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Biomedical subjects

J A Cook

Publications and source records attributed to J A Cook.

At least 109 records · Page 6Linked to original sources

Service delivery using consumer staff in a mobile crisis assessment program.

Interest has developed in the use of mental health consumers as staff members in community programs for persons with serious mental illness. The present study investigates consumer service delivery in a mobile assessment program designed to assist homeless people with severe psychiatric disorders. Consumer and non-consumer staff were generally comparable. Results suggest that consumer staff engaged in more street outreach and were less often dispatched for emergencies. There was a trend for consumer staff to be more likely to certify their clients for psychiatric hospitalization. In sum, consumer staff appear to provide a valuable contribution to this form of service delivery.

Community Participation↗

Evolution of the management of hydrocephalus associated with acoustic neuroma.

The management of hydrocephalus in association with a cerebellopontine angle tumor is controversial. There is a widely held belief that initial therapy should always be directed toward treatment of hydrocephalus before definitive surgery. The potential problems of cerebrospinal fluid (CSF) shunting and drainage have to led to an evolution in the management of hydrocephalus at St. Vincent's Hospital. There is growing evidence that complete removal of cerebellopontine angle tumors will result in resolution of hydrocephalus without requiring other methods of CSF decompression. The authors present their experience of 14 patients with hydrocephalus found in a recent series of 104 consecutive cases of acoustic neuroma. This study has detected a significant correlation between hydrocephalus and increasing tumor size (P = .0234). The mean tumor size in this series was 3.8 cm. The series has also demonstrated that successful. safe, and complete tumor removal can be achieved without CSF drainage before surgery.

Adult↗

Activation of thromboxane A2 receptors alters lipopolysaccharide-induced adherence of THP-1 cells.

U46619, a thromboxane A2 (TXA2) mimetic, inhibits human monocyte chemotactic responses, suggesting that TXA2, an arachidonic acid metabolite, may alter monocyte adhesion. We tested the hypothesis that TXA2 alters Lipopolysaccharide (LPS)-induced adhesion of THP-1 cells, a human monocytic leukemia cell line. Salmonella enteritidis endotoxin (1 microgram/mL) induced a significant (p < .05; n = 6) increase in the adherence of THP-1 cells (basal, 5.7 +/- 1.8 micrograms/well; LPS, 78.8 +/- 4.9 micrograms/well). Treatment of THP-1 cells with indomethacin or TXA2 receptor antagonists before LPS stimulation significantly (p < .05) enhanced adhesion, suggesting that endogenously produced TXA2 or prostaglandins alter LPS-induced THP-1 cell adhesion. TXA2 mimetics significantly decreased (p < .05; n = 5 and n = 3, respectively) LPS-induced THP-1 cell adhesion. This effect was blocked by three structurally dissimilar TXA2 receptor antagonists. These results support the hypothesis that TXA2 alters LPS-induced adhesion of THP-1 cells.

Cell Adhesion↗

The nasal response to isometric exercise in non-eosinophilic intrinsic rhinitis.

The exact pathophysiology of intrinsic rhinitis is not fully understood. The generally held belief is that it is due to an imbalance between the outflow of the nasal sympathetic and parasympathetic nervous systems, perhaps due to excessive parasympathetic or reduced sympathetic activity. In this study the nasal airway response to a predominantly sympathetic stimulus, isometric exercise, was studied in 19 patients with intrinsic rhinitis and compared with 16 normal patients. Isometric exercise took the form of a handgrip stimulus using a hand dynomometer. Following sustained handgrip, a small fall of nasal resistance in the normal group (0.058 kPas/1) and a moderate rise in nasal resistance in the rhinitis group (0.242 kPas/1) was found. Pulse and blood pressure changes were the same in both groups with a significant rise in pulse rate and diastolic blood pressure. The study shows that there is an abnormal response to isometric exercise in intrinsic rhinitis, perhaps due to relative nasal sympathetic hyposensitivity.

Airway Resistance↗

The diving reflex in non-eosinophilic non-allergic rhinitis.

The usual nasal response to head submersion in aquatic mammals is an increase in resistance to airflow, the so-called diving reflex. Although less well developed in humans, it is nevertheless present. It is likely to occur due to a relative increase of parasympathetic over sympathetic control of the nasal vasculature. Non-eosinophilic non-allergic rhinitis is thought to be due to a similar imbalance and we have attempted to establish whether the diving reflex is abnormal in this condition. Sixteen normal subjects and 18 subjects with non-eosinophilic non-allergic rhinitis (NENAR) underwent simulated diving using the "cold face test'. Expiratory total nasal airway resistance (ETR) was measured before and after the test by means of active anterior rhinomanometry. There was no significant increase in ETR in the normal group but a significant increase in ETR in the NENAR group (pre-test median ETR-0.464 kPa.s.l(-1). post-test median ETR 0.667 kPa.s.l(-1), (Wilcoxon's signed rank test P < 0.05). The change in median ETR in the NENAR group was also significantly higher than the median change in ETR in the normal group (Mann-Whitney, extract probability P = 0.04). We conclude the nasal airway response to simulated diving in NENAR is abnormal.

Airway Resistance↗

A prospective controlled study of high-resolution thyroid ultrasound in patients with globus pharyngeus.

The sensation of a lump in the throat may be the presenting symptom of thyroid enlargement, but the majority of thyroid abnormalities are undetectable by clinical examination. The thyroids of 43 patients with globus pharyngeus and 33 controls were prospectively examined by high-resolution ultrasound, to test the hypothesis that a higher incidence of impalpable thyroid abnormalities exists in patients with globus pharyngeus than in the normal population. Abnormalities were present in 31/43 (72%) patients with globus and in 11/33 (33%) controls (P < 0.001). Of the patients with globus, 17 had solitary nodules or cysts, 10 had multiple abnormalities and diffuse abnormality was present in four patients. Solitary nodules ranged from 4 to 29 mm. Impalpable, ultrasound-detectable abnormalities are significantly more common in patients with globus pharyngeus than in controls. Abnormalities of the thyroid gland may be responsible for globus symptoms.

Adult↗

A cross sectional study of renal involvement in tuberous sclerosis.

Renal disease is a frequent manifestation of tuberous sclerosis (TSC) and yet little is known about its true prevalence or natural history. We reviewed the notes of 139 people with TSC, who had presented without renal symptoms, but who had been investigated by renal ultrasound. Information on the frequency, type, and symptomatology of renal involvement was retrieved. The prevalence of renal involvement was 61%. Angiomyolipomas were detected in 49%, renal cysts in 32%, and renal carcinoma in 2.2%. The prevalence of angiomyolipoma was positively correlated with age, compatible with a two hit aetiology. Renal cysts were the commoner lesion in young children, and their prevalence did not appear to be age related. Renal investigation in people with TSC had been inconsistent and limited. We suggest guidelines for renal investigation in those with TSC.

Adolescent↗

Hearing results following modified radical versus canal-up mastoidectomy.

Modified radical mastoidectomy (MRM) provides relatively safe surgical access for the removal of chronic middle ear and mastoid disease and gives reproducible results. However, it had been suggested that hearing may not be as good as that after "intact canal wall mastoidectomy" (ICWM). This paper reviews 153 tertiary referrals suffering from extensive disease who underwent MRM and compares their hearing results with those obtained by other authors using ICWM and MRM and a variety of reconstructive techniques. In this study there were no dead ears and no significant changes in bone conduction despite prolonged drilling and extensive disease. Hearing results after MRM were found to be better after primary surgery than after revision and better in the presence of an intact stapes. No rigid prostheses were used at first-stage surgery. There were no significant differences found between hearing results obtained by MRM in this series and other published results of canal wall down mastoidectomy and ICWM, irrespective of the use of ossicular replacement prostheses.

Adolescent↗

Radiation sensitisation by nitric oxide releasing agents.

Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (microM) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholinosydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells.

Animals↗

The effect of intranasal fluticasone propionate on the diving reflex in patients with non-eosinophilic non-allergic rhinitis.

The usual nasal response to head submersion in aquatic mammals is an increase in resistance to airflow, the so-called "diving reflex". Although less well-developed in humans, it is nevertheless present. It is likely to occur due to a relative increase of parasympathetic over sympathetic control of the nasal vasculature. Non-eosinophilic non-allergic rhinitis is thought to be due to a similar imbalance and we have attempted to establish whether the diving reflex is abnormal in this condition and whether intranasal fluticasone propionate for 6 weeks has any effect in modifying the nasal response.

Administration, Intranasal↗

Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli.

Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2). Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO.

Catalase↗

Nitric oxide protects against alkyl peroxide-mediated cytotoxicity: further insights into the role nitric oxide plays in oxidative stress.

Endogenously formed nitric oxide (NO) possesses diverse properties such as regulating physiological functions, exerting specific toxic effects, and protecting against various toxic substances. Recent studies suggest that in the presence of reactive oxygen species, NO can serve as an antioxidant. We show here that NO delivered from the NO donor compound, PAPA/NO (NH2(C3H6)(N[N(O)NO](C3H7)), protects Chinese hamster V79 lung fibroblasts from the cytotoxicity of t-butyl hydroperoxide and cumene hydroperoxide. In contrast, the other end products of PAPA/NO degradation in aqueous solution, NH2(C3H6)NH(C3H7) and nitrite, did not protect. The NONOate DEA/NO releases NO six times faster than PAPA/NO, yet did not afford protection, which implies that NO must be present throughout the alkyl hydroperoxide exposure. Measurements of NO concentrations released from PAPA/NO suggest that micromolar levels protect against cytotoxicity induced by alkyl hydroperoxides. These findings demonstrate that the flux of NO sustained over the duration of the peroxide exposure determines protection and not the total of NO delivered. These results suggest that concentrations of NO produced in the microenvironment of endothelial cells are high enough to protect cells from Fenton-type-mediated toxicity and support the premise that NO may exert a salutary effect in certain diseases associated with membrane damage.

Alkylating Agents↗

A "cysteineless" GLUT1 glucose transporter has normal function when expressed in Xenopus oocytes.

To test the role of cysteines in the function of GLUT1 glucose transporter, site-directed mutagenesis was used to replace all six GLUT1 cysteines with serine residues. When the individual and combined Cys-->Ser mutants were expressed in Xenopus laevis oocytes, zero-trans uptake of 3-O-methylglucose was comparable to that seen in native GLUT1. The "cysteineless" construct also retained the kinetic features of GLUT1, including an asymmetric transport mechanism and similar substrate and inhibitor affinities. Whereas GLUT1 transport was inhibited by sulfhydryl reagents, that of the "cysteineless" construct was not. These results show that cysteines are not required for GLUT1 function or oligomer formation. The "cysteineless" construct may therefore serve as a template for reintroducing cysteines back into GLUT1 at sites useful for testing transporter structure and function.

3-O-Methylglucose↗

An in vitro flow model to study streaming during pelvic intra-arterial drug infusions.

Regional delivery of suitable drugs by intra-arterial infusion may offer a therapeutic advantage. High concentrations in the tumor are sought with reduced systemic toxicity. Adequate mixing of drug solutions with perfusing blood is essential to provide uniform distribution of drug to tumor-bearing tissue distal to the infusion site. Using a glass model of the iliofemoral and pelvic arteries, we have demonstrated that a streaming phenomenon occurs. Laminar "streamers" of slowly infused drug solution originate at the catheter tip and proceed nonuniformly into distal arterial branches. The intensity of streaming and the pattern of distribution are highly sensitive to catheter tip placement and quite unpredictable. The consequence of regional therapy under streaming conditions is severe maldistribution of drug in the infused tissues with potentially high levels delivered to normal tissues and simultaneous subtherapeutic levels delivered to tumor. Our in vitro model can be used to test appropriate infusion techniques that enhance mixing such as pulsed infusions and novel catheter designs.

Femoral Artery↗

Identification of highly conserved loci by genome painting.

Fluorescence in situ hybridization was used to identify patterns of DNA similarity among the genomes of several rodent taxa. Total genomic or Cot-1 DNAs were used as hybridization probes against metaphase preparations across different taxonomic levels, including three species of Microtus (suborder Sciurognathi), three species of Microtus (suborder Sciurognathi), Mus musculus (suborder Sciurognathi) and Ctenomys steinbachi (suborder Hystricognathi). The hybridization patterns of Mus or Peromyscus (sciurognath) DNA to Mus metaphases, which were consistent with what is known of the satellite sequences in these species, demonstrated the efficacy of this approach for molecular cytogenetics and evolutionary biology. Additional hybridizations to chromosomes of Ctenomys or Microtus identified loci consisting of highly conserved DNA sequences. This approach has proved useful in investigating genome homologies across divergent rodent lineages. Chromosome microdissection can be used to characterize these regions further.

Animals↗