bluuebunny/crossref_metadata_2025 huggingface dataset:
Mode of delivery is not associated with asthma or atopy in childhood
Authors: Maitra A. , Sherriff A. , Strachan D. ,   ALSPAC Study Team, Henderson J.
Published: September 2004

Background
Caesarean‐section delivery has been associated with the subsequent development of atopy and wheezing in childhood.

Objective
To examine the association between mode of delivery (vaginal vs. caesarean section) and development of atopy, asthma and wheezing disorders in a population‐based cohort of children.

Methods
The Avon Longitudinal Study of Parents and Children is a longitudinal birth cohort of children born 1 April 1991 to 31 December 1992. Mode of delivery was categorized as vaginal (including forceps and ventouse extractions) or caesarean section (elective and emergency). Primary outcomes were parental report of asthma or wheezing between 69 and 81 months of age, physician‐diagnosed asthma (PDA) at 91 months of age and atopy at 7 years by skin prick testing. Possible confounding factors were considered in a multivariable logistic regression model.

Results
Total livebirths were 14 062, from which were selected 12 367 born to mothers resident in a defined area and delivered in one of two major obstetric hospitals. Of these infants, 10 980 (88.8%) were delivered vaginally and 1387 (11.2%) by caesarean section. Outcome data were available for 7495 (61%) subjects (asthma 69–81 months); 7389 (60%) (wheeze 69–81 months); 7196 (58%) (PDA 91 months) and 5916 (48%) (atopy 7 years). Adjusted odds ratios [95%confidence interval] for caesarean section compared with vaginal delivery were not statistically significant for any outcome we considered: asthma 69–81 months 1.16 [0.9, 1.5]; wheeze 69–81 months 0.95 [0.7, 1.3]; PDA 1.14 [0.9, 1.4]; atopy 1.04 [0.8, 1.3].

Conclusion
Delivery by caesarean section was not associated with the subsequent development of asthma, wheezing or atopy in later childhood in this population.
The flow‐cytometric determination of basophil activation induced by aspirin and other non‐steroidal anti‐inflammatory drugs (NSAIDs) is useful for in vitro diagnosis of the NSAID hypersensitivity syndrome
Authors: Gamboa P. , Sanz M. L. , Caballero M. R. , Urrutia I. , Antépara I. , Esparza R. , De Weck A. L.
Published: September 2004

Background
Hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs), manifested by cutaneous symptoms and/or airway manifestations represent 20–25% of all hypersensitivity reactions to drugs. Today, it is still claimed that no in vitro diagnostic tests exist for that condition and that the only way to confirm the diagnosis is a provocation challenge.

Objective
The objective of this study was to assess whether NSAIDs may provoke blood basophil activation in vitro in such patients, as detected by a flowcytometric technique.

Methods
Sixty NSAID hypersensitive patients (38 with cutaneous, 20 with airway and two with cutaneous and airway symptoms) and 30 control patients (15 asthmatics) were selected. Their hypersensitivity was confirmed by documented history indicating at least two clinical episodes to two or more different NSAIDs or by positive oral provocation challenge. Isolated buffy coat leukcocytes were stimulated in vitro with aspirin, paracetamol, metamizol, diclofenac, and naproxen. The percentage of activated basophils was evaluated by an anti‐CD63.

Results
Aspirin showed a sensitivity of 43.3%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.4%. For the other NSAIDs, the sensitivity and specificity values were: for paracetamol 11.7% and 100%, for metamizol 15% and 100%, for diclofenac 43.3% and 93.3% and for naproxen 54.8% and 74.1%. When considering the first four NSAIDs, the global sensitivity raised to 63.3% and specificity to 93.3%. If the number of tests is to be limited for practical reasons, the combination of acetylsalicylic acid and diclofenac at two concentrations yields a sensitivity of 58.3% and a specificity of 93.3%.

Conclusions
Flowcytometric determinations of basophil activation following stimulation with NSAIDs show a high sensitivity (60–70%) with specificity above 90%. So this test may help avoiding some cumbersome and dangerous provocation challenges.
A survey of the quality of information leaflets on hayfever available from general practices and community pharmacies
Authors: White P. , Smith H. , Webley F. , Frew A.
Published: September 2004

Background
Hayfever affects at least one in 10 people. The majority of hayfever is managed in the community setting where the management options are pharmaceutical and behavioural. Hayfever medications are available over the counter and on prescription from the general practitioner. Patient information leaflets are published to augment the advice given and to promote self‐management, but these leaflets have rarely been subjected to critical review.

Objective
To assess the quality of patient information leaflets written for people with hayfever and available from general practices and from community pharmacists.

Method
A structured review of patient information leaflets about hayfever. During the peak grass pollen season copies of all leaflets available were collected from a random sample of community pharmacists and general practices in Wessex. The characteristics of the leaflet were recorded and the contents and presentation of each one was reviewed using the British Medical Association patient information appraisal system. Readability was assessed using the Simple Measure of Gobbledegook (SMOG). Two allergy‐accredited specialists assessed each leaflet for accuracy.

Results
During the peak pollen season no leaflets were available in 30% of the Community Pharmacists and 23% general practices. In total, 38 different leaflets were identified. All the leaflets reviewed were written for adults. Forty‐seven percent of the leaflets had no publication date and one‐third of those dated were at least 5 years old. In general the leaflets scored highly on issues of presentation, but less than half contained information on the full range of management and treatment options, many being biased towards a single or limited range of interventions. Seventy‐nine percent leaflets were produced or sponsored by pharmaceutical companies and gave prominence to their own products. All the leaflets had readability scores requiring at least secondary education (SMOG score equal or greater than 9). At least one factual inaccuracy was identified in four‐fifths of leaflets.

Conclusion
A large number of leaflets are published for people with hayfever, but they are of variable quality and not accessible to all patients because of limited distribution or high readability scores. If all patients are to benefit from written information the authors and publishers of leaflets need to follow published recommendations, especially with respect to content and readability. In the absence of a national public health information strategy or a body that systematically vets patient information materials, clinicians must pay attention to the quality of information provided for or obtained elsewhere by their patients.
Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double‐blind, placebo‐controlled study
Authors: Mirone C. , Albert F. , Tosi A. , Mocchetti F. , Mosca S. , Giorgino M. , Pecora S. , Parmiani S. , Ortolani C.
Published: September 2004

Background
The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America.

Objective
We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia.

Methods
Thirty‐two patients (18 M/14 F, mean age 36.78, range 23–60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double‐blind, placebo‐controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 μg of Amb a 1 was administered at 4‐week intervals after the build‐up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial.

Results
Twenty‐three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2‐fold, P=0.0001) in the active group whereas a slight increase (1.07‐fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78‐fold, P=0.002).

Conclusion
Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.
Mixed antibody and T cell responses to peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 in an oral sensitization model
Authors: Van Wijk F. , Hartgring S. , Koppelman S. J. , Pieters R. , Knippels L. M. J.
Published: September 2004

Background
Peanut allergy is known for its severity and persistence through life. Several peanut proteins have been identified as allergenic and are indicated as Ara h 1–7. Very little is known about the mechanisms that underlie sensitization to peanut proteins.

Objective
The purpose of the present study was to reveal the immune responses that are induced against peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 during sensitization, including the very early responses.

Methods
Humoral and T cell responses against peanut and the peanut allergens were examined in an early and later stage of sensitization in an established murine model of peanut anaphylaxis. Therefore C3H/HeJ mice were orally exposed to two different doses of peanut extract plus cholera toxin.

Results
Oral sensitization to peanut was characterized by an antigen‐induced mixed cytokine response in the spleen (IL‐4, IL‐5, IL‐10 and IFN‐γ), which could already be observed 7 days after the onset of exposure. Additionally, polyisotypic humoral responses (IgE, IgG1 and IgG2a) against peanut were found in the serum. Moreover, we demonstrated that these T helper (Th)1/Th2 cytokine and antibody responses were also directed specifically against the major peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6.

Conclusions
This study implicates that both Th1 and Th2 phenomena are involved in the development of peanut allergy in the C3H/HeJ murine model. Furthermore, we show that the present oral model is suitable to examine immune responses to food allergens during different stages of sensitization upon treatment with a whole food extract.
Regulation of glucocorticoid receptor gamma (GRγ) by glucocorticoid receptor haplotype and glucocorticoid
Authors: Stevens Adam , Donn Rachelle , Ray David
Published: September 2004

objective  To measure glucocorticoid receptor gamma (GRγ) expression in transformed lymphocytes from individuals of known GR gene haplotype. Recently, a glucocorticoid receptor haplotype (GAT) has been described that associates with increased sensitivity to dexamethasone. As there is strong linkage disequilibrium across the gene, this haplotype is likely to extend through exon 3, altered splicing of which generates the GRγ isoform, a splice variant with impaired transactivation activity. Therefore we proposed that the GR haplotype affects glucocorticoid sensitivity either by influencing GRγ expression basally, or in response to Gc exposure.

design  We have measured expression of GRγ, using a validated RT–PCR assay in human B lymphoblast cells of known haplotype under basal conditions, and after dexamethasone treatment.

patients  The A549 human lung cell line and normal volunteers, five with the GAT GR haplotype and three with the CGA haplotype.

measurements  Relative expression of GRγ compared to total GR mRNA.

results  GRγ made up 5–6% of all the GR transcripts. There was no effect of carriage of the GR gene GAT haplotype on this expression. There was no effect of dexamethasone on relative expression of GRγ.

conclusions  We propose that the GRγ isoform is a product of constitutive splicing, that it does not explain the GR haplotype association with altered glucocorticoid sensitivity, and is unlikely to play an important physiological role in affecting glucocorticoid sensitivity. As glucocorticoids do not affect GRγ expression, relative to total GR, this splice variant is unlikely to influence glucocorticoid treatment response.
Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers
Authors: Wolfe Barbara E. , Jimerson David C. , Orlova Christine , Mantzoros Christos S.
Published: September 2004

objective  Recent findings demonstrating important effects of the adipokines on metabolism, energy homeostasis and body weight regulation have prompted research on the possible role of negative energy balance in altering adipocytokine regulation. The goal of this study was to evaluate the effects of a hypocaloric diet in healthy normal‐weight volunteers. An additional goal was to help clarify the contribution of restricted caloric intake to altered plasma adipokine levels in the eating disorders anorexia nervosa and bulimia nervosa.

design  Participants were studied before and after a 4‐week reduced‐calorie diet (1000–12000 kcal/day).

patients  Subjects included 15 healthy, normal‐weight women (age 22 ± 3 years).

measurements  Plasma concentrations of leptin, soluble leptin receptor protein (sOB‐R), adiponectin, resistin, thyroid hormones and β‐hydroxybutyrate were determined following overnight fast before and after the 4‐week reduced‐calorie diet.

results  Subjects lost a mean of 3·4 ± 2·1 kg in response to the reduced‐calorie diet. The weight loss phase was associated with a 60·3% decrease in plasma leptin levels (P < 0·001), a 43·5% increase in sOB‐R levels (P < 0·002) and a 16·2% decrease in plasma adiponectin levels (P < 0·04). There was no significant change in plasma resistin levels.

conclusions  These results demonstrate that a modest decrease in energy intake sustained over several weeks may play an important role in altering levels of plasma leptin and sOB‐R. The findings also provide preliminary evidence that, in contrast to previous results in obese subjects, caloric restriction with accompanying weight loss in healthy, normal‐weight volunteers may lead to decreased circulating adiponectin levels. Additional studies will be needed to clarify the contribution of altered energy intake to abnormalities in cytokine levels in the eating disorders.
Gonadotrophin receptor blocking antibodies measured by the use of cell lines stably expressing human gonadotrophin receptors are not detectable in women with 46,XX premature ovarian failure
Authors: Tonacchera Massimo , Ferrarini Eleonora , Dimida Antonio , Agretti Patrizia , De Marco Giuseppina , De Servi Melissa , Gianetti Elena , Chiovato Luca , Pucci Enrico , Pra Chiara Dal , Betterle Corrado , Aghini‐Lombardi Fabrizio , Vitti Paolo , Pinchera Aldo
Published: September 2004

background  Premature ovarian failure (POF) is defined by cessation of ovarian function after puberty and before the age of 40. The syndrome is characterized by amenorrhoea, oestrogen deficiency and elevated levels of gonadotrophins. Autoimmunity has been proposed as a mechanism for some cases of destruction or malfunction of ovarian follicles. POF is often associated with type I and type II polyglandular autoimmune syndromes. It has also been postulated that receptors such as the LH and FSH receptors might become targets for blocking antibodies and such antibodies could be a cause of ovarian failure.

patients and methods  Sixty‐nine patients with POF isolated or associated with other endocrine autoimmune diseases (autoimmune thyroid diseases, Addison's disease, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis) were studied. All the patients had secondary amenorrhoea. The patient group had a median age of 33·1 years (range 15–57). Ovarian failure had been diagnosed at a median age of 29 years (range 15–39). The median time since diagnosis was almost 1 year but in six patients gonadal insufficiency had appeared 10–30 years earlier. All had a normal chromosomal karyotype (46, XX). Patients with POF were characterized by duration of amenorrhoea > 1 year, with elevated FSH and LH levels and undetectable or low oestrogen levels. Cell lines stably expressing recombinant human LH (CHO‐LHr) and FSH (CHO‐FSHr) receptors were prepared and used to search for antibodies able to inhibit LH‐ or FSH‐stimulated cAMP production. Immunoglobulins extracted from sera of patients with POF were incubated with CHO‐LHr and CHO‐FSHr in the presence of human recombinant CG and FSH, respectively.

results and conclusions  None of the immunoglobulin G (IgG) preparations from patients with POF was able to inhibit the activity of the FSH‐ and CG‐stimulated cAMP production.
Recombinant GH replacement in hypopituitary adults improves endothelial cell function and reduces calculated absolute and relative coronary risk
Authors: Abdu T. A. M. , Elhadd T. A. , Buch H. , Barton D. , Neary R. , Clayton R. N.
Published: September 2004

objective  Adult GH deficiency (GHD) is linked to endothelial dysfunction and vascular disease. We examined the effect of 12 months of GH therapy on endothelial function, C‐reactive protein (CRP) and coronary risk.

design  Open‐design intervention study.

patients  Fourteen GH‐deficient patients (nonsmokers, without diabetes, hypertension or vascular disease) studied before, 6 months and 12 months after GH therapy.

measurements  Flow‐mediated dilatation (FMD), carotid intima–media thickness (IMT) thrombomodulin (TM), E‐selectin, CRP, lipid profile, blood pressure and anthropometric data were recorded. We used the Framingham equation to calculate coronary risk.

results  FMD improved (7·5 ± 1·62 vs. 11·93 ± 1·52, P = 0·038). Overall there was no change in IMT, TM, E‐selectin or CRP. The correlation between TM and FMD showed a trend for statistical significance (r = −0·54, P = 0.056). Changes in CRP correlated with change in IGF‐1 (r = −0·67, P = 0·012); E‐selectin correlated with high density lipoprotein (HDL)‐cholesterol (r = −0·60, P = 0·028), triglycerides (r = 0·68, P = 0·01) and waist‐to‐hip ratio (WHR) (r = 0·71, P = 0·006). Systolic (127·36 ± 4·47 vs. 120·36 ± 3·50, P = 0·017) and diastolic (84·71 ± 2·73 vs. 76·93 ± 2·03, P = 0·005) blood pressure decreased. HDL‐cholesterol increased (0·70 ± 0·05 vs. 0·93 ± 0·06, P = 0·001). WHR decreased (0·90 ± 0·02 to 0·88 ± 0·02, P = 0·043) without changes in weight or body mass index (BMI). Ten‐year absolute (P = 0.009) and relative (P = 0.002) cardiac risk decreased.

conclusion  Biophysical test of endothelial function (FMD) improved after 12 months of GH therapy but there was no significant change in biochemical endothelial or inflammatory markers. Calculated coronary risk decreased mainly due to reduction in systolic and diastolic blood pressure and increase in HDL‐cholesterol.
Characteristics of recovery of adrenocortical function after treatment for Cushing's syndrome due to pituitary or adrenal adenomas
Authors: Klose Marianne , Jørgensen Karsten , Kristensen Lars Østergaard
Published: September 2004

objective  Surgical cure of Cushing's syndrome (CS) is followed by adrenocortical insufficiency, which may be long‐lasting. The aim was to elucidate recovery of adrenocortical function, defined as a normal cortisol response to ACTH stimulation, and the relation to ACTH in patients cured for CS due to pituitary Cushing's disease (CD) or adrenal (AA) adenomas.

design  A retrospective study including 32 patients considered surgically cured for CS (18 CD, 14 AA).

results  Twelve (67%) patients with CD recovered within median 24 months (range 7 months−41/2 years) whereas six did not recover within 3–12 years. Plasma ACTH (p‐ACTH) at time of recovery was not different from p‐ACTH in patients not recovering (P = 0·9). Eleven (79%) patients with AA recovered within 24 months (10 months−4 years) whereas three did not recover within 4–10 years. p‐ACTH at time of recovery was higher compared to patients not recovering (P < 0·04). No differences were observed comparing CD and AA patients concerning preoperative 24‐h urinary free cortisol (UFC) excretion, postoperative unstimulated s‐cortisol or recovery time. By contrast, p‐ACTH measured at time of recovery was higher in AA compared to CD (median 12·3 vs. 4·6 pmol/l) (P < 0·001), whereas plasma dehydroepiandrosterone sulfate (p‐DHEAS) was lower in AA compared to CD (median 300 vs. 1500 nmol/l) (P = 0·02).

conclusion  Recovery of secondary adrenal insufficiency is a slow process in both CD and AA. ACTH measured at time of recovery was significantly higher and DHEAS significantly lower in patients with AA compared to CD, which may suggest different mechanisms of the recovery process and different set points in the glucocorticoid feedback inhibition of ACTH secretion.
Changes in endothelium‐dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism
Authors: Guang‐da Xiang , Hong‐yan Cao , Xian‐mei Zeng
Published: September 2004

objective  This case–control study was carried out to assess the alteration of endothelium‐dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism.

patients and methods  The study subjects included 12 patients with hyperthyroidism and 39 apparently healthy individuals. We performed a subtotal thyroidectomy on the hyperthyroid patients. The endothelium‐dependent arterial dilation was determined with a high‐resolution ultrasound method in each patient at the hyperthyroid stage before treatment (stage H), the euthyroid stage induced immediately before surgery (stage E), and the transient hypothyroid stage 1 or 2 months after surgery (stage L).

results  The flow‐mediated arterial dilation decreased significantly from H to E and from E to L (P < 0·001). As compared with H, baseline blood flow decreased markedly at stages E and L (P < 0·001). The flow‐mediated arterial dilation and baseline blood flow in the control subjects were very close to those at stage E of the hyperthyroid patients. The absolute change in the flow‐mediated arterial dilation showed significant negative correlation with the changes in TSH (r =−0·86, P < 0·001), lipoprotein (a) [Lp(a)] (r =−0·77, P < 0·001) and low density lipoprotein (LDL) (r =−0·79, P < 0·001), and significant positive correlation with changes in fT3 (r =+0·88, P < 0·001). The absolute change in the baseline blood flow showed significant positive correlation with the change in fT3 (r =+0·85, P < 0·001) and significant negative correlation with the change in TSH (r =−0·63, P < 0·01).

conclusion  The endothelium‐dependent arterial dilation increases significantly in untreated hyperthyroid patients, and decreases markedly after a subtotal thyroidectomy. Therefore, we conclude that the endothelium is more responsive to reactive hyperaemia in the hyperthyroid than the euthyroid state.
Rhythmogenesis in Vasopressin Cells
Authors: Brown C. H.
Published: September 2004

Many neurones in the central nervous system possess intrinsic pattern‐generating properties, including vasopressin magnocellular neurosecretory cells. Synaptic input to vasopressin cells is not rhythmically patterned and yet these neurones fire action potentials in a ‘phasic’ activity pattern comprised of alternating periods of activity and silence that each last tens of seconds. This review describes the intrinsic and extrinsic mechanisms that generate phasic activity in vasopressin cells, highlighting recent work that has shown phasic activity to result from feedback modulation of synaptic inputs, and of intrinsic membrane properties, by peptides released from the dendrites of vasopressin cells.
Emerging Functions Of Gonadotropin‐Releasing Hormone II in Mammalian Physiology and Behaviour
Authors: Kauffman A. S.
Published: September 2004

Gonadotropin‐releasing hormone (GnRH) is the central neuroendocrine regulator of the hypothalamic‐pituitary‐gonadal axis. Multiple structural variants of GnRH are present in vertebrates. The first isoform isolated in the mammalian brain (GnRH I) was shown to regulate the release of pituitary gonadotropins. Recently, a second form has been discovered in mammals (GnRH II), both in the brain and periphery. Although it is unlikely to be a primary regulator of gonadotropin release, the highly conserved GnRH II variant appears to have a wide array of physiological functions. In the periphery, GnRH I and II have similar roles in regulating cell proliferation and mediating hormonal secretion from the ovary and placenta in an autocrine/paracrine manner. In the brain, GnRH I and II apparently modulate mammalian reproductive behaviours in different but complementary ways: GnRH I stimulates luteinizing hormone/follicle‐stimulating hormone secretion (and thus gonadal steroids) and promotes sexual behaviour in ad libitum fed animals. By contrast, GnRH II acts as a permissive regulator of female reproductive behaviour based on energy status, as well as a modifier of short‐term food intake. GnRH II has also been implicated in the regulation of calcium and potassium channels in nervous systems of amphibians, functions which may also be present in mammals. Increasing evidence suggests that the effects of GnRH II in both the periphery and brain may be mediated by GnRH receptor subtypes distinct from the type‐1 GnRH receptor. It is likely that this evolutionarily conserved peptide has been co‐opted over evolutionary time to possess multiple regulatory functions in a broad range of biological aspects, including, but not limited to, reproduction. Here, the proposed actions of both neural and peripheral GnRH II in affecting physiology and behaviour are summarized, and an outline of critical directions for future research is proposed.
Ageing and the Diurnal Expression of mRNAs for Vasoactive Intestinal Peptide and for the VPAC2 and PAC1 Receptors in the Suprachiasmatic Nucleus of Male Rats
Authors: Kalló I. , Kalamatianos T. , Piggins H. D. , Coen C. W.
Published: September 2004

Ageing alters fundamental aspects of circadian rhythmicity in mammals; the effects include reduced rhythm amplitude and alterations in period length and in entrainment to the light/dark cycle. Such changes may reflect disruptions in cellular function within the suprachiasmatic nucleus (SCN), the site of the predominant circadian pacemaker. In the SCN, vasoactive intestinal peptide (VIP)‐synthesizing neurones receive various inputs, including retinohypothalamic projections containing pituitary adenylate cyclase activating peptide (PACAP). SCN VIP cells establish connections with local neurones and send efferents beyond the nucleus. Considerable evidence implicates VIP and PACAP in circadian rhythm maintenance and/or entrainment to photic Zeitgebers. These actions involve members of a distinct family of receptors; mRNAs for two such receptors, VPAC2 and PAC1, are present in the SCN. This study used isotopic in situ hybridization to examine the effects of ageing on expression of mRNAs for VIP, VPAC2 and PAC1 in the SCN of male rats under a 12 : 12 h light/dark cycle. Analysis of film autoradiographs from young adult (2–3 months) or aged (19–20 months) rats, at eight time points across the light/dark cycle, showed loss of diurnal rhythmicity and reduced levels for VIP mRNA in the aged group. A diurnal rhythm of VPAC2 receptor mRNA was present in both groups, but its levels were reduced in the aged rats. There were no differences between the two groups for PAC1 receptor mRNA expression. The present results indicate that ageing reduces VIP and VPAC2 receptor mRNA and eliminates diurnal expression of VIP mRNA within the SCN of aged male rats.
17β‐Oestradiol Modulates Glucocorticoid, Neural and Behavioural Adaptations to Repeated Restraint Stress in Female Rats
Authors: Lunga P. , Herbert J.
Published: September 2004

Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17β‐oestradiol on hypothalamic‐pituitary‐adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17β‐oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17β‐oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17β‐oestradiol‐treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin‐releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17β‐oestradiol treatment at the higher dose (120 µg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17β‐oestradiol‐treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17β‐oestradiol‐replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non‐stressed control rats with or without 17β‐oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17β‐oestradiol‐treated rats. After repeated restraint stress, 17β‐oestradiol‐replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17β‐oestradiol‐treated ovariectomized rats, but stress‐induced anxiety behaviour is reduced.
Lewy bodies in the sinoatrial nodal ganglion: Clinicopathological studies
Authors: Okada Yume , Ito Yuji , Aida Junko , Yasuhara Masahiro , Ohkawa Shin‐ichiro , Hirokawa Katsuiku
Published: September 2004

Lewy bodies (LB) are characteristic pathological findings for idiopathic Parkinson disease, and extracranial organs have also been known to exhibit these structures. Clinically, the possible involvement of LB in cardiac dysfunction has attracted attention based on the findings of studies using [123I] metaiodobenzyl guanidine (MIBG) scintigraphy. The purpose of the present study was to investigate the possible involvement of LB in heart disease. A total of 40 autopsy cases consisting of Lewy body disease and Parkinson syndrome were examined. The former were cases with intracranial LB regardless of clinical symptoms, and the latter were cases with parkinsonism but without intracranial LB. The presence of heart disease or an atrial arrhythmia and the results of an MIBG scintigraphy study were clinically examined. The sinoatrial node was examined microscopically and immunohistochemically. The results showed that heart disease and atrial arrhythmia complications were more frequent in cases with Lewy body disease than in cases with Parkinson syndrome and that LB were frequently found in extracranial organs, especially in the sinoatrial nodal ganglion, in cases with Lewy body disease. In the current report, we hypothesized that neuronal changes involving LB in the sinoatrial nodal ganglion may cause arrhythmia and ischemic heart disease as a result of vasoconstriction.
GM‐CSF activates RhoA, integrin and MMP expression in human monocytic cells
Authors: Kohno Yukari , Tanimoto Akihide , Cirathaworn Cintana , Shimajiri Shohei , Tawara Akihiko , Sasaguri Yasuyuki
Published: September 2004

Monocyte migration is one of the key events occurring in the early stage of atherosclerosis. This process includes monocytic adhesion to and penetration through the arterial intima. In such an environment, many factors stimulate the monocytes to enhance integrin activation and extracellular matrix degradation. To investigate the coordinative operation of these two events in relation to monocyte migration, we paid particular attention to the effects of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) on monocytes in terms of RhoA activation and matrix metalloproteinase (MMP) expression. RhoA and integrin clustering were activated by GM‐CSF, monocyte chemoattractant protein‐1 (MCP‐1) and platelet‐derived growth factor‐BB (PDGF‐BB) in human monocytic cell lines. Furthermore, enhancement of migration was observed with stimulation by MCP‐1 and PDGF‐BB. Granulocyte‐macrophage colony‐stimulating factor did not enhance the migration, even though it activated RhoA and integrin. However, GM‐CSF is known to stimulate monocytes to express MCP‐1, suggesting the presence of an indirect mechanism for GM‐CSF‐mediated migratory activity. In contrast, only GM‐CSF enhanced the expression of MMP‐1 and MMP‐9. These results provide evidence that GM‐CSF has multiple functions enhancing monocytic migration via RhoA and integrin activation, and via MMP expression.
Key molecular events in puromycin aminonucleoside nephrosis rats
Authors: Guan Na , Ding Jie , Deng Jianghong , Zhang Jingjing , Yang Jiyun
Published: September 2004

Nephrin, podocin and α‐actinin are all involved in proteinuria, but it is unclear which molecular event plays a crucial role during the development of proteinuria. Immunofluorescence staining and real‐time quantitative polymerase chain reaction were used to study the glomerular expression of these molecules in puromycin aminonucleoside (PAN) nephrosis. Morphometric methods were applied to evaluate the podocyte foot process (FP) morphology. Two days after PAN injection, nephrin and podocin staining became discontinuous, podocin intensity decreased and FP swelled. Nephrin protein and mRNA decreased at day 5. Both podocin and nephrin intensity decreased dramatically when heavy proteinuria occurred, but nephrin mRNA was regained. When proteinuria disappeared, podocin recovered whereas nephrin did not (P = 0.02); α‐actinin intensity increased (P = 0.009) and the distribution changed. The podocyte FP volume density correlated negatively with nephrin (r = −0.78, P = 0.0001) and podocin immunofluorescence intensity (r = −0.76, P = 0.0001). We conclude that, before the onset of proteinuria, the first response was the nephrin and podocin distribution change, podocin protein decrease and swollen FP; the podocin quantitative change was earlier than nephrin. Podocin and nephrin distribution and the protein level was associated with proteinuria more closely than their mRNA level. The delayed α‐actinin induction might be a reparative response.
Case of acute ileus caused by a spirurina larva
Authors: Miyake Toshihiko , Ikoma Hisami , Hoshima Masakazu , Yamane Etsuo , Hasegawa Hideo , Arizono Naoki
Published: September 2004

A growing body of clinical cases suggests that a kind of nematode larva, type X larva of the suborder Spirurina that inhabits firefly squids (Watasenia scintillans, or ‘Hotaru‐ika’ in Japanese), can cause acute ileus in humans. However, the larva itself has rarely been found in the wall of the obstructed intestine. We describe here a case of acute ileus, in which a type X spirurina larva was found histologically. A 60‐year‐old Japanese man suffered from acute abdomen, and an emergency laparotomy revealed a marked stenosis of the ileum. Histological study of the surgically resected ileum showed severe eosinophilic enteritis and a nematode larva. The morphological features of this larva were identical to those of the type X spirurina larva. Interestingly, the larva that was found existed within a small blood vessel, suggesting that the larva migrans of type X spirurina can take place via vasculature. The patient in the present case did not recall ingesting raw squids prior to the onset of his disease. Hence, this indicates that even if the ingestion of raw firefly squids is uncertain, spirurina infection should be included in the differential diagnosis of acute ileus or eosinophilic enteritis.
Survey of asthma control in Thailand
Authors: BOONSAWAT Watchara , CHAROENPHAN Poonkasem , KIATBOONSRI Sumalee , WONGTIM Somkiat , VIRIYACHAIYO Vilaiwan , POTHIRAT Chaicharn , THANOMSIENG Nikom
Published: September 2004

Objective:  The aim of the study was to determine whether asthma management in Thailand is succeeding in achieving the levels of control, specified in national and international asthma guidelines.

Methodology:  Adults with asthma in Bangkok, Chiang Mai, Songkhla, and Khon Kaen were interviewed, and we have reported on their asthma severity, morbidity, control, perception of asthma, and healthcare use.

Results:  A total of 466 asthma sufferers were interviewed. The burden of asthma was high, with 14.8% of respondents being hospitalized for their asthma in the past year. One‐quarter of those surveyed had lost workdays as a result of their asthma, and most patients felt that their lifestyle was limited. The majority of respondents had intermittent asthma (62.9%), 10.5% had mild persistent asthma, 17.6% had moderate persistent asthma, and 9.0% had severe persistent asthma; increasing severity was significantly associated with increased emergency healthcare use (P < 0.00001). Asthma sufferers greatly underestimated the severity of their condition. Only 36.0% used reliever medication, and use of inhaled corticosteroids was low at 6.7%. Understanding of the inflammatory basis of asthma was poor. Few patients underwent lung function tests or took peak flow meter readings.

Conclusions:  The burden of asthma is high in Thailand, and guidelines are not being followed. Encouraging greater use of inhaled corticosteroids will be an important step towards improving asthma control.
Short‐ and long‐term hospital and community exercise programmes for patients with chronic obstructive pulmonary disease
Authors: ELLIOTT Mercedes , WATSON Carol , WILKINSON Eve , MUSK Arthur W. , LAKE Fiona R.
Published: September 2004

Objective:  Pulmonary rehabilitation in patients with COPD has been shown to be beneficial but the optimal setting is not known. In the present study, the efficacy of a short‐term community‐based exercise programme was compared with a standard hospital outpatient programme. Additionally, the usefulness of community or home programmes in maintaining improvements in the longer term was studied.

Methodology:  Forty‐three patients with moderate to severe COPD were randomized to one of the following three groups: a 3‐month hospital programme then a 9 month home programme (Hospital/Home); a 3‐month hospital programme then a 9‐month community programme (Hospital/Community); or a 12‐month community programme (Community/Community). The initial 3‐month programme was analysed by comparing the Hospital group (Hospital/Home plus Hospital/Community) with the Community group (Community/Community). Six‐minute walking distance (6MWD), quality of life (Guyatt chronic respiratory disease questionnaire, CRQ) and lung function were measured at 0, 3, 6 and 12 months and results were analysed using the Wilcoxon rank sum test.

Results:  At 3 months, there was a significant improvement from baseline in 6MWD in the Hospital group (81.3 ± 18.3 m, P < 0.05, anova) but not the Community group (14.4 ± 28.5 m, not significant). The difference between the groups was not significant (P = 0.058). At 3 months, there was a significant improvement in quality of life in the Hospital group (CRQ +16.3 ± 3.1, P < 0.01, anova) and in the Community group (CRQ +10.2 ± 4.9, P < 0.05, anova) but the difference between the groups was not significant. Following the initial 3‐month programme, the dropout rate was high overall (73% by 12 months), and therefore data from the maintenance programme could not be analysed.

Conclusions:  A 3‐month community‐based exercise programme for patients with COPD did not improve 6MWD. The long‐term retention rates in the programmes were poor.
Molecular epidemiology of tuberculosis and recent developments in understanding the epidemiology of tuberculosis
Authors: NGUYEN Linh N. , GILBERT Gwendolyn L. , MARKS Guy B.
Published: September 2004

Abstract:  The development of molecular typing techniques during the last decade has led to remarkable improvements in epidemiological studies of tuberculosis (TB) and other infectious disease. In this paper, the burden of TB disease, current issues about disease control in developed countries including Australia and the contribution of molecular typing to improved understanding of TB epidemiology are reviewed.
Adult community‐acquired pneumonia in Malaysia: Prediction of mortality from severity assessment on admission
Authors: LOH Li‐Cher , KHOO Sert‐Kim , QUAH Soong‐Yuen , VISVALINGAM Vanitha , RADHAKRISHNAN Anuradha , VIJAYASINGHAM Pillai , THAYAPARAN Tarmizi
Published: September 2004

Objectives:  Prediction of mortality in patients with community‐acquired pneumonia (CAP) can be assessed using clinical severity scores on admission to hospital. The clinical benefit of such tools is untested in Asian countries. The aim of this study was to determine the early adverse prognostic factors in patients hospitalized with CAP in Malaysia and to assess the usefulness of the British Thoracic Society (BTS) severity criteria.

Methodology:  A prospective study was undertaken of all adult patients admitted between August 2002 and March 2003 in an urban‐based university teaching hospital.

Results:  One hundred and eight patients (mean ± SD age 55 ± 20 years; 58% men) were eligible for the study. Thirteen patients (12%) died in hospital and 95 (88%) survived to hospital discharge. Older age, the presence of chronic illness, severity of comorbidity, reduced oxygen saturation and higher blood urea were associated with mortality during admission. Multivariate logistic regression of these variables identified reduced oxygen saturation as the only independently associated variable. BTS criteria fared poorly in predicting mortality compared with clinical assessment by attending clinicians (36‐fold increased risk of death by ‘clinical assessment’ vs two–threefold by ‘BTS criteria’).

Conclusions:  In hospitalized patients with CAP, certain factors are adversely associated with mortality during admission. Severity criteria validated in specific countries might not be universally applicable.
Normal spirometric reference values for Omani children and adolescents
Authors: AL‐RIYAMI Bazdawi M. , AL‐RAWAS Omar A. , HASSAN Mohammed O.
Published: September 2004

Objectives:  Normal lung function has been shown to be population specific. The aim of this study was to derive normal reference spirometric values for Omani children and adolescents.

Methodology:  Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow and forced mid‐expiratory flow were measured in 837 healthy Omani school children aged 6–19 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height and weight for boys and girls separately.

Results:  All measured spirometric parameters increased with age and height and were significantly higher in boys than girls. Height explained the maximum variance for all parameters. After accounting for height in the prediction equations, the contribution of age and weight was minimal. The expiratory ratio (FEV1%FVC) was independent of age and height and its mean values (± standard deviation) were slightly higher in girls (91.1 ± 6.1%) than boys (86.5 ± 7.1%; P < 0.001). The predicted normal values of the subjects using the derived equations were between 5 and 10% lower than the respective values for subjects in Caucasian sample groups.

Conclusion:  The developed prediction equations can be used in clinical practice in Oman and can be considered for use in neighbouring Arab countries.
Association between stress and asthma symptoms: A population‐based study
Authors: OH Yeon‐Mok , KIM Young Sam , YOO Se Hwa , KIM Sung Kyu , KIM Dong Soon
Published: September 2004

Objective:  Although it is believed that stress contributes to asthma, there are no data from studies in the general population to support this belief. To determine whether stress influences asthma in the general population, a database from a nationwide survey to evaluate the relationship between stress and asthma symptoms was used in the present study.

Methodology:  A database generated by the National Health and Nutrition Examination Survey I (in South Korea, 1998) was used for this cross‐sectional study. Stratified random samples of 9263 subjects, aged 20 years or older, were selected from the entire population of the country; 95% of these subjects responded. Among the responders, 5048 subjects aged 20–44 years were included in the study. Subjects were interviewed using a questionnaire. Multivariate analysis was performed using multiple logistic regression.

Results:  The prevalence of wheeze and waking in the night because of cough or shortness of breath in the preceding 12 months was 12.9 and 13.5%, respectively. Multivariate analysis showed that the odds ratios for asthma symptoms increased according to the severity of stress reported by the subjects. When stress levels were classified into four categories of little, some, much and very much stress, the odds ratios for wheeze in the preceding 12 months were 1.7 (95% confidence interval (CI) 1.1, 2.5), 2.6 (95% CI 1.7, 4.0) and 3.6 (95% CI 2.1, 5.9) for subjects reporting some, much and very much stress, respectively, relative to those reporting little stress. Using the same stress‐level classifications, the odds ratios for waking in the night because of cough or shortness of breath in the preceding 12 months were 1.5 (95% CI 1.0, 2.3), 2.4 (95% CI 1.6, 3.6) and 4.0 (95% CI 2.5, 6.4), respectively.

Conclusion:  This cross‐sectional study shows an association between stress and asthma symptoms in the general population of South Korea.