The Prevalence of Respiratory Symptoms in Irish Dairy Farmers.

Work-related respiratory disease is a significant risk in the farming community. We assessed respiratory symptoms using a validated work-related respiratory questionnaire in 126 dairy farmers (19-75 years; 91.3% male). The prevalence of cough symptoms was 34.4%. Thirty-seven farmers (29.4%) complained of upper airway symptoms while forty (31.7%) complained of eye problems. Cumulated symptoms scores did not indicate higher than normal rates of chronic lung disease. Only 10 farmers (7.9%) were taking medication for lung conditions. Only 7 (5.6%) were current smokers. The rate of respiratory symptoms did not relate to the herd size or the method of animal feeding used by the farmers. The incidence of respiratory symptoms remains high among Irish dairy farmers. While the exact reason for this is unknown it may be related to continuing work- related dust exposure.

SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans.

Methylation of the SKA2 (spindle and kinetochore-associated complex subunit 2) gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness and psychiatric phenotypes linked to suicide in trauma-exposed veterans. About 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. Of all, 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the cytosine-guanine locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated single nucleotide polymorphism (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD) and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylation(adj)). Specifically, DNA methylation(adj) was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylation(adj) and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylation(adj) of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

The prevalence of respiratory symptoms among mushroom workers in Ireland.

BACKGROUND: Respiratory conditions such as asthma, bronchitis, hypersensitivity pneumonitis and upper airways symptoms have been ascribed to fungal exposures. Mushroom workers may be at risk of these as a consequence. AIMS: To assess the prevalence of respiratory symptoms in mushroom workers. METHODS: A cross-sectional study assessed 4 weeks of respiratory symptoms among mushroom workers divided into four categories of exposure, using a self-administered respiratory questionnaire and spirometry. RESULTS: The population of 191 subjects was predominantly (66%) from Eastern Europe; 61% were women and 39% were under 30. It included 73 growers, 38 composters, 26 administrators and 52 packers. Among all workers, there was a high prevalence (67%) of one or more respiratory symptoms which did not appear to vary by age, gender, pack-years of smoking or duration of employment. There was a significant improvement in respiratory symptoms in workers during absence from the workplace (P < 0.001). Spirometry readings across all groups were within normal values. Symptom profiles suggest that as many as 22 workers had symptoms of airways disease; 18 (82%) of these were mushroom growers. Growers were significantly more likely to have symptoms consistent with airways disease than all other workers, odds ratio 9.2 (95% CI 3.0-28.4). CONCLUSIONS: There was a high prevalence of respiratory symptoms among mushroom workers. Mushroom growers may be at high risk of airways disease, possibly from fungal antigens or related exposures.

Metabolic rates, genetic constraints, and the evolution of endothermy.

The metabolic distinction between endotherms and ectotherms is profound. Whereas the ecology of metabolic rates is well studied, how endotherms evolved from their ectothermic ancestors remains unclear. The aerobic capacity model postulates that a genetic constraint between resting and maximal metabolism was essential for the evolution of endothermy. Using the multivariate breeders' equation, I illustrate how the (i) relative sizes of genetic variances and (ii) relative magnitudes of selection gradients for resting and maximal metabolism affect the genetic correlation needed for endothermy to have evolved via a correlated response to selection. If genetic variances in existing populations are representative of ancestral conditions, then the aerobic capacity model is viable even if the genetic correlation was modest. The analyses reveal how contemporary data on selection and genetic architecture can be used to test hypotheses about the evolution of endothermy, and they show the benefits of explicitly linking physiology and quantitative genetic theory.

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury.

The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

The quantitative genetics of maximal and basal rates of oxygen consumption in mice.

A positive genetic correlation between basal metabolic rate (BMR) and maximal (VO(2)max) rate of oxygen consumption is a key assumption of the aerobic capacity model for the evolution of endothermy. We estimated the genetic (V(A), additive, and V(D), dominance), prenatal (V(N)), and postnatal common environmental (V(C)) contributions to individual differences in metabolic rates and body mass for a genetically heterogeneous laboratory strain of house mice (Mus domesticus). Our breeding design did not allow the simultaneous estimation of V(D) and V(N). Regardless of whether V(D) or V(N) was assumed, estimates of V(A) were negative under the full models. Hence, we fitted reduced models (e.g., V(A) + V(N) + V(E) or V(A) + V(E)) and obtained new variance estimates. For reduced models, narrow-sense heritability (h(2)(N)) for BMR was <0.1, but estimates of h(2)(N) for VO(2)max were higher. When estimated with the V(A) + V(E) model, the additive genetic covariance between VO(2)max and BMR was positive and statistically different from zero. This result offers tentative support for the aerobic capacity model for the evolution of vertebrate energetics. However, constraints imposed on the genetic model may cause our estimates of additive variance and covariance to be biased, so our results should be interpreted with caution and tested via selection experiments.

Isochromosome of a deleted 20q: a rare but recurrent chromosome abnormality in myelodysplastic syndromes.

Interstitial deletion of the long arm of chromosome 20, as the sole abnormality, is commonly observed in myeloid malignancies, including myeloproliferative disorder, myelodysplastic syndrome, and acute myeloid leukemia. The breakpoints of the deletion are typically located in the region 20q11.2 approximately q13.3, although smaller deletions within this region have also been reported. We present here 4 patients with myelodysplastic syndrome with an isochromosome of the deleted long arm of chromosome 20: ider(20)(q10)del(20)(q11q13). Fluorescence in situ hybridization studies were performed on the bone marrow samples from these patients to prove the identity of this unusual chromosome abnormality.

Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea-pigs.

1. We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2. Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4. Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5. These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only.

Three cases of paradoxical vocal cord adduction followed up over a 10-year period.

Paradoxical vocal cord adduction (PVCA) is a rare disorder that may present with symptoms similar to asthma. Incorrect diagnosis may result in patients being unwittingly treated with prolonged high doses of antiasthma medication. PVCA probably forms part of a spectrum of uncommon and complex breathing disorders related to laryngeal dysfunction. Herein, we describe three cases of PVCA that illustrate the spectrum of clinical and physiologic presentation and the long-term natural history over a 10-year follow-up period. We conclude that PVCA, contrary to previous reports, is not always a benign condition; it may feature marked hypoxemia, fail to respond to previously advocated therapeutic strategies, and can persist on a long-term basis.

Familial cryptogenic fibrosing pleuritis with Fanconi's syndrome (renal tubular acidosis). A new syndrome.

We describe two siblings with a progressive unrelenting and unique syndrome of bilateral fibrosing pleuritis of unknown cause occurring in association with Fanconi's syndrome (renal tubular acidosis). The parents of the siblings were second cousins. Both siblings had identical pleural histologic characteristics and identical urinary metabolic defects. This condition resulted in the development of severe respiratory failure in both patients and ultimately the death of the older sibling at the age of 21 years.

Neurogenic goblet cell secretion and bronchoconstriction in guinea pigs sensitised to trimellitic anhydride.

Trimellitic anhydride is a cause of occupational asthma in humans. We have previously found that tracheal instillation of trimellitic anhydride conjugated to guinea pig serum albumin induces acute bronchoconstriction and airway plasma exudation in sensitised animals, responses mediated primarily via histamine release. In the present study, neural mechanisms mediating bronchoconstriction and goblet cell secretion were determined in trimellitic anhydride-sensitised guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent reflex mechanisms, pretreatment with capsaicin to eliminate afferent mechanisms, or cimetidine and mepyramine to eliminate histamine-mediated mechanisms. The magnitude of secretion of intracellular mucus from tracheal goblet cells was quantified morphometrically as a mucus score which is inversely related to the degree of discharge. Guinea pigs were injected intradermally either with 0.1 ml 0.3% trimellitic anhydride in corn oil or with corn oil alone as control. Fourteen to eighteen days later all sensitised animals had developed specific immunoglobulin (Ig) G1 antibodies whereas the controls had not. Tracheal instillation of conjugated trimellitic anhydride in anaesthetised animals significantly increased airway lung resistance (RL) 24-fold in sensitised guinea pigs (34.3 +/- 7.9 cm H2O.ml-1.s) compared with controls (1.4 +/- 0.1 cm H2O.ml-1.s). Mucus score was significantly reduced by 51% (indicating goblet cell secretion) in sensitised guinea pigs (183 +/- 22 mucus score units) compared with controls (372 +/- 41 mucus score units). The antihistamines significantly inhibited conjugated trimellitic anhydride-induced bronchoconstriction by 89%, but did not significantly affect goblet cell discharge. Hexamethonium alone did not significantly affect conjugated trimellitic anhydride-induced bronchoconstriction or goblet cell secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Tube graft replacement of abdominal aortic aneurysm.

In the 16 year period ending December 1985, 332 patients underwent elective abdominal aortic aneurysm replacement. One hundred fifty-four (46 percent) of these patients had tube graft replacement of the aneurysm. Patients were selected for tube graft on the basis of physical, angiographic, and intraoperative examinations. There were 123 mean and 31 women, with a mean age of 68 years. Complete follow-up ranging from 1 to 168 months (mean 53 months) was obtained in 137 of the surviving patients (87 percent). Two patients required revision to a bifurcated graft; one for iliac stenosis and one for iliac thrombosis. No iliac aneurysms were seen and no other aortoiliac complications were evident. Five other patients required femoro-distal reconstruction for either occlusive disease (three patients) or aneurysmal disease (two patients) at the groin or below. Life table analysis showed a 5 year survival rate of 65 percent and a 7 year rate of 54 percent. Conclusions drawn from this study reconfirm that in carefully selected patients, tube graft replacement of abdominal aortic aneurysm is an enduring procedure with few complications developing due to progression of iliac occlusive or aneurysmal disease.

Atherosclerosis in the younger patient. Results of surgical management.

One hundred fifty-three patients under 50 years of age with atherosclerosis were studied. Hospital and office records were reviewed to determine risk factors, operations performed, postoperative course, and long-term results. These data were then compared with the data in the group of patients over 50 years of age. Results of this study indicate that survival in the younger patient is better than that in the patient over 50. Survival in the younger patient compared favorably to that in the general population through 5 years. Limb salvage rates after aortofemoral bypass and femoropopliteal bypass in both age groups were the same; however, limb salvage after femorotibial bypass in patients under 50 was not as good as in the older patient. Based on these results, the disease process in patients under 50 years of age does not appear more virulent than in those over 50 years of age. Smoking is the most significant risk factor in patients under 50 with atherosclerotic peripheral vascular disease.

Aortobrachiocephalic reconstruction.

Aortobrachiocephalic reconstruction was studied in 26 patients. Nine had suffered a previous stroke, and seven had residual deficity. A previous carotid endarterectomy or carotid-to-subclavian bypass had been performed in eight patients. The ascending aorta was the proximal anastomotic site in all cases. Bypass grafting to a single distal site was performed in 11 patients (42 percent), to 2 distal sites in 14 patients (54 percent) and to 3 distal sites in 1 patient (4 percent). The carotid artery, innominate arteries, or both were involved in all reconstructions. Concomitant carotid or subclavian endarterectomy was performed in 14 patients, 1 of whom also had a coronary bypass at the same time. Two patients (7 percent) died in the postoperative period. Twenty-three of 24 survivors (96 percent) had relief of symptoms after operation. Only one patient had worsening of symptoms postoperatively, which was secondary to intracerebral hemorrhage. Results of this study indicate that direct revascularization of the arch branches can be carried out with minimal morbidity and mortality. Relief of presenting symptoms is to be expected, and long-term results suggest that the operation is durable.

Effect of a failed distal reconstruction on the level of amputation.

Controversy exists as to whether the level of amputation is adversely affected by an unsuccessful limb salvage attempt. Two hundred ten amputations following failed reconstruction attempts in 191 patients were studied and compared with 551 amputations in limbs with no prior revascularization. Initially, 147 of those with failed reconstruction attempts underwent below-knee (BK) amputation and 63 underwent above-knee (AK) amputation. One hundred ten of 143 (77%) surviving BK amputations eventually healed. This is in contrast to the eventual healing in 266 of 298 (89%) of the BK amputations performed with no prior attempts at reconstruction. A statistically significant (p less than 0.05) difference in eventual healing favoring those with no prior reconstruction was demonstrated. Successful reconstruction of the ischemic extremity is the goal of vascular surgery and should be attempted when indicated. However, it should be realized that unsuccessful revascularization attempts may adversely affect healing in those limbs initially considered for a BK amputation.

Prospective randomized study of concomitant lumbar sympathectomy with aortoiliac reconstruction.

Ninety-three consecutive patients for aortofemoral bypass grafting were studied to determine the effect of sympathectomy on early and late patency, the need for subsequent distal procedures, amputation rate, and ankle-brachial Doppler systolic pressure indexes. Sixty-seven patients completed the study. Fifty-three limbs were randomized to receive sympathectomy and 81 no sympathectomy. The mean length of follow-up postoperatively was 11 +/- 2.53 months (maximum 24). Five grafts occluded, two early and three late. Both early occlusions occurred in the nonsympathectomy group and all three late occlusions ensued in the sympathectomy group. Subsequent distal procedures were necessary early (within 30 days) in five limbs, all in the nonsympathectomy group. Nine limbs required distal procedures late, four (5 percent) in the nonsympathectomy group and five (9.5 percent) in the sympathectomy group (p greater than 0.05). Altogether, distal bypass was required in 11 percent of the patients in the nonsympathectomy group versus 9.4 percent in the sympathectomy group (p greater than 0.05). Five limbs were amputated 4 to 14 months after aortofemoral bypass, four (5 percent) in the nonsympathectomy and one (2 percent) in the sympathectomy group (p greater than 0.05). The ankle-brachial pressure index increased significantly after aortofemoral bypass in both groups (p less than 0.05). The mean increase after aortofemoral bypass was more marked in the sympathectomy group (p greater than 0.05). Thus, at a mean follow-up time of 11 months after aortofemoral bypass, there was no significant difference in graft patency, need for subsequent distal bypass, or amputation rate between the sympathectomy and nonsympathectomy groups.

Screening for cholelithiasis prior to aortic reconstruction.

A study was undertaken to determine the value of preoperative oral cholecystography and the incidence and complications of cholelithiasis in patients undergoing aortic reconstruction. Over an 11-year period, 785 patients underwent aortic reconstruction. Forty-seven had a previous cholecystectomy; of the 738 remaining patients, 394 underwent preoperative operative oral cholecystography to screen for cholelithiasis. Seventy-three (18 percent) were found to have gallbladder disease. Thirteen had symptoms attributed to cholelithiasis and underwent cholecystectomy with aortic reconstruction. Three hundred eighty-one were left with the gallbladder after aortic reconstruction, 60 in whom disease was identified and 321 with normal oral cholecystography results. Three patients developed cholecystitis in the postoperative period, one in the diseased group and two with normal gallbladders. The incidence of postoperative cholecystitis was 0.8 percent (3 patients). Preoperative oral cholecystography is of little value as a screening tool. Cholecystectomy during aortic reconstruction is probably safe and the risk of postoperative cholecystitis in the asymptomatic patient is negligible.

Effects of dietary quality on basal metabolic rate and internal morphology of European starlings (Sturnus vulgaris).

European starlings (Sturnus vulgaris) were fed either a low- or high-quality diet to test the effects of dietary quality on basal metabolic rate (BMR) and internal morphology. Basal metabolic rate did not differ significantly between the two dietary groups, but internal morphology differed greatly. Starlings fed the low-quality diet had heavier gastrointestinal tracts, gizzards, and livers. Starlings fed the high-quality diet had heavier breast muscles. Starlings on the low-quality diet maintained mass, while starlings on the high-quality diet gained mass. Dry matter digestibility and energy digestibility were lower for starlings fed the low-quality diet, and their food and water intake were greater than starlings on the high-quality diet. The lack of dietary effect on BMR may be the result of increased energy expenditure of digestive organs paralleling a reduction of energy expenditure of organs and tissues not related to digestion (i.e., skeletal muscle). This trade-off in energy allocation among organs suggests a mechanism by which organisms may alter BMR in response to a change in seasonal variation in food availability.