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Biomedical subjects

R Harley

Publications and source records attributed to R Harley.

At least 19 recordsLinked to original sources

Postanaesthetic tracheal strictures in three rabbits.

Within an 11-day period, three rabbits were anaesthetized for neutering. All were endotracheally intubated with 12 cm long, 2.5 mm (inner diameter [ID]) polyvinylchloride (PVC) tubes. All rabbits developed clinical signs of dyspnoea and upper respiratory tract obstruction, 17-21 days later. One rabbit was found dead; the other two were treated, but one was euthanized and one died. At necropsy examination, focal chronic inflammation and significant localized narrowing of the tracheal lumen was found in all cases. The affected sites corresponded to the position of the bevel of the endotracheal tube (ETT) during anaesthesia. Histopathology could not differentiate between a traumatic or chemical cause for the narrowing. Possible causes include trauma by the bevel of the ETT when turning the rabbit or preparing the surgical site or a chemical burn from incorrect disinfection or inadequate rinsing of the tubes. Iatrogenic tracheitis should be considered as a cause of dyspnoea, when clinical signs arise 2-3 weeks after anaesthesia.

Anesthesia, Endotracheal↗

Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression.

BACKGROUND: Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings. METHOD: This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5-10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life. RESULTS: Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30.7 (S.D. = 73.7) months versus 13.5 (S.D. = 13.2) months; p=0.001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity. CONCLUSIONS: PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice.

Adolescent↗

Continuation cognitive-behavioural therapy maintains attributional style improvement in depressed patients responding acutely to fluoxetine.

BACKGROUND: Little is known about how continuation and maintenance cognitive-behavioural therapy (CBT) influences important psychological constructs that may be associated with long-term outcome of major depressive disorder. The goal of this study was to examine whether CBT would help maintain attributional style changes experienced by patients during acute phase fluoxetine treatment. METHOD: Three hundred and ninety-one patients with major depressive disorder were enrolled in an open, fixed-dose 8 week fluoxetine trial. Remitters to this acute phase treatment (N= 132) were randomized to receive either fixed-dose fluoxetine (meds only) or fixed-dose fluoxetine plus cognitive-behavioural therapy (CBT+meds) during a 6-month continuation treatment phase. The Attributional Style Questionnaire (ASQ) was completed by patients at three time points - acute phase baseline, continuation phase baseline and continuation phase endpoint. Analysis of covariance was used to compare continuation phase ASQ composite score changes between groups. RESULTS: Patients in both treatment groups experienced significant gains in positive attributional style during the acute phase of treatment. Continuation phase ASQ composite change scores differed significantly between treatment groups, with the CBT + meds group maintaining acute phase positive attributional style changes, and the meds only group exhibiting a worsening of attributional style. The two treatment groups did not significantly differ in rates of relapse and final continuation phase visit HAMD-17 scores. CONCLUSIONS: In this sample, the addition of CBT to continuation psychopharmacological treatment was associated with maintenance of acute treatment phase attributional style gains. Further research is needed to evaluate the role of such gains in the long-term course of depressive illness.

Adult↗

Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls.

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.

Adolescent↗

Salivary and serum immunoglobulin levels in cats with chronic gingivostomatitis.

The salivary and serum concentrations of immunoglobulins G, M and A (IgG, IgM and IgA), and the salivary concentrations of albumin were measured by ELISA in 30 cats with chronic gingivostomatitis and 32 healthy cats. The cats with chronic gingivostomatitis had significantly higher salivary concentrations of IgG, IgM and albumin, and higher serum concentrations of IgG, IgM and IgA, but significantly lower salivary concentrations of IgA than the healthy cats. The cats with chronic gingivostomatitis were treated with either methylprednisolone, sodium aurothiomalate, metronidazole and spiramycin, or oral hygiene products. After three months of treatment, the cats receiving methylprednisolone had a significant reduction in serum IgG levels compared to the cats treated with sodium aurothiomalate or metronidazole and spiramycin, but after six months of treatment there were no significant differences between the groups. Before the treatments, the levels of oral inflammation were not correlated significantly with any of the serum or salivary immunoglobulin levels. However, the changes in oral inflammation were correlated significantly with the changes in the salivary IgM concentration after three and six months of treatment, and with the change in the salivary IgA concentration after six months of treatment.

Animals↗

Left ventricular myxosarcoma in a dog.

An entire male Neopolitan mastiff, aged two years and eight months, presented with a history of chronic diarrhoea and weight loss. The diarrhoea had been present for approximately 12 months and had progressively worsened, with weight loss developing over an eight-week period prior to presentation. No primary gastrointestinal or metabolic cause for the diarrhoea could be identified. Echocardiography revealed a large, multilocular, cyst-like structure within the pericardium compressing the heart and displacing it to the right. The mass was surgically excised from the left ventricular myocardium. Histopathological examination showed it to be a low-grade malignant myxosarcoma. The dog made a full recovery and was still clinically normal nine months postoperatively, with no evidence of tumour recurrence or metastases. However, 11 months postsurgery, the clinical signs of diarrhoea and weight loss returned. Tumour recurrence with local metastasis was diagnosed and the dog was euthanased 358 days after the original surgery.

Animals↗

Health-related quality of life in Persian Gulf War Veterans.

OBJECTIVE: The objective of this investigation is to describe the health-related quality of life of Persian Gulf War (GW) veterans and to examine the effects of current chronic medical conditions and psychiatric status on physical functioning. METHODS: To measure health-related quality of life, the Medical Outcomes Short Form Survey (SF36) was administered approximately 4 years after the GW to a stratified, random sample of New England-area GW-deployed veterans and a group of military personnel deployed to Germany during the GW. The SF36 scores for the GW-deployed study population (N = 141) were compared with those for the Germany-deployed group (N = 46) and with published U.S. population norms. Multiple linear regression analyses were performed to identify risk factors associated with lower physical health functioning in the GW-deployed study group. RESULTS: Functional health status was significantly lower in the GW-deployed group compared with the Germany-deployed group for each of the SF36 subscales and the two summary scores (Physical Component Summary [PCS] and Mental Component Summary). Compared with the general U.S. population, the GW-deployed group median was between the 25th and 50th percentile for the Physical Functioning subscale and the PCS score. Within the GW-deployed group, lower education, psychological symptomatology, and a higher number of chronic self-reported medical conditions were significant predictors of the PCS score. CONCLUSION: GW-deployed veterans report lower functional health status compared with a group of Germany-deployed veterans and published general U.S. population norms. Within the group of GW-deployed veterans, several current medical and psychological conditions predictive of lower physical functioning levels were identified.

Adult↗

Lifetime prevalence of mood and anxiety disorders in twin pairs discordant for schizophrenia.

There have been long questions about the relationship of schizophrenia to other mental disorders. Lifetime DSM-III-R diagnoses of mood and anxiety disorders in twins with clinically diagnosed schizophrenia (n = 24) and their non-affected co-twins (n = 24) were compared with twins from pairs without schizophrenia (n = 3327) using a sample from the Vietnam Era Twin Registry. Schizophrenic probands had significantly elevated rates of all included disorders (bipolar disorder, major depression, dysthymia, generalized anxiety disorder, panic disorder, and PTSD) compared with controls (P<0.01). The odd ratios comparing co-twins of schizophrenic probands with controls was greater than three for every disorder, but did not attain statistical significance. A similar pattern was observed when analyses were restricted to only monozygotic twins (n = 12). Consistent with other studies, schizophrenics appeared to have higher rates of a range of mental disorders. Our results suggest that schizophrenia per se represents a risk factor for other psychiatric disorders, but the absence of significantly elevated risk among non-schizophrenic co-twins suggested that family environmental and/or genetic factors that contribute to risk of schizophrenia do not increase the risk of mood and anxiety disorders to the same extent that the risk of these other disorders is increased by the presence of schizophrenia.

Adult↗

Cytokine mRNA expression in lesions in cats with chronic gingivostomatitis.

Semiquantitative reverse transcription-PCR assays were developed to measure feline interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, and IL-12 (p35 & p40); gamma interferon (IFN-gamma); and glyceraldehyde-3-phosphate dehydrogenase mRNA concentrations in biopsies of feline oral mucosa. Biopsies were collected from 30 cats with chronic gingivostomatitis (diseased) prior to each cat receiving one of four treatments. In 23 cases replicate biopsies were collected 3 months after treatment commenced. Biopsies were also analyzed from 11 cats without clinical disease (nondiseased). Expression of IL-2, IL-10, IL-12 (p35 and p40), and IFN-gamma was detected in most nondiseased biopsies, while IL-6 was detected in a minority, and IL-4 and IL-5 were both undetectable. Compared to nondiseased cats, the diseased population showed a significant increase in the relative mRNA expression of IL-2, IL-4, IL-6, IL-10, IL-12 (p35 and p40), and IFN-gamma. In contrast, IL-5 mRNA expression was unchanged and was only detected in one case. No significant relationship was demonstrable between the change in relative expression of specific cytokine mRNA and the change in clinical severity of the local mucosal lesions over the treatment period. The results demonstrate that the normal feline oral mucosa is biased towards a predominantly (Th) type 1 profile of cytokine expression and that during the development of lesions seen in feline chronic gingivostomatitis there is a shift in the cytokine profile from a type 1 to a mixed type 1 and type 2 response.

Animals↗

Determination of salivary and serum immunoglobulin concentrations in the cat.

The concentrations of immunoglobulin(Ig)G, IgM, and IgA were determined in unstimulated saliva (n=14), stimulated saliva (n=6), and serum (n=14) from healthy adult cats. Analysis by single radial immunodiffusion (SRID) was compared with class-specific enzyme linked immunoassays (ELISA), and good correlation was demonstrated between the two techniques. Mean (s.d.) serum concentrations of 19.08 (5.38) mg/ml IgG, 2.04 (0.83) mg/ml IgM and 2.6 (2.16) mg/ml IgA were obtained by SRID. The immunoglobulin concentrations of the saliva samples frequently fell below the quantification limits for SRID, however, all samples could be quantified by ELISA making this the method of choice for the determination of salivary immunoglobulin concentrations. IgA was the predominant class of immunoglobulin secreted by the major feline salivary glands, and the concentration of each immunoglobulin class was greater in unstimulated versus stimulated saliva. Analysis of sequential unstimulated saliva samples collected each morning and evening over a 4-day period from four cats revealed the salivary immunoglobulin concentrations to be relatively constant.

Animals↗

Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.

OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.

Asbestos, Serpentine↗

The spectrum of adult adenovirus pneumonia.

Adenovirus pneumonia is endemic among infants and children. We report an adult case of adenovirus pneumonia causing respiratory failure and infection in the patient's spouse. The case in the spouse presented as an exacerbation of COPD.

Adenovirus Infections, Human↗

Transforming growth factor-beta 1 and collagen gene expression during postnatal skin development and fibrosis in the tight-skin mouse.

BACKGROUND: The tight-skin (Tsk) mutation in the mouse leads to widespread connective tissue abnormalities characterized by excessive collagen deposition that is similar to that observed in human scleroderma. Heterozygous mice develop skin fibrosis shortly after birth, providing a valuable model to investigate the sequence of events leading to fibrosis. EXPERIMENTAL DESIGN: We have studied by in situ RNA hybridization the expression of procollagen alpha 1(I), alpha 1(III), alpha 2(VI) and transforming growth factor-beta 1 (TGF-beta 1) genes in the skin of Tsk mutant and normal newborn to aged mice. Tsk and normal skin sections at each age were mounted on the same slide to ensure identical experimental conditions, allowing for comparative analyses. RESULTS: All genes are under temporospatial regulation and exhibit characteristic patterns of expression during postnatal skin growth and development. TGF-beta 1 mRNA is detected in fibroblasts only during the rapid postnatal growth of the skin in parallel with high collagen I, III, and VI gene expression. Collagen I and III gene-expressing fibroblasts are observed in excess in the Tsk fibrotic lesions. An abnormal pattern of collagen VI expression is only observed at later stages in the fibrotic process. Collagen VI shows a different expression pattern in both normal skin development and fibrosis, suggesting noncoordinate regulation with collagen I and III genes. CONCLUSIONS: The fibrotic process in Tsk mice results from the persistence of high collagen I and III expression by a subpopulation of fibroblasts. Collagen VI overexpression participates later in the fibrotic process. In contrast with human scleroderma and other skin fibrotic diseases, TGF-beta 1 mRNA is not detected in the areas of abnormal collagen expression and fibrosis of Tsk. Alternative pathways should be explored to understand the abnormal extracellular matrix deposition of Tsk fibroblasts.

Animals↗

Relationship between gamma-ray-induced G2/M delay and cellular radiosensitivity.

Seven human and rodent cell lines with markedly differing cellular radiosensitivities were examined by the anti-Br-dUrd antibody and flow cytometric method in order to measure the progression of S phase cells and their accumulation in the G2 phase of the cell cycle after gamma-irradiation. Exponentially growing cells were labelled with 10 microM BrdUrd for 2 h, gamma-irradiated, then washed and cultured at 37 degrees C. At 2-h intervals postirradiation, the cells were harvested and fixed for flow cytometric analysis. Two parameter distributions of BrdUrd content and DNA content were analysed. The time intervals for unirradiated labelled cells to progress from S to G2/M phase were about 450 min for the human squamous cell carcinoma cell lines SCC-12B.2 (D0 = 2.66 Gy), SQ-20B (D0 = 2.39 Gy) and SCC-61 (D0 = 1.07 Gy) as well as for wild-type CHO cells (D0 = 2.62 Gy). After irradiation with 2 Gy, SCC-12B.2, SQ-20B, CHO and human diploid AG1521 cells showed similar small G2/M delays (about 1 h), whereas, a G2/M delay of about 2.2 h occurred in radiosensitive SCC-61 cells and delays of 5.0-7.7 h were observed in two extremely radiosensitive mutant cell strains (human AT homozygote and CHO xrs-5 respectively). When the cells were irradiated with doses yielding similar levels of survival (about 10%), however, the duration of the G2/M delay was generally similar (2-4 h) in all seven cell lines indicating a parallel relationship between radiation-induced G2/M delay and cellular radiosensitivity. These results suggest that the delay time may be related to the level of unrepaired damage present in the cell as it approaches mitosis.

Animals↗

Intrapleural streptokinase in experimental empyema.

Intrapleural streptokinase has been used in multiloculated empyemas to enhance pleural space drainage, presumably by causing fibrinolysis of the interlocular septae. We evaluated the efficacy and safety of daily administration of 10,000 U intrapleural streptokinase or equal volumes of saline to enhance resolution of experimental empyema in the rabbit pleural space. Seventy-two hours after intrapleural turpentine, 10(8) colony-forming units each of Escherichia coli, Peptostreptococcus anaerobius, and Bacteroides fragilis were injected into the sterile pleural effusion of all animals. Immediately after bacterial inoculation, and daily for 3 days, animals received 10,000 U streptokinase or saline intrapleurally. Animals that achieved a pleural fluid pH < 7.30 and either glucose < 50 mg/dl or LDH > 500 IU/L were included for data analysis. At Day 4 after bacterial inoculation, the streptokinase-treated empyemic rabbits had more pleural fluid (18.8 +/- 5.1 ml) (mean +/- SEM) than did saline-treated control animals (4.8 +/- 1.7 ml) (p = 0.015), fewer interpleural adhesions (8.2 +/- 2.7) than did saline-treated control animals (25.1 +/- 3.6) (p = 0.002), and comparable amounts of visceral and parietal pleural plaque than did saline-treated control animals (p = NS). No evidence of systemic fibrinolysis was observed at 1 h after intrapleural streptokinase administration. We conclude that intrapleural streptokinase decreases interpleural adhesion numbers but fails to reduce the amount of pleural plaque observed in experimental empyema in rabbits. The increases in pleural fluid volume observed after streptokinase administration may be due to mechanisms other than fibrinolytic activity.

Animals↗

Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy.

We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted.

Adult↗

Ketotifen prevents skin fibrosis in the tight skin mouse.

Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma.

Animals↗