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Biomedical subjects

J C Simpson

Publications and source records attributed to J C Simpson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Negative, positive, and disorganized symptom dimensions in schizophrenia, major depression, and bipolar disorder.

We compared the factor structure of positive and negative symptoms in schizophrenia (N = 214), major depression (N = 97), and bipolar disorder (N = 58) to determine whether schizophrenia factors would generalize to mood disorders. A study of schizophrenia and mood disorders identified patients whose symptoms were evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. We conducted principal component analyses with orthogonal rotation on the global ratings. The factor structure replicated earlier findings of three factors (negative, positive, and disorganization) in groups with schizophrenia, combined mood disorders, and psychotic symptoms, regardless of diagnosis. An additional negative symptom factor was found in the major depression group. The bipolar group did not have a disorganization factor. Similar symptom factors in schizophrenia and mood disorders suggest a continuity in the major affective and psychotic disorders that appears to reflect the underlying dimension of a psychotic process.

Adult↗
PubMed1998

Prevalence and predictors of work related respiratory symptoms in workers exposed to organic dusts.

OBJECTIVES: The aims of this study were to document the prevalence of work related upper and lower respiratory tract symptoms in workers exposed to organic dusts and to identify variables predictive of their occurrence. METHODS: A cross sectional survey with an administered questionnaire (a previously validated adaptation of the Medical Research Council (MRC) respiratory questionnaire) was performed. Symptoms were classified as work related by their periodicity. Demographic data, smoking habits, and occupational histories were recorded. Personal exposures to dust and endotoxin were measured and individual subjects ascribed an exposure value specific to occupation, site and industry. Cox's regression techniques were used to identify variables predictive of work related upper and lower respiratory tract symptoms. Information was stored using Dbase 3 and analysed with SPSS. RESULTS: 1032 Workers (93% of the target population) were studied in nine different industries. The highest prevalences of work related lower respiratory tract symptoms (38.1%), upper respiratory tract symptoms (45.2%), and chronic bronchitis (15.5%) were found among poultry handlers. White workers were significantly more likely to complain of upper and lower respiratory tract symptoms. An individual in the swine confinement industry had a symptom complex compatible with byssinosis. Increasing current personal exposures to dust or endotoxin were found to be predictive of upper and lower respiratory tract symptoms, chronic bronchitis, and byssinosis. In a univariate analysis a relation between current exposures and the organic dust toxic syndrome was found. Present smoking and previously documented respiratory tract illness were significantly predictive of work related lower respiratory tract symptoms. Women were more likely to report work related upper respiratory tract symptoms. CONCLUSIONS: People exposed to organic dusts may have a high prevalence of work related respiratory tract symptoms which are related to dust exposures and smoking habits. Action should be taken to reduce exposures to dust and endotoxin and stopping smoking should be promoted among workers exposed to organic dusts to reduce morbidity.

Adult↗
PubMed1998

Do radiographic features of acute infection influence management of lower respiratory tract infections in the community?

Community-acquired lower respiratory tract infection (LRTI) is a common clinical problem, and a chest radiograph is the most common investigation. This study investigated why general practitioners (GPs) request radiographs and whether radiographic features of LRTI affect management. The 12 month study included GP-requested chest radiographs performed at the Manchester Royal Infirmary. The GPs of patients with radiographic evidence of LRTI were sent a questionnaire. Radiographs (n=2,538) were performed in patients aged >15 yrs. One hundred and eleven (4.4%) chest radiographs showed evidence of LRTI, and 97 (87%) were included in the analysis. Fifty-six (62%) had their radiograph requested at the second or third visit. Forty-five (58%) radiographs were performed to confirm infection. In 47 (48%) of cases the GP felt the radiograph had affected treatment. An effect on treatment was significantly more common in patients not receiving antibiotics prior to the radiograph. Twenty-nine (32%) of GPs felt a normal radiograph would have affected management, most often with respect to antibiotic prescriptions (17 (58%)). Where the radiologist's report suggested a repeat radiograph or hospital referral, this was significantly more likely to have occurred. The commonest reason for a radiograph in patients with suspected lower respiratory tract infection is to confirm the infection. In the opinion of the general practitioner the results of the radiograph do affect patient treatment. The wording of the radiologists report is associated with patient management.

Acute Disease↗
PubMed1997

Chronic bronchitis in textile workers.

BACKGROUND: Exposure to cotton is known to produce a specific occupational disease known as byssinosis. A large population of textile workers was investigated to determine whether such exposure was also associated with chronic bronchitis once other possible aetiological factors had been accounted for. METHODS: A total of 2991 workers were investigated for the presence of symptoms compatible with chronic bronchitis. An MRC adapted respiratory questionnaire and MRC definition of chronic bronchitis were used for diagnostic labelling. Current and lifetime exposure to dust was estimated by personal and work area sampling, and the use of records of retrospective dust levels previously measured over the preceding 10 years. Airborne endotoxin exposure was measured using a quantitative turbidometric assay. Lung function tests were performed to measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A control group of workers exposed to man-made fibre textiles was identified. The comparative prevalence of chronic bronchitis in the two populations was assessed, allowing for sex, age, smoking habit, and ethnic origin. Two case referent studies were also performed; cases of chronic bronchitis were separately matched with controls from the cotton and control populations to determine the effect of the symptomatic state on lung function. RESULTS: After controlling for smoking (pack years), workers in a cotton environment were significantly more likely to suffer from chronic bronchitis and this was most marked in workers over 45 years of age (odds ratio 2.51 (CI 1.3 to 4.9); p < 0.01). Regression analysis of all possible influencing parameters showed that cumulative exposure to cotton dust was significantly associated with chronic bronchitis after the effects of age, sex, smoking, and ethnic group were accounted for (p < 0.0005). In the intra-cotton population case control study a diagnosis of chronic bronchitis was associated with a small decrement in lung function compared with controls: percentage predicted FEV1 in cases 81.4% (95% CI 78.3 to 84.6), controls 86.7% (84.9 to 88.5); FVC in cases 89.9% (95% CI 87.0 to 92.9), controls 94.6% (92.8 to 96.4). After controlling for cumulative past exposure and pack years of smoking the effect of the diagnostic state remained significant for both FEV1 (p < 0.01) and FVC (p < 0.05). CONCLUSIONS: Chronic bronchitis is more prevalent in cotton workers than in those working with man-made fibre and exposure is additive to the effect of smoking. The diagnosis of chronic bronchitis is associated with a small but significant decrement in lung function.

Adult↗
PubMed1997

Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients.

OBJECTIVE: The factor structures of individual positive and negative symptoms as well as global ratings were examined in a diagnostically heterogeneous group of subjects. METHOD: Subjects were identified through a clinical and family study of patients with major psychoses at a VA medical center and evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. For the examination of global-level factor structures (N = 630), both principal-component analysis and factor analysis with orthogonal rotation were used. Factor analysis was used for the examination of item-level factor structures as well (N = 549). RESULTS: The principal-component analysis of global ratings revealed three factors: negative symptoms, positive symptoms, and disorganization. The factor analysis of global ratings revealed a negative symptom factor and a positive symptom factor. The item-level factor analysis revealed two negative symptom factors (diminished expression and disordered relating), two positive symptom factors (bizarre delusions and auditory hallucinations), and a disorganization factor. CONCLUSIONS: The generation of additional meaningful factors at the item level suggests that important information about symptoms is lost when only global ratings are viewed. Future work should explore clinical and pathological correlates of the more differentiated item-level symptom dimensions.

Adult↗
PubMed1997

Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996.

OBJECTIVE: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. DESIGN AND SETTING: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Health Department. Controls were healthy infants. Medical history information on infants and mothers were collected, along with DNA samples. PATIENTS, PARTICIPANTS: Among 286 cases contacted (72% ascertainment), there were 192 nonsyndromic isolated oral clefts (106 M; 86 F) available for this case-control study. MAIN OUTCOME MEASURES: The largest group of 149 Caucasian nonsyndromic cases and 86 controls was used to test for association with maternal smoking and genotype at the Taq1 polymorphism in TGFA. RESULTS: While this modest sample had limited statistical power to detect gene-environment interaction, there was a significant marginal increase in risk of having an oral cleft if the mother smoked (odds ratio = 1.75, 95% CI = 1.01 to 3.02). We could not demonstrate statistical interaction between maternal smoking and TGFA genotype in this study, however, and the observed increase in the C2 allele among cases was not statistically significant. CONCLUSIONS: We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this effect was greatest among infants with a bilateral cleft and no close family history of clefts.

Alleles↗
PubMed1996

Free ricin A chain reaches an early compartment of the secretory pathway before it enters the cytosol.

During the intoxication of mammalian cells by ricin, the catalytically active A chain must cross the membrane of an intracellular compartment in order to reach its ribosomal substrates in the cytosol. The actual site of ricin A chain translocation is unclear, and conflicting views hold that it enters the cytosol from endosomes or from an early compartment of the secretory pathway, possibly the lumen of the endoplasmic reticulum. Here we show that treating cells with brefeldin A, or transiently overexpressing mutant GTPases known to inhibit biochemical complexes mediating anterograde and retrograde transport between the endoplasmic reticulum and the Golgi complex, protected cells from intoxication by free ricin A chain. These data indicate that ricin A chain, either free or as part of intact ricin, reaches an early compartment of the secretory pathway before translocation into the cytosol occurs.

Amino Acid Sequence↗
PubMed1996

Mortality among patients with schizophrenia.

Results from a 40-year followup study of psychotic patients are presented to illustrate some of the major findings and unanswered questions about excess mortality in schizophrenia and to suggest analytical approaches that take full account of the potential effects of sample heterogeneity. In this study, hospital-diagnosed schizophrenia patients were at increased mortality risk whether or not they met research criteria for schizophrenia. In addition, mortality outcomes of several major diagnostic groups were similar despite substantial clinical and demographic differences between the groups at baseline. These results suggest that both diagnosis-specific and nondiagnostic factors are needed to account for excess mortality in patients with major psychiatric disorders. The issue of heterogeneity is also crucial for the clinical purposes of predicting and ultimately reducing the mortality risk of psychiatric patients, for example, in delineating profiles of high-risk patients who are not necessarily typical of other patients with the same diagnosis.

Adult↗
PubMed1996

Reconstruction of radionuclide releases from the Hanford Site, 1944-1972.

Historic releases of key radionuclides were estimated as a first step in determining the radiation doses that resulted from Hanford Site operations. The Hanford Site was built in southcentral Washington State during World War II to provide plutonium for the U.S. nuclear weapons program. As part of the Hanford Environmental Dose Reconstruction (HEDR) Project, releases to the Columbia River of 24Na, 32P, 46Sc, 51Cr, 56Mn, 65Zn, 72Ga, 76As, 90Y, 131I, 239Np, and nonvolatile gross beta activity from operation of eight Hanford single-pass production reactors were estimated. Releases of 90Sr, 103Ru, 106Ru, 131I, 144Ce, and 239Pu to the atmosphere from operation of chemical separation facilities were also estimated. These radionuclides and the atmospheric and Columbia River pathways were selected for study because scoping studies showed them to be the largest contributors to dose from Hanford operations. The highest doses resulted from releases to the atmosphere of 131I from chemical separations plants in the pre-1950 period. Prior to 1950, the technology for limiting iodine releases had not been developed. Hence, a very detailed reconstruction of the hourly 131I release history was achieved for 1944-1949 using Monte Carlo methods. Atmospheric releases of the other radionuclides were estimated on a monthly basis for 1944-1972 using deterministic calculations. Monthly releases to the Columbia River for 1944-1971 were based on Monte Carlo methods.

Air Pollutants, Radioactive↗
PubMed1995

Point mutations in the hydrophobic C-terminal region of ricin A chain indicate that Pro250 plays a key role in membrane translocation.

A series of mutations have been made in the carboxyl terminus of ricin A chain, centred on the hydrophobic region between amino acid residues Val245 and Val256. The mutant ricin A chains were expressed to a high level in an Escherichia coli system and the proteins purified to homogeneity. The enzymic activity of each of these A chain molecules was tested on rabbit reticulocyte ribosomes; in all cases, the activities were found to be comparable to wild-type recombinant ricin A chain. Following reassociation of these A chains to ricin B chain, Vero cells were challenged with these holotoxins and the cytotoxicities determined. Mutant ricin A chain with Ile247-->Ala was unable to reassociate and form holotoxin, indicating the importance of this residue in the interaction with ricin B chain. Mutant ricin A chain with Pro250-->Ala readily reassociated with ricin B chain, forming holotoxin with a 170-fold reduction in cytotoxicity to Vero cells. Other mutations in this region also produced A chain proteins which gave marked reductions in holotoxin cytotoxicity. We propose therefore that the C-terminal hydrophobic region of ricin A chain may be involved in membrane interactions prior to the translocation of this subunit into the cytosol, and that Pro250 plays a key role in one or both of these steps.

Amino Acid Sequence↗
PubMed1995

Ricin cytotoxicity is sensitive to recycling between the endoplasmic reticulum and the Golgi complex.

Cytotoxic proteins that kill mammalian cells by catalytically inhibiting protein synthesis must enter the cytosol in order to reach their substrates. With the exception of diphtheria toxin, which enters the cytosol from acidified endosomes, the intracellular site of translocation of other toxins including ricin, Escherichia coli Shiga-like toxin-1, and Pseudomonas exotoxin A is likely to involve early compartments of the secretory pathway. We have used a molecular approach to identify the site and mechanism of toxin delivery to the cytosol by transiently expressing mutant GTPases that inhibit the assembly of biochemical complexes mediating anterograde and retrograde transport in the exocytic and endocytic pathways. The results provide evidence to suggest that receptors actively recycling between the endoplasmic reticulum and terminal Golgi compartments are essential for toxin translocation to the cytosol from the endoplasmic reticulum. The rapid kinetics of intoxication demonstrate a substantial level of bidirectional membrane flow and sorting through the early secretory pathway.

Amino Acid Sequence↗
PubMed1995

Catalytic and cytotoxic activities of recombinant ricin A chain mutants with charged residues added at the carboxyl terminus.

Ricin A chain (RTA) mutants which had been modified by the addition of three lysine residues, three lysines and an alanine, or six histidine residues at the carboxyl terminus were expressed in Escherichia coli. The recombinant proteins were purified to homogeneity by ion-exchange chromatography on CM-Sepharose CL-6B. The 28S ribosomal RNA N-glycosidase activities of the three RTA mutants were indistinguishable from each other and from the activity of wild-type recombinant RTA. The RTA mutants were not impaired, compared with wild-type RTA, in their ability to reassociate with ricin B chain to form ricin holotoxin. Holotoxins containing mutant RTAs were as readily dissociated into subunits under reducing conditions as native holotoxin, and the RTA mutants were indistinguishable from wild-type RTA in the extent of their interaction with biological membranes. Ricin holotoxins containing the RTA mutants were, however, less cytotoxic to Vero cells than ricin containing wild-type RTA. At equivalent concentrations, a time course assay showed that holotoxin containing the mutant RTAs took longer to kill target cells than that containing wild-type recombinant RTA, suggesting that the mutant forms of RTA are less efficiently processed or translocated across an intracellular membrane than is wild-type RTA.

Amino Acids↗
PubMed1992

Mathematical models of complex dose-response relationships: implications for experimental design in psychopharmacologic research.

We develop a mathematical model to account for the complex relationship between drug dose and clinical response in psychopharmacologic research. The model specifies relationships among drug dose, drug bioavailability, pharmacokinetic factors, course moderators, clinical response and the heterogeneity of the disorder, and allows for the derivation of results that have implications for experimental design in psychopharmacologic research. These results form the basis for computer simulations which indicate that random assignment to two fixed doses is more powerful and less sensitive to heterogeneity than assignment to clinically determined doses. Fixed dose designs, however, tend to overestimate the magnitude of drug bioavailability-clinical response relationships. Clinically determined dose designs are useful in some experimental situations; their effectiveness is enhanced by systematically reducing the clinically determined dose. Larger dose reductions improve the ability to detect bioavailability-clinical response relationships.

Antipsychotic Agents↗
PubMed1990

The role of gender in identifying subtypes of schizophrenia: a latent class analytic approach.

Past literature suggests that schizophrenic men and women may be at different risks for developing different subtypes of schizophrenia. This hypothesis was tested using data from the well-known retrospective cohort family studies, the Iowa 500 and the Iowa non-500. The sample consisted of 171 male and 161 female DSM-III schizophrenic patients and 713 of their first-degree relatives. First, bivariate tests for gender differences were conducted regarding family morbidity, age of onset, premorbid history, season of birth, and expression of deficit and affective symptoms. Restricted maximum likelihood latent class analysis was then used to test whether there was a subgroup of schizophrenic men who were more likely to have a low familial risk for schizophrenia or schizophrenia spectrum disorders, deficit symptoms, poor premorbid history, and birth in the winter months, suggesting possible early environmental insults, compared to schizophrenic women. Results showed that although men were more likely to meet these criteria, women also met them, thus suggesting gender differences in the prevalence of the subtype. Schizophrenic women were more likely to express a form of the illness characterized by dysphoria, persecutory delusions, and a higher family morbidity risk for schizophrenia than schizophrenic men. Results for spectrum disorders among relatives were equivocal with regard to gender.

Adult↗
PubMed1988

Outcome studies of schizoaffective disorders.

Outcome studies of schizoaffective disorder have taught us much about the long-term consequences of the syndrome, and they have provided some indication of the potential usefulness of maintaining "schizoaffective disorder" as a diagnostic category separate from schizophrenia and major affective disorder. In a review of outcome studies that compared schizoaffective patients to schizophrenic or affective patients, we found consistent results despite wide variations in diagnostic criteria, length of followup, and demographic characteristics. Global measures of outcome show that schizophrenic patients are more impaired than schizoaffective patients, who in turn are more impaired than affective patients. However, studies of specific outcome domains such as symptomatology, social functioning, and occupational functioning indicate that schizoaffective disorder is heterogeneous and that subtyping by polarity (e.g., schizoaffective-manic vs. schizoaffective-depressed) accounts for some of this variance. The consistency of these findings in the face of methodological variability suggests that it would be premature to classify schizoaffective patients with schizophrenia or affective disorder, but also that strict diagnostic criteria for schizoaffective disorder are at best preliminary and need to be thoroughly validated.

Bipolar Disorder↗
PubMed1986

Cardiac surgery in Jehovah's witnesses. A review of 36 cases.

Between January 1971 and January 1985, 31 Jehovah's witnesses underwent 24 bypass and 12 non-bypass cardiothoracic operations at the National Heart Hospital. Fifty-eight% of the group were under 16 years of age. There was one death in the non-bypass group unrelated to blood loss. Six deaths occurred in the bypass group. In one of these, blood loss contributed to the cause of death and in two patients, blood loss was directly related to the cause of death. The anaesthetic management of Jehovah's witnesses undergoing cardiac surgery is discussed.

Adolescent↗
PubMed1986

Ten-year follow-up of drug abusers with acute or chronic psychosis.

To assess whether long-term outcome of former drug abuse patients who had psychotic symptoms was related to duration of psychosis before hospitalization, the authors rated the psychiatric, occupational, and residential outcome of 101 former drug abuse patients based on interviews conducted ten years after their admission to a psychiatric hospital. At admission, 45 had had psychotic symptoms for six months or more; 26 had had psychotic symptoms for less than six months; and 30 had not been psychotic. Seventy-one former psychiatric patients who had had a psychotic illness but had not abused drugs were also interviewed and rated. Drug abusers with chronic psychosis had significantly worse psychiatric outcome than the other drug abusers and significantly worse occupational outcome than acutely psychotic drug abusers. The authors conclude that drug abusers with chronic psychotic symptoms are a distinct subgroup of drug abusers who suffer from major psychotic illness.

Acute Disease↗