halogenated pyrimidine radiosensitizers have generally used protracted drug delivery schedules. In this study, a high level of IdUrd labeling was measured after 5-7 days of drug infusion. The halogenated pyrimidines deserve further study with the use of repetitive short courses to reduce toxicity and possibly improve efficacy.

Adult↗