Mental health services--primary concerns for the future.
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Biomedical subjects
Publications and source records attributed to M King.
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BACKGROUND: What should happen when an outpatient fails to attend a psychiatric clinic? Guidelines from the General Medical Services Committee suggest that general practitioners (GPs) have no further responsibility of care for a patient once a referral to a psychiatrist has been made. This raises questions about the formulation of effective management plans for those patients with whom psychiatric services find it difficult to engage due to non-compliance with assessment and follow-up. AIMS: To investigate communication between GPs, patients, and psychiatrists at referral and following attendance or non-attendance at outpatient appointments. METHOD: A prospective study of a random sample of attenders and non-attenders at psychiatric outpatient clinics. Patients and GPs were interviewed to obtain data about the referral process. GPs' views on communication from psychiatrists and the appropriate course of action following clinic non-attendance were investigated. The quality of referral and clinic letters for attenders and non-attenders was compared. RESULTS: There was no difference in the quality of referral letter for attenders and non-attenders. Psychiatrists were less likely to write to GPs about follow-up patients' appointments than new patients' appointments; communication was least likely when a follow-up patient missed their appointment. GPs considered follow-up non-attenders were more likely to need a further appointment than new patient non-attenders, but did not identify a role for themselves in engaging with follow-up non-attenders. CONCLUSION: Communication between GPs and psychiatrists about new patients seems adequate. However, there are important deficits in communication from psychiatrists to GPs about follow-up patients, especially non-attenders who are often more severely ill and difficult to engage. An effective response for this group is likely to need cooperative health and social service action rather than rigid guidelines concerning clinical responsibility.
The evaluation of the outcome of health services technologies is a requirement for their efficient provision in clinical practice. The most reliable evidence for treatment efficacy comes from randomized trials. Randomized trials in general practice pose particular methodological and practical difficulties. In this paper, we discuss how best to plan and manage a clinical trial in this setting. We base our discussion on our experience of conducting randomized trials to evaluate the effectiveness of brief psychotherapy in general practice.
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Reissner's membrane forms a partition between the endolymphatic and perilymphatic cochlear compartments. Expression of the P2X2 receptor subunit which assembles to form ATP-gated ion channels was detected in guinea-pig Reissner's membrane using the reverse transcription polymerase chain reaction (RT-PCR). The P2X2 receptor subunit protein was localized to the epithelial cells which line the endolymphatic surface of Reissner's membrane using confocal immunofluorescence. The P2X receptor expression in Reissner's membrane was functionally confirmed using whole-cell voltage-clamp. An inwardly rectifying conductance was activated in Reissner's membrane epithelial cells in the presence of extracellular ATP (100 microM). This conductance had a pharmacological profile compatible with the P2X2 receptor designation, but exhibited substantial desensitisation which may be attributable to additional P2X receptor subunits. This study indicates that extracellular ATP, a humoral factor within scala media, acts via ATP-gated ion channels expressed by Reissner's membrane epithelial cells to decrease the driving force for sound transduction.
Orphanin FQ/nociceptin (OFQ/N) is a recently identified neuropeptide with high affinity for the orphan opioid receptor. OFQ/N blocked morphine analgesia in mice in a dose-dependent manner, as well as the analgesic actions of [D-Pen2, D-Pen5]enkephalin (DPDPE), morphine-6 beta-glucuronide, trans-3,4-dichloro-N-[2-(1-pyrrolindinyl)-cyclohexyl]-benzeneac eta mide, methane sulfonate hydrate (U50,488H) and naloxone benzoylhydrazone. These actions are anti-analgesic, because OFQ/N also blocked clonidine analgesia and OFQ/N was inactive against the inhibition of gastrointestinal transit by morphine. Although OFQ/N was quite potent in these paradigms, two truncated forms, OFQ/N(1-11) and OFQ/N(1-7), were inactive. An antisense oligodeoxynucleotide targeting the first coding exon of KOR-3, the mouse homolog of the orphan opioid receptor, effectively prevented the anti-opioid actions of OFQ/N, confirming the importance of the orphan opioid receptor in this action.
Patch-clamp techniques were used to characterize the channel activity of mitochondrial inner membranes of two human osteosarcoma cell lines: a mitochondrial genome-deficient (rho0) line and its corresponding parental (rho+) line. Previously, two high conductance channels, mitochondrial Centum picoSiemen (mCS) and multiple conductance channels (MCC), were detected in murine mitochondria. While MCC was assigned to the protein import in yeast mitochondria, the role of mCS is unknown. This study demonstrates that mCs and MCC activities from mouse mitochondria are indistinguishable from those of human mitochondria. The channel activities and their functional expression levels are not altered in cells lacking mtDNA. Hence, rho0 cells may provide a model system for elucidating the role of mitochondrial channels in disease processes and apoptosis.
Mucolytic treatment with rhDNase is part of the current therapy for cystic fibrosis (CF) lung disease. The Flutter valve, a device for enhancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter valve leads to oscillations of expiratory airflow, improving mucus viscoelasticity and stimulating clearance. The goal of our in vitro study was to evaluate the individual and combined effects of Flutter valve oscillations and rhDNase treatment on the viscoelastic (rheological) properties of CF sputum. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: 1) baseline sample with no treatment applied; 2) application of oscillations generated by airflow through the Flutter valve; 3) incubation at 37 degrees C for 30 min with 10% vol/wt rhDNase (Pulmozyme) to achieve a final concentration of 2.5 microg/mL (approximately 100 nM); 4) combination of Flutter valve oscillations and 10% vol/wt normal saline (0.9% NaCl); 5) combination of Flutter valve oscillations and 10% vol/wt rhDNase at 2.5 microg/mL final concentration. For each protocol, the mucus rigidity index (log G* at 1 rad/s) was measured at baseline and at 30 min. Values are presented as mean+/-SEM. The cough clearability index (CCI) was computed from measurements of mucus viscoelasticity, based on relationships established in model studies. Flutter valve treatment alone did not result in a significant reduction in the rigidity of CF sputum (2.24+/-0.13 vs. 2.11+/-0.13, P=0.19), nor did rhDNase (2.5 microg/mL) alone, although we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensitive to molecular weight reduction. In comparison to individual treatments, combined treatment with Flutter valve oscillations and rhDNase significantly reduced the mucus rigidity to 1.85+/-0.19 from 2.24+/-0.13 (P< 0.001), consequently increasing the predicted clearability of the sputum (from 1.09+/-0.26 to 1.83+/-0.48, P=0.012). These in vitro results suggest that a combination of biochemical treatment (e.g., DNase) and mechanical oscillation may have a better therapeutic potential for mucus clearance in CF lung disease.
We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.
Ten probands with moderate to severe developmental delay were found to have a supernumerary inv dup (15) chromosome. These patients and their families were studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms associated with the 15p short arm suggested a maternal derivation for the marker chromosome in all informative cases. One marker was directly maternally inherited. Molecular analysis employing Southern blotting and polymerase chain reaction (PCR) of microsatellite repeats demonstrated the presence of extra alleles in the 15q11q13 region. All ten of the probands demonstrated an extra band at one or more locus without recourse to densitometry. All of the inv dup (15) markers were comparable in size to a G group chromosome but there were differences in the positions of the breakpoints in 15q. There was an inconsistent relationship between marker size, gene dosage and severity of phenotype.
BACKGROUND: The current spectrum of penetrating trauma presenting to Auckland Hospital is described and whether this differs from the situation in 1983 is determined. METHODS: Prospectively collected trauma registry data were used to describe the characteristics of penetrating trauma cases presenting to Auckland Hospital during the 1995 calendar year. Using data collected from a previous study in 1983, comparisons were made of the incidence, severity, and outcome of penetrating trauma cases between these two cohorts. RESULTS: In 1995, 96 patients, representing 7.3% of total trauma admissions, presented to Auckland Hospital following penetrating trauma. Of these, 32 patients were admitted by the trauma team via the resuscitation room, 13 were admitted to the intensive care unit (ICU) and four died. The median age of these patients was 30 years and median Injury Severity Score, 4. In comparison with the 1983 patients there was no demonstrable change in the numbers of patients or their length of stay. Although injury severity was similar in the 1995 cohort, fewer patients were admitted to the ICU. Mortality of the 'trauma team' group was 4/32 in 1995 compared with 7/33 in 1983. CONCLUSIONS: Despite public concerns, the frequency of penetrating trauma cases presenting to Auckland Hospital was similar in 1995 and 1983. There is a non-significant decrease in length of stay and mortality in the 1995 cohort.
The combination of both Cl- and HCO3- secretion inhibitors causes an accumulation of mucins within the submucosal gland ducts of acetylcholine (ACh)-treated bronchi [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997], suggesting indirectly that these agents block airway gland liquid secretion. The present study tested the hypotheses that ACh-stimulated liquid secretion is driven by Cl- and HCO3- secretion and that inhibition of this process leads to secretion of a dehydrated mucus with altered rheological properties. Excised distal bronchi from pigs were pretreated with either a combination of Cl- and HCO3- secretion inhibitors (bumetanide, acetazolamide, dimethylamiloride, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) or the dimethyl sulfoxide vehicle and were then treated with ACh to induce secretion. The rate of mucus liquid secretion was substantially reduced when the airways were pretreated with the anion secretion inhibitors. Mucus liquid from inhibitor-pretreated airways contained almost threefold more nonvolatile solids than the control liquid. Rheological analysis revealed that mucus liquid from inhibitor-pretreated airways expressed a significantly greater log G* (rigidity factor), whereas tangent delta (recoil factor) was significantly reduced. These results suggest that 1) ACh-induced liquid secretion in bronchi is driven by both Cl- and HCO3- secretion and 2) inhibition of ACh-induced liquid secretion results in the secretion of mucus with a reduced water content and altered rheological properties.
Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa to epithelial cells (1). The initial purpose of this study was to evaluate the potential of dextran to alter the rheology and ciliary transportability of CF sputum prior to initiation of a clinical trial in patients with CF. Sputum samples were collected from 25 patients with CF not receiving rhDNase therapy for use in in vitro testing. Aliquots of CF sputum were treated with 10% vol. Ringer's or the same volume of Dextran 4000 to give a final concentration of 0.4% (4 mg/ml) or 4% (40 mg/ml) dextran in the sputum. Dog mucus samples were collected from seven healthy, anesthetized dogs from the endotracheal tube cuff. Aliquots of dog mucus were subjected to the same concentrations of dextran as the CF sputum. All treated samples were incubated for 30 min at 37 degrees C, and their rheologic properties (viscoelasticity) were evaluated by magnetic microrheometry. For 17 of the sputum samples, frog palate mucociliary transportability was determined from sputum movement on the ciliated, mucus-depleted frog palate, relative to native frog mucus control. Spinnability (cohesiveness) was evaluated by the filancemeter technique for eight sputum samples. Overall, whether for CF sputum or healthy dog mucus, Dextran 4000 treatment significantly reduced viscoelasticity and increased predicted mucociliary and cough clearability. Direct measurements of sputum mucociliary clearability on frog palate increased significantly with 0.4% dextran and 4% dextran compared with saline control. Sputum spinnability (cohesiveness) decreased significantly with both dextran concentrations, too. The effects on viscoelasticity and spinnability were greater at 4% than at 0.4%. There was a significant positive correlation between spinnability and viscoelasticity, and negative relationships between spinnability and both forms of clearability as predicted from viscoelastic measurements. This study suggests that treatment with Dextran 4000 can reduce the crosslink density and cohesiveness of CF and improve mucociliary and cough clearability. Dextran 4000 is an inexpensive and nontoxic agent that may be of benefit in patients with CF lung disease and perhaps in other respiratory disease where mucus retention is an important feature.
Respiratory tract mucus is a viscoelastic gel, the rheological properties of which are determined mainly by its content of mucous glycoproteins and water. The rheology and quantity of mucus, in concert with ciliary factors, are the major determinants of mucociliary clearance. A wide range of animal models for studying the secretion and clearance of mucus are available. Ex vivo models, such as the frog palate or excised bovine trachea, provide direct, meaningful data regarding the clearability of mucus. Rodent models of chronic bronchitis, based on irritant gas or cigarette smoke exposure, show important features of the human condition in a relatively short time. The rheological characterization of mucus is made difficult by the small quantities obtainable, particularly from normal animals. Large animal models, such as the dog or sheep, although more expensive, offer many advantages, such as the ability to carry out long-term serial measurements, and to make integrated measurements of the clearance of mucus, ciliary function, epithelial ion transport, and the rheology of mucus in the same preparation.
Examined the psychological correlates related to experiencing the death of a parent, the main and interactive effects of sex, race, and age on youth distress and the degree of cross-informant correspondence on the outcome measures. The predominately minority sample included 80 bereaved youth and 45 nonbereaved youth. Youth and their legal guardians completed a battery of questionnaires, including measures assessing the youth's psychological symptomatology. Results revealed that bereaved youth manifested greater psychological and behavior problems than their nonbereaved counterparts on guardian-reported measures (Child Behavior Checklist [CBCL]). The clinical significance of parental death experienced during childhood is indicated by the magnitude of distress exhibited by the bereaved sample; almost one quarter of bereaved youth scored in the clinical distress range (T score > or = 63) on the CBCL Externalizing and Internalizing Distress scales. The effect of parental death on guardian-reported externalizing distress was moderated by race, such that distress levels did not significantly differ between bereaved and nonbereaved minority youth but did differ significantly among bereaved and nonbereaved nonminority youth. Finally, the degree of cross-informant agreement was relatively low but consistent with prior studies. Study implications for interventions with bereaved youth and directions for future research are discussed.
OBJECTIVE: The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device. MATERIALS AND METHODS: To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer. RESULTS: No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.