Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy.

Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.

High-fructose diet during adolescent development increases neuroinflammation and depressive-like behavior without exacerbating outcomes after stroke.

Diseases, disorders, and insults of aging are frequently studied in otherwise healthy animal models despite rampant co-morbidities and exposures among the human population. Stressor exposures can increase neuroinflammation and augment the inflammatory response following a challenge. The impact of dietary exposure on baseline neural function and behavior has gained attention; in particular, a diet high in fructose can increase activation of the hypothalamic-pituitary-adrenal axis and alter behavior. The current study considers the implications of a diet high in fructose for neuroinflammation and outcomes following the cerebrovascular challenge of stroke. Ischemic injury may come as a "second hit" to pre-existing metabolic pathology, exacerbating inflammatory and behavioral sequelae. This study assesses the neuroinflammatory consequences of a peri-adolescent high-fructose diet model and assesses the impact of diet-induced metabolic dysfunction on behavioral and neuropathological outcomes after middle cerebral artery occlusion. We demonstrate that consumption of a high-fructose diet initiated during adolescent development increases brain complement expression, elevates plasma TNFα and serum corticosterone, and promotes depressive-like behavior. Despite these adverse effects of diet exposure, peri-adolescent fructose consumption did not exacerbate neurological behaviors or lesion volume after middle cerebral artery occlusion.

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.

The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend® ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.

BACKGROUND: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. HYPOTHESES: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). ANIMALS: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). METHODS: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. RESULTS: Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 µg/dL) compared to lean controls (0.2 ± 0.1 µg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 µg/dL, P = .005) or ID (8.8 ± 10.2 µg/dL, P = .039) than controls (5.0 ± 0.9 µg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 µg/dL; ID: 5.0 ± 4.5 µg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 µg/dL). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.

Lamellar pathology in horses with pituitary pars intermedia dysfunction.

REASONS FOR PERFORMING STUDY: Hoof lamellar pathology in horses with pituitary pars intermedia dysfunction (PPID) has not been described previously. OBJECTIVES: To describe the histomorphometry and pathological lesions in hoof lamellar tissue of animals that had PPID with or without concurrent laminitis, with reference to age-matched controls. We hypothesised that lamellar lesions consistent with laminitis would be associated with PPID, even in animals without current or historical laminitis. STUDY DESIGN: Prospective case-control study. METHODS: Mid-dorsal hoof histological sections were obtained post mortem from the forelimbs of 16 PPID-affected animals either with (n = 6) or without laminitis (n = 10) and 10 age- and breed-matched controls. Sections were examined by a blinded veterinary pathologist. The length and width of 10 primary epidermal lamellae were measured using image analysis software. The morphology and pathology of primary and secondary epidermal lamellae were then typed or graded in axial, middle and abaxial regions. Fasting serum insulin, plasma adrenocorticotropin and blood glucose concentration were measured from blood samples taken prior to euthanasia. RESULTS: All animals with PPID and laminitis had fasting hyperinsulinaemia (median 74.1 miu/l, interquartile range 49.9-349.5 miu/l) whereas PPID animals without laminitis had serum insulin concentrations below the upper limit of the reference range (<20 miu/l). Lamellar pathology in PPID animals with laminitis was variable in severity and unrelated to the reported duration of laminitis (range 2 months-5 years). Most lesions were located abaxially within the lamellar tissue and included increased length and width of the lamellae, chronic abnormal keratinisation, interlamellar epidermal bridging and cell death with more acute lamellar tearing in some cases. The lamellae of PPID animals without laminitis were normal referent to the relevant control group. CONCLUSIONS: Whether PPID and hyperinsulinaemia have a causal inter-relationship or not, it may only be the hyperinsulinaemia that is associated with lamellar morphological alteration and pathology consistent with laminitis.

Oxidative modification, inflammation and amyloid in the normal and diabetic cat pancreas.

The pathogenesis of ß-cell dysfunction leading to pancreatic ß-cell failure seen in type 2 diabetes mellitus is incompletely understood. Pancreatic tissues were collected from nine control cats and nine diabetic cats and labelled immunohistochemically to examine expression of interleukin (IL)-1ß, insulin, islet amyloid polypeptide (IAPP) and 4-hydroxynonenal (4-HNE). Thioflavin-S was used to stain for amyloid. All control cats showed positive labelling for IL-1ß and 4-HNE. Diabetic cats showed varying degrees of inflammation and oxidative modification, owing in large part to the very small amount of islet structure remaining in the typical diabetic cat pancreas. Amyloid deposition was identified in 8/9 diabetic cats and 1/9 control cats. In order to validate these findings, paired biopsy samples taken from an additional group of cats enrolled in a study of obesity and hyperglycaemia (sampling at baseline and after 8-16 weeks of obesity and hyperglycaemia) were labelled for IL-1ß and 4-HNE. A similar pattern of labelling was identified in the baseline samples to that seen in control cats. A significant increase in IL-1ß and 4-HNE expression was seen after a period of hyperglycaemia and obesity. Taken together, these findings suggest that while present in normal cats, markers of inflammation and oxidative modification increase very early during the development of disease. Future studies focusing on these earlier time points are needed to understand the factors that function in protection of the islet ß cell and the development of islet pathology in type 2 diabetes mellitus in the cat.

Cardiotoxicity, inflammation, and immune response after rattlesnake envenomation in the horse.

BACKGROUND: Cardiac abnormalities are reported in rattlesnake-bitten horses. The prevalence and cause are unknown. OBJECTIVES: To detect cardiac damage in rattlesnake-bitten horses by measuring cardiac troponin I (cTnI) and evaluating ECG recordings for presence of arrhythmias, and explore causes of this cardiac damage by measuring venom excretion, anti-venom antibodies, and tumor necrosis factor alpha (TNFα). ANIMALS: A total of 20 adult horses with a clinical diagnosis of rattlesnake bite and 6 healthy adult horses. METHODS: In a prospective clinical study, bite site swabs, blood samples, and urine samples were collected at various time points from 20 horses with a clinical diagnosis of snake bite. Continuous ECG recordings were obtained on the 20 affected horses and 6 normal control horses using 24-hour holter monitors. Plasma samples were assayed for cTnI, serum samples were assayed for TNFα and anti-venom antibodies, and bite site swabs and urine were assayed for venom. RESULTS: Forty percent of rattlesnake-bitten horses (8/20) experienced myocardial damage (increased cTnI). Seventy percent (14/20) experienced a cardiac arrhythmia. There was a positive correlation between cTnI and TNFα (P < .02). Horses with cTnI ≥ 2 ng/mL were more likely to have antibody titers >5,000 (P < .05). No correlations were found between venom concentration and cTnI, anti-venom antibody titers, TNFα, or presence of arrhythmias. CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac abnormalities in this population of horses indicate that cardiac damage after rattlesnake bite is common. Rattlesnake-bitten horses should be monitored for signs of cardiac damage and dysfunction. Long-term follow-up should be encouraged to detect delayed cardiac dysfunction.

Circadian and circannual rhythms of cortisol, ACTH, and α-melanocyte-stimulating hormone in healthy horses.

Cosinor analysis was used to evaluate whether pituitary and adrenal hormones exhibit circadian rhythmicity in horses. The effect of season and animal age on their respective rhythms was also determined. In addition, the usefulness of evaluating cortisol rhythmicity for the diagnosis of pituitary pars intermedia dysfunction (PPID) was assessed. Serum cortisol concentrations (P < 0.01), but not plasma ACTH or α-melanocyte-stimulating hormone (α-MSH), showed a significant circadian periodicity in horses. An effect of season on hormone concentration was observed with plasma ACTH and α-MSH concentration greater in the fall and cortisol concentration greater in the spring (P < 0.001). Age did not affect cortisol rhythm, but it did blunt the variation in cortisol concentration in horses, similar to what has been previously reported to occur in aged people and dogs. In addition, our results suggest that clinically and diagnostically normal, non-PPID-affected horses commonly have a loss of cortisol diurnal rhythm. Therefore, measurement of circadian rhythm is not an appropriate diagnostic test for PPID.

The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses.

BACKGROUND: Plasma α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin (ACTH) concentrations in horses vary with season, confounding diagnostic testing for pituitary pars intermedia dysfunction (PPID). HYPOTHESIS: The goals of this study were to determine whether seasonal variation in plasma α-MSH and ACTH concentrations in horses is influenced by geographic location, breed, or PPID. ANIMALS: Healthy light breed horses residing in Florida, Massachusetts, and Finland (n = 12 per group); healthy Morgan horses (n = 13); healthy ponies (n = 9) and horses with PPID (n = 8). METHODS: Monthly plasma α-MSH and ACTH concentrations were measured by radioimmunoassay. Nonlinear regression analysis was used to estimate the time of peak hormone concentrations. Mean hormone concentrations in fall and nonfall months were compared. RESULTS: The fall peak plasma α-MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α-MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α-MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output.

Neuroendocrine and non-neuroendocrine markers of inflammation associated with performance in endurance horses.

REASONS FOR PERFORMING STUDY: The inflammatory and neuroendocrine response to endurance exercise and relationship of these parameters to performance is not well documented in horses. HYPOTHESES OR OBJECTIVES: Evidence of systemic inflammation is associated with poor performance in horses competing in endurance events. METHODS: Blood was collected prior to and at the finish or elimination point from horses competing in both the 80 and 160 km American Endurance Ride National Championship competitions in 2006. Immunoreactive alpha-melanocyte stimulating hormone (α-MSH) and tumour necrosis factor-alpha (TNF-α) were quantified utilising radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. The concentration of total thiobarbituric acid reactive substances (TBARS) was measured fluorometrically. RESULTS: Thirty horses were included in the study. Endurance exercise was associated with a significant increase in TBARS in the 80 km group but not the 160 km group. TNF-α and α-MSH did not significantly change as a result of exercise in either distance group. Precompetition TBARS was significantly higher in horses that failed to finish the 80 km race, as well as when distances were combined. In addition, precompetition α-MSH was significantly lower in nonfinishers in the 160 km group. Furthermore, competition speed was positively correlated with precompetition α-MSH in the 80 km and negatively correlated with precompetition TNF-α when distances were combined. CONCLUSIONS: Our results suggest that basal oxidative stress markers, circulating cytokines and anti-inflammatory neuroendocrine hormones appear to correlate with endurance performance in horses. POTENTIAL RELEVANCE: Basal oxidative stress markers, circulating cytokines and anti-inflammatory neuroendocrine hormones may be predictive of athletic performance in endurance horses. Future studies evaluating the effect of training on these markers in endurance horses are warranted.

Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction.

BACKGROUND: Equine pituitary pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID. HYPOTHESIS: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses. ANIMALS: Aged horses with PPID, healthy aged-matched controls, and adult controls (n = 14 per group). METHODS: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)-alpha plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-alpha response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA. RESULTS: Aged healthy horses had increased expression of interleukin (IL)-6, IL-8, and interferon-gamma as well as PBMC TNF-alpha release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL-8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age-matched controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Aged horses show evidence of a proinflammatory state that may contribute to development of age-associated diseases. Horses with PPID have increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti-inflammatory hormones.

Coping with occupational stress in an accident and emergency department

Kingston Regional Hospital's Accident and Emergency Department (A&E), located in a volatile area of Kingston, Jamaica, treats 90-170 patients daily. It does so with limited staff and a potentially stressful work environment. This study explores the factors associated with occupational stress in the Department, and the coping strategies used by the doctors and nurses working there. A pre-tested self-administered questionnaire was completed by 28 (84.8) of the total population (n = 33) of health personnel working in the A&E. The participants were 15 (53.6) doctors, eight (28.6) registered nurses and five (17.8) enrolled assistant nurses. The data were analyzed using Statistical Package for the Social Sciences (SPSS) Version 7.5. Qualitative data were analyzed by sorting texts into related themes and describing the ideas of the subjects. The median age was 32 years, range 23-50 years. Median duration of employment in the A&E was three years, range 0.5-22 years. Eighteen (60) rated the A&E as [quot ]stressful[quot ]. The major sources of stress were the external environment and the amount and quality of the workload. Ninety-six per cent reported experiencing one to seven emotional and physical symptoms. Forty-six per cent also reported behavioural symptoms. The emotional, physical and behavioural symptoms of stress were associated (p < 0.05). The number of behavioural symptoms experienced was associated with age (p < 0.05). The majority (89.2) of doctors and nurses reported that they were satisfied with their jobs and had no intention of leaving their jobs within a year. This suggested the effectiveness of the reported humour, teamwork and [quot ]extracurricular[quot ] activities in buffering the effects of stress. Nurses were more likely to be [quot ]burned out[quot ] than doctors (p = 0.03). The respondents suggested increased monetary compensation, more staff and positive feedback from managers as factors which may relieve work stress. They suggested that organized counselling and stress management programmes would be useful

Differences in mortality between patients attending the emergency room services for asthma and chronic obstructive pulmonary disease.

Asthma has a more favourable prognosis than chronic obstructive pulmonary disease (COPD), based on studies including few asthmatics and few women with COPD. We assessed differences in mortality between people attending the emergency room for asthma and for COPD in a population-based cohort. We recruited all the men and women, who were residents of Barcelona (Spain) over 14 years of age, who attended emergency room services for an obstructive lung disease during the period 1985-1989. Vital status was followed up to the end of 1995. A total of 15,517 individuals (including 4555 asthmatics and 2194 females with COPD) were studied. Mortality was ascertained using a record linkage with the regional Mortality Registry. Overall, 43.6% people died during the follow-up period. Mortality was higher among individuals with COPD than with asthma, in males and females, for all causes of death, as well as for cancer, cardiovascular and respiratory causes. After adjusting for age, the relative risk (RR) of dying of a male attending for COPD and discharged home was 1.50 (1.29-1.74) in comparison with a male attending for asthma, and 3.06 (2.66-3.51) for a male attending for COPD and admitted into the hospital. Similar figures were found for females. The increased risk for patients with COPD was significantly higher than for asthma in all age groups. Both males and females with asthma have a more favourable prognosis than patients with COPD, for all age groups.

Sex differences in mortality of people who visited emergency rooms for asthma and chronic obstructive pulmonary disease.

We assess the sex differences in mortality in a population-based cohort of those Barcelona residents older than 14 yr of age who received emergency room services (ERS) for either chronic obstructive pulmonary disease (COPD) or asthma, during the period from 1985 to 1989. Vital status was followed to the end of 1995. A total of 15,517 individuals, 9,918 males and 5,599 females were included in the study. Asthma was diagnosed in 16% of males and 53% of females. Overall, 50% of males and 30% of females died during the follow-up period. The mortality rates in both males and females who visited emergency rooms for COPD or asthma were significantly higher than the expected rates in the general population. These relative increases in the mortality rates were significantly higher in females than in males for both causes of death, COPD (age-adjusted female/male ratio = 2.39), and asthma (ratio = 3.95). However, survival was better in females than males among individuals in the study. The higher fatality in males than females was observed for all causes of death, all respiratory causes, and COPD (risk ratio among patients with COPD = 0.42, 0.29-0.59, and among patients with asthma = 0.11, 0.02-0.60), but not for asthma. Mortality for asthma was higher in females with a diagnosis of COPD (2.79, 1.52-5.13), but it was not different among individuals in whom asthma was diagnosed (1.02, 0.56-1.87). Greater severity of COPD in males than in females could explain a higher risk of dying for all respiratory causes and COPD in males. The increased risk of asthma death in females may be due to problems of coding the term "asthma" in death certificates. The higher rates in females than in males when comparing with the general population, may be an expression of a greater similarity in risk factors, such as smoking, in our population than in males and females of the general population.

The association between the oculocardiac reflex and post-operative vomiting in children undergoing strabismus surgery.

The oculocardiac reflex (OCR) is a potentially serious complication of ophthalmic surgery which is most commonly elicited during paediatric strabismus surgery. Post-operative vomiting (POV) is also extremely common after such procedures and may result in admission following planned day-case surgery. Although many factors play a part in the occurrence of POV, stimulation of the trigemino-vagal reflex arc is thought to explain the particularly high rate of vomiting after strabismus surgery. The OCR and the vaso-vagal response share this neuronal pathway, the bradycardia of the OCR often being the only objective feature of the vaso-vagal response while the patient is anaesthetised. The aim of this study was to investigate the possible association between the occurrence of the OCR and subsequent POV in children undergoing strabismus surgery. We have studied this relationship in 79 children, aged between 1 and 13 years, undergoing strabismus surgery under standardised anaesthetic conditions. A positive OCR was regarded as a drop in heart rate of 10% or more, or the onset of a dysrhythmia. An intraoperative OCR was elicited in 51 (64.6%) of the 79 children, whilst 29 (36.7%) developed POV in the subsequent 24 h period. There was a significant association between a positive intraoperative OCR and POV (p = 0.01): children with a positive OCR were 2.6 times more likely to vomit than those without the reflex. We conclude that there is an association between the occurrence of the OCR and POV and discuss possible preventive strategies.

Reproducibility of DNA ploidy and S-phase values from paraffin-embedded tissue.

OBJECTIVE: To determine the degree of variability of DNA flow cytometric results between two types of flow cytometers. STUDY DESIGN: Single-cell suspensions were made from 40 paraffin blocks of ovarian carcinoma using a modified Hedley procedure. These samples were consecutively analyzed in both Coulter's Profile II and Elite Flow cytometers. Gated and ungated data were collected and analyzed using Phoenix flow system's multicycle software. RESULTS: There were 16 (40%) DNA diploid, 23 (58%) DNA aneuploid and 1 DNA tetraploid tumor. The degree of variability in the DNA index coefficient of variation of the G0/G1 diploid peak, percentage of S phase, percentage of G2M, percentage of debris plus percentage of clumps were compared. Excellent correlations of the results were obtained in the DNA index (r = .999) and in percentage of S phase (r = .946). CONCLUSION: It is feasible to standardize variables of flow cytometric instruments to obtain reproducible results.

Cohort study on cancer mortality among workers in the pulp and paper industry in Catalonia, Spain.

We examined mortality in a retrospective follow-up study of 3,241 workers employed between 1970-1992, in four pulp and paper mills in Catalonia, Spain. Vital status was determined for 95% of the cohort. Exposure was reconstructed using job histories and a company exposure questionnaire. Standardized mortality ratios (SMR) were derived using mortality rates of Spain as the reference. For all workers, mortality from all causes (SMR = 76; 95%; confidence intervals [CI] = 65-88; 189 deaths) and all malignant neoplasms (SMR = 93; CI = 72-119; 65 deaths) were less than the expected. Excess risk was observed for mortality from all neoplasms in females (SMR = 168; CI = 84-303; 11 deaths), for large intestine cancer in both sexes (SMR = 250; CI = 115-525; 8 deaths), particularly after 10 years of employment and latency (SMR = 355; CI = 154-701; 8 deaths), and for breast cancer in females (SMR = 286; CI = 77-732; 4 deaths). These findings suggest that workers employed in the pulp and paper industry may have an excess risk of specific cancers.

Fluoride supplementation status, fractures and osteopenia in children with acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) experience fractures on the basis of osteopenia related to chemotherapy administered for the maintenance of remission. It is likely that corticosteroids are the main cause of bone mineral loss in this circumstance. Because fluoride has been used as a therapeutic intervention in osteoporosis, including that induced by corticosteroid therapy, we explored the prospect that children with ALL who received fluoride supplementation (in drinking water or from other sources) may be relatively protected from iatrogenic skeletal morbidity. Children who completed therapy according to the Dana Farber Cancer Institute protocol 87-01 (n=35) were assessed by skeletal radiology and bone densitometry every 6 months from diagnosis. In addition, their families completed a questionnaire relating to fluoride supplementation. There was no correlation between such fluoride supplementation and either the prevalence of fractures or the severity of osteopenia. This outcome may reflect the mainly appendicular location of the fractures in this group of children. These findings, together with a consideration of the risk benefit ratio of fluoride administration to children at large, suggest that such intervention is unlikely to be beneficial in limiting skeletal morbidity during the treatment of ALL in childhood.

FTIR spectroscopy study of PTHrP(1-34) involved in humoral hypercalcaemia of malignancy.

The components of secondary structure of the biologically-active N-terminal domain of human parathyroid-hormone-related protein (residues 1-34) and several truncated species were examined using Fourier transform infrared (FTIR) spectroscopy. The major structural features include a segment of alpha-helix within the N-terminal segment probably extending from Glu-4 to Lys-11 with three beta-turns localized to the segments Gly-12 to Ile-15, Gln-16 to Arg-20 and His-25 to Ala-29. Some beta-sheet was detected in the full-length peptide, but not in any of the C-terminal truncated samples. These structural features were studied in the smaller peptides for the purpose of localization of the various components and with a view to describing the region likely to form the bulk of the receptor binding site.