Biomedical subjects
Publications and source records attributed to G R Smith.
Five virulent strains of Fusobacterium necrophorum resembled a single strain examined earlier by possessing little or no immunogenicity: severe subcutaneous infections cured with metronidazole failed to increase the resistance of mice to subcutaneous challenge 22 days after the cessation of treatment.
In order to understand psychiatric factors that complicate the medical management of somatizing patients, 94 subjects with known somatization disorder (SD) were evaluated for 13 personality disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. Referred from multiple primary care settings, the patient sample was predominantly female (85%), married (67%), high school graduates (64%), and had a mean age of 43. Structured interviews documented that 23.4% of SD patients had one personality disorder, and 37.2% had two or more disorders. The four most frequently identified personality disorders were avoidance 26.7%, paranoia 21.3%, self-defeating 19.1%, and obsessive-compulsive 17.1%. Interestingly histrionic personality disorder was identified in only 12.8% of the sample and antisocial personality disorder in 7.4%. In making the diagnosis of SD, health care providers need to avoid the common clinical impression that histrionic behavior often accompanies the disorder. Further research with SD patients is needed to examine the relationship of co-occurring personality disorders to symptom recurrence, health care utilization, and readiness for psychiatric referral.
This article reviews the relationship between depressive disorders and somatoform disorders, somatization, and pain. These disorders and symptoms are clinically interrelated, yet the nature of the interrelation is not well understood. This review of the literature from 1975 through mid-year 1990 addresses the epidemiology and treatment of these conditions and/or symptoms when they occur together. When robust criteria are used to determine which publications are included, only 14 are available that address depressive disorders, somatoform disorders, and somatization. Similarly, there are only 13 that address depressive disorders and pain. Taken together, these studies indicate that 1) in somatization disorder patients, there is a high prevalence of depression; 2) in patients with major depression, there are substantial levels of hypochondriacal and somatizing symptoms; 3) that depression in the face of coexisting somatization disorder can be successfully treated; 4) in chronic pain patients, there is a high prevalence of depressive disorders; 5) in patients with major depression, pain is a frequent complaint; 6) and finally, that pain improves with the treatment of depression. What is most striking from this review, however, is the very limited number of studies that address these important problems. This lack of research-based data calls for new aggressive research efforts in this area.
A 450-bp region from one species of the segmented dsRNA genome of Fiji disease virus (FDV) was amplified from total nucleic acid extracts of diseased plants by reverse transcription with MMLV, followed by amplification with Taq DNA polymerase (RT-PCR). Other FDV-specific regions (c 150 bp and c 270 bp) were also amplified from the dsRNA template. FDV cDNA was only synthesised when the viral dsRNA template was boiled and quenched with FDV-specific or random hexamer primers. The reverse transcriptase/DNA polymerase enzyme rTth appeared to yield only the 150 bp fragment from the dsRNA template under the conditions used. The level of sensitivity of RT-PCR for purified FDV dsRNA was 100 ag, approximately 10(4)-fold more sensitive than detection with biotinylated DNA probe.
Considerable data have demonstrated that psychological states can influence the immune system in animals. Whether human immune function can be intentionally modulated by the central nervous system is unknown. This article presents data from two studies that sought to demonstrate intentional modulation of the immune system by psychological interventions. It also discusses the methodological complexities involved with this type of research in humans.
We have analyzed 43 recessive mutations reducing meiotic intragenic recombination in Schizosaccharomyces pombe. These mutations were isolated by a screen for reduced plasmid-by-chromosome recombination at the ade6 locus. Sixteen of the mutations define 10 new complementation groups, bringing to 17 the number of genes identified to be involved in meiotic recombination. The mutations were grouped into three discrete classes depending on the severity of the recombination deficiency in crosses involving the ade6-M26 recombination hotspot. Class I mutations caused at least a 1000-fold reduction in M26-stimulated intragenic recombination at the ade6 locus. Class II mutations reduced M26-stimulated recombination approximately 100-fold. Class III mutations caused a 3-10-fold reduction in either M26-stimulated or non-hotspot recombination. We obtained multiple alleles of class I and class II mutations, suggesting that we may be nearing saturation for mutations of this type. As a first step toward mapping, we used mitotic segregation to assign fourteen of the rec genes to chromosomes. Mutations in the six rec genes tested also caused a decrease in intragenic recombination at the ura4 locus; five of these mutations also reduced intergenic recombination between the pro2 and arg3 genes. These results indicate that these multiple rec gene products are required for high level meiotic recombination throughout the S. pombe genome.
The Schizosaccharomyces pombe rec7 and rec8 genes, which are required for meiotic intragenic recombination but not for mitotic recombination, have been cloned and their DNA sequences determined. Genetic and physical analyses demonstrated that the cloned fragments contained the rec genes rather than rec mutation suppressors. A 1.6-kb DNA fragment contained a functional rec7 gene, and a 2.1-kb fragment contained a functional rec8 gene. The nucleotide sequences of these fragments revealed open reading frames predicting 249 amino acids for the rec7 gene product and 393 amino acids for the rec8 gene product. Northern hybridization analysis showed that both rec gene mRNAs were detectable only at 2-3 hr after induction of meiosis. The absence of these mRNAs in mitosis and their disappearance at 4 hr and later in meiosis suggest that the rec7 and rec8 gene products may be involved primarily in the early steps of meiotic recombination in S. pombe.
The major pathway of homologous recombination in Escherichia coli, the RecBCD pathway, is stimulated by Chi sites. To determine whether Chi enhances an early or late step in recombination, we measured formation of heteroduplex DNA (hDNA) in extracts of lambda-infected E. coli. Chi elevated hDNA levels in these extracts, supporting a role for Chi early (before hDNA formation) in recombination. RecA protein and RecBCD enzyme were both necessary for detection of hDNA, indicating that they, too, act early. Analysis of a panel of recBCD mutants indicated that Chi-nicking activity was needed for Chi's stimulation of hDNA formation. These results support a previously proposed model of recombination. Further results suggested that RecBCD enzyme has an additional role late in recombination.
To conduct effectiveness research in mental health, many nontrivial problems need to be addressed. A multidisciplinary expert panel designed an outcomes module for major depression and dysthymia to measure disease-specific outcomes, treatments routinely provided, and patient characteristics that influence treatment or its outcomes. The outcomes module was pilot-tested to evaluate its ability to identify a diagnostically homogeneous group of patients, to establish its reliability and validity, and to assess the feasibility of administering the module in a mental health setting. In a cohort of 40 patients, the module identified all 31 patients who had a research diagnosis of major depression or dysthymia (100% sensitivity), and 2 of 9 patients who did not have this diagnosis (77.8% specificity). The outcomes module measured key constructs accurately enough to discriminate between groups of depressed patients expected to differ, indicating positive construct validity. High rates of instrument completion supported the feasibility of using the module in specialty settings. Extensive efforts locating patients for follow-up will be needed to draw valid conclusions about treatment effectiveness.
We estimated the prevalence of psychiatric disability and disorders (depression, mania, schizophrenia, alcohol disorder, drug disorder, antisocial personality, and somatization) in the parents, siblings, and children of three groups of index cases: primary care patients with somatization disorder (n = 70), primary care patients who approached, but did not reach, DSM-III-R criteria for somatization disorder (n = 29), and randomly-selected community residents with no psychiatric disorder (n = 1633). Nearly all psychiatric disorders were more common in relatives of both patient samples than in relatives of community residents, and the patient samples rarely differed from each other. In the patient samples, the 22.9% rate of patients with multiple unexplained medical problems is substantially higher than previous investigations of somatization would predict. The most common disorders in patients' relatives were depression and alcohol disorder. There was little difference in the rates of depression in relatives of somatization patients who were or were not themselves depressed. A similar pattern occurred for alcohol disorder. There was a high risk for antisocial personality disorder in parents of patients meeting DSM-III-R criteria for somatization disorder, but this increase was not found for other relatives.
In this study, the cost and health outcomes of a psychiatric consultation letter to primary care physicians caring for a sample of patients diagnosed with somatization disorder, a psychiatric condition associated with multiple, unexplained medical complaints, was assessed. To accommodate the small sample size of 73 patients, outcome effects were calculated using panel analysis. Study patients were randomized to a consultation or noconsultation group, and were repeatedly assessed at equal time intervals. Data were analyzed using parsimonious regression models derived from economic theory. During the 1-year follow-up period, a psychiatric consultation letter was associated with a 12% reduction in health care costs ($455 per patient within first year), with no evidence of deterioration in physical, mental, or general health. Less powerful t-test comparisons between treated and control groups lead to different conclusions. Reasons for these differences are discussed.
We examined how return to work predicted subsequent change in emotional distress in 143 patients who had been employed at the time of initial myocardial infarction. Ninety patients (63%) returned to work by 4 months and remained employed at 12 months. There were no differences in mental health at baseline between those who returned to work and those who did not, but emotional distress decreased significantly between 4 and 12 months only in the group who returned to work. Emotional distress declined after resuming work even when employees returned to jobs with which they reported dissatisfaction at the time of the myocardial infarction. The relationship between return to work and decreasing emotional distress remained after controlling for initial physical and psychological adjustment as well as sociodemographic and social support characteristics. The improvements in mental health associated with return to work should reassure clinicians who emphasize the emotional as well as economic value of work after an initial myocardial infarction.
Intrauterine swabs were obtained from cows after calving on two commercial dairy herds with contrasting hygienic environments and incidence of leucorrhea, and cultured aerobically and anaerobically. Of 26 cows with a normal calving and puerperium, eight of 14 (57 per cent) were sterile on farm B where hygiene was poor, compared with five of 12 (42 per cent) on farm A where hygiene was better. Two cows on farm B retained their placentas and subsequently developed metritis/endometritis. Actinomyces pyogenes was the commonest bacterial isolate and Fusobacterium nucleatum, Proteus mirabilis and Bacteroides melaninogenicus were also frequently observed. Similar isolates were obtained from cows on farm B with parturient or puerperal disorders. The contrasting hygienic environments had no influence on either the quantitative or qualitative uterine bacterial flora. Thus, the difference in the incidence of endometritis must have been due to factors other than hygiene.
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Somatization disorder is thought to be rare or nonexistent in men. We examined this hypothesis by assessing gender differences in DSM-III-R diagnostic status, demographic and clinical characteristics, functional limitations, self-reported health status, and psychiatric comorbidity in 30 men and 117 women who were referred for multiple unexplained somatic complaints. Twelve men and 68 women met DSM-III-R criteria for somatization disorder. Among those meeting criteria, there were few differences on any of the dimensions that were assessed. Different referral sources for women and men suggested differences in physicians' perceptions of somatic symptoms in men and women. We concluded that somatization disorder exists in men, and that women and men with somatization disorder show similar clinical characteristics.
This study examined the relationship of function-specific mental health measures, anxiety and depression subscales of the Mental Health Index (MHI), to psychiatric diagnoses of generalized anxiety disorder and major depression, as assessed by the Diagnostic Interview Schedule (DIS). Focusing on the clinical relevance of the MHI scales, we evaluated their performance in screening for DIS-diagnosable disorders in a sample of primary care patients with multiple unexplained somatic symptoms. Receiver Operating Characteristic curves and examples of sensitivity, specificity, and predictive value for different cutoff scores on the MHI are presented. When sensitivity is set at approximately 90%, positive predictive value exceeds 50%. Because the base rates of disorder in this sample are high, however, the screening measure has little independent usefulness. Similarly, cutoff scores yielding negative predictive value of approximately 90% fail to detect most of the true-negative cases. Future research should examine the use of these scales in other high-risk populations.
It had already been shown with a single virulent strain (A42) of Fusobacterium necrophorum that suspension of the fusobacteria in sub-lethal doses of broth cultures of other bacteria reduced the minimum infective dose (greater than 10(6) organisms) for mice by subcutaneous inoculation, sometimes to less than 10 organisms. The present study extended the known range of bacteria with strong infectivity-enhancing properties to include Bacillus cereus, Klebsiella oxytoca and Staphylococcus aureus; and those with weaker effect to include Bacillus subtilis, 'Bacteroides melaninogenicus', Clostridium sporogenes, Pasteurella haemolytica, and Proteus mirabilis. The study also showed that five further virulent strains of F. necrophorum closely resembled A42 in respect of striking susceptibility to infectivity enhancement by Escherichia coli. Actinomyces (Corynebacterium) pyogenes and S. aureus. One further strain (A6) of F. necrophorum resembled A42 in respect of strong infectivity enhancement by A. pyogenes, S. aureus, B. cereus and K. oxytoca but differed from it and the other five strains in being only slightly affected by E. coli. This work was a necessary prelude to the development of a method, based on infectivity enhancement, for the detection and isolation of F. necrophorum present in small numbers in heavily contaminated material such as faeces.
The isolation of Fusobacterium necrophorum present in small numbers in heavily contaminated material such as faeces or soil is hampered by the lack of an efficient selective medium and by the high minimum infective dose of the organism. A sensitive method for the detection and isolation of faecal strains of F. necrophorum type A was based on the subcutaneous injection of faeces, suspended (5% w/v) in broth culture of Actinomyces (Corynebacterium) pyogenes or Staphylococcus aureus to increase fusobacterial infectivity, into mice pretreated with clostridial antitoxins. When necrobacillosis developed F. necrophorum was identified microscopically in tissue from the advancing edge of the lesion and isolated on a partly selective medium. The enhancement of fusobacterial infectivity produced by A. pyogenes and by S. aureus was high, but the latter was slightly the more efficient, enabling as few as 80 F. necrophorum organisms/g of faeces to be detected. Use of the method showed that 3 of 16 wallabies had F. necrophorum in their faeces at the time of examination. Numerous epidemiological applications are suggested.