Two-year evaluation of the logic model for developing a psycho-oncology service

OBJECTIVE: The objective of this study was to test whether reorganizing a psycho-oncology service in a planned and focused manner would maximize the achievement of coherent developmental goals. METHODS: The logic model, a strategic program development tool, was used in the context of a public psychiatry fellowship to analyze and plan the organizational objectives of a psycho-oncology service. To assess the efficacy of the logic model, a two-year prospective evaluation of the model's outcome measures was performed. RESULTS: The psycho-oncology service was systematically reorganized through use of the logic model. Qualitative and quantitative data identified the degree of goal achievement. Most of the short- and medium-term clinical, educational, and research goals, as measured by outcome measures, had been realized at the two-year point. CONCLUSIONS: The logic model facilitated the effective reorganization of a psycho-oncology program by analyzing the existing service, developing pertinent goals, and then measuring goal attainment. These findings will be useful to psychiatric services interested in rational program development and service delivery, especially in small and medium hospitals with limited resources.     

Novelty seeking and harm avoidance in Parkinson's disease: effects of asymmetric dopamine deficiency

OBJECTIVES: Although changes in novelty seeking and harm avoidance have been reported among patients with Parkinson's disease (PD), the findings regarding the neurochemical correlates of such changes are inconsistent. This study was designed to examine the hypothesis that different patterns of motor and neurochemical asymmetry in PD may have contributed to the conflicting results. METHODS: Forty PD patients (divided into two groups according to initial asymmetry in dopamine deficit: left hemisphere, n = 22; right hemisphere, n = 18) and 17 age matched healthy controls completed the Tridimensional Personality Questionnaire (Cloninger, 1987). RESULTS: Only patients with greater dopamine loss in the left hemisphere showed reduced novelty seeking, whereas only patients with reduced dopamine in the right hemisphere reported higher harm avoidance than matched healthy controls. Novelty seeking was not associated with disease duration, current motor symptoms, or medication, whereas harm avoidance was significantly correlated only with the severity of bradykinesia and depression. CONCLUSIONS: Approach and avoidance reflect different patterns of dopaminergic asymmetry. Whereas reduced novelty seeking reflects deficit in the mesolimbic branch of ascending dopamine transmission in the left hemisphere, increased harm avoidance is associated with greater dopamine loss in the right striatum.     

The contribution of immune regulatory and thyroid specific genes to the etiology of Graves' and Hashimoto's diseases

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) are believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely these loci interact and their interactions may influence disease phenotype and severity.     

A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome

OBJECTIVE: To examine whether the insulin receptor (INSR) gene contributes to genetic susceptibility to the polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Academic endocrinology clinic. PATIENT(S): Ninety-nine women with PCOS as defined by the National Institutes of Health consensus and polycystic ovaries on ultrasonography, and 136 healthy controls. MAIN OUTCOME MEASURE: Frequency of genotypes of a single nucleotide polymorphism of the INSR gene in patients and controls. RESULT(S): After stratification of participants by body mass index, the frequency of the uncommon T allele of the INSR single nucleotide polymorphism was significantly increased in lean patients with PCOS (body mass index < or =27 kg/m2) compared with lean controls (relative risk, 2.1). CONCLUSION(S): The INSR gene is a susceptibility gene for PCOS among lean patients with PCOS. It remains to be determined whether the exon 17 C/T single nucleotide polymorphism is the susceptibility single nucleotide polymorphism for PCOS or whether it is in linkage disequilibrium with another INSR gene polymorphism.     

T2-weighted image hyperintensities in major depression: focus on the basal ganglia

A major focus of attention in structural brain-imaging research in major depression is the increased prevalence of T2-weighted image 'hyperintensities' (T2-WIH). Our aims in this study were to characterize the distribution and magnetic resonance imaging (MRI) presentation of brain hyperintensities in major depression patients compared to healthy control subjects and to explore the association between the presence of T2-WIH and measures of clinical and cognitive state. Thirty-seven patients suffering from major depression and 27 age- and sex-matched healthy controls underwent brain MRI and were evaluated by the Hamilton Rating Scale for Depression, the Mini Mental State Examination and the Haschinsky Ischaemia Index. T2-WIH (at least one) were found in 26 out of 37 major depression patients and 7 out of 27 controls (p=0.0001). The number of brain T2-WIH was significantly and positively correlated with age in depressed (p=0.001) but not in healthy subjects. Mean volume of T2-WIH was significantly greater (p=0.004) in depressed subjects. In the control group T2-WIH were exclusively located in the supratentorial hemispheral white matter while in the depressed group T2-WIH were also found in basal ganglia, temporal lobe, cerebellum and brainstem. More (52 vs. 20%; p=0.018) T2-WIH were demonstrable on T1 in depressed subjects. Depressed patients with T2-WIH in basal ganglia were clearly the most severely depressed and cognitively impaired subjects, and may constitute a clinically distinct subgroup within major depression.     

Enhanced erythrocyte adhesiveness/aggregation in obesity corresponds to low-grade inflammation

OBJECTIVE: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. RESEARCH METHODS AND PROCEDURES: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 +/- 7.7 kg/m(2)] and 35 nonobese (BMI = 24 +/- 2.7 kg/m(2)) individuals. Pearson correlations and Student's t test were performed. RESULTS: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high-sensitive C-reactive protein (r = 0.55, p < 10(-4)), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10(-4)). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10(-4)), high-sensitive C-reactive protein (r = 0.56, p < 10(-4)), fibrinogen (r = 0.54, p < 10(-4)), and white blood cell count (r = 0.32, p = 0.01). DISCUSSION: Our results suggest that obesity-related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.     

Thrombogenesis in sickle cell disease

Thirty-three subjects with sickle cell disease (SCD), 11 during episodes of pain and 22 during periods without pain, were evaluated for in vivo thrombogenic activities as compared with 10 normal black control subjects. Measurements were performed for (1) platelet surface activation, assessing flow cytometric expression of activated integrin alpha(IIb)beta(3) receptor (GPIIb/IIIa, CD41a) and P-selectin (CD62p); (2) platelet and erythrocyte surface procoagulant activities, measuring flow cytometric binding of activated factor (FVa) and annexin V; (3) plasma levels of platelet-specific secreted proteins platelet factor 4 (PF4) and beta-thromboglobulin (betaTG); (4) plasma markers of thrombin generation, prothrombin activation fragment (F(1.2)), and thrombin: antithrombin complex (TAT); and (5) plasma markers of fibrinolysis, D -dimer, and plasmin:antiplasmin complex (PAP). As compared with control subjects, asymptomatic subjects with SCD demonstrated significantly increased platelet activation (P <.01 for P-selectin and annexin V binding), elevated plasma levels of PF4 and betaTG (P <.01 and P <.03, respectively), and increased plasma concentrations of F(1.2), TAT, PAP, and D -dimer (P <.05 in all cases). During episodes of SCD pain, platelet activation was increased as compared with periods without pain (P <.01 for expression of activated integrin alpha(IIb)beta(3) receptor and P-selectin and binding of FVa and annexin V), erythrocytes expressed procoagulant activities (P <.01 for FVa and annexin V binding), and platelet microparticles appeared in the circulation (3% to 30%; P <.001). SCD pain episodes were associated with elevated plasma levels of F(1.2), TAT, PAP, and D -dimer (P <.05 as compared with asymptomatic intervals). The frequency of pain episodes correlated with enhanced platelet procoagulant activity (r = 0.61, P <.05) and elevated plasma fibrinolytic activity (r = 0.74, P <.01) measured during periods without pain. Plasma fibrinolytic activity was inversely correlated with time to the next pain episode (r = -0.50, P <.05). Thus, asymptomatic subjects with SCD exhibit ongoing platelet activation, thrombin generation, and fibrinolysis that increases during episodes of pain. These changes are predictive of frequency of pain and interval to next pain episode, thereby implicating thrombogenic activity in the development of SCD pain episodes.     

Prognostic factors in non-metastatic limb osteosarcoma: A 20-year experience of one center.

The purpose of this study was to evaluate the prognostic significance of variables in osteosarcoma. We performed a retrospective analysis of 35 patients with non-metastatic limb osteosarcoma that were treated between 1973 and 1994. The following variables were evaluated: age, sex, ethnic group, tumor histology and primary site, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels at diagnosis, treatment regimen, and the histologic response to treatment. Three variables showed significant correlation with prognosis: i) histologic response to preoperative treatment. Disease-free survival (DFS) was 89% in patients with grade III-IV histologic response after a median follow-up (MFU) of 64 months, 67% in patients with grade II after an MFU of 64 months, the patients with grade I response died within 15 months (p<0.0001); ii) treatment regimen. DFS was 83% after an MFU of 42 months, 62% after an MFU of 82 months, and 30% after an MFU of 177 months in patients treated by the 90's, 80's, and 70's protocols, respectively (p<0.05); iii) corrected ALP (cALP) levels at diagnosis. DFS was 78% after an MFU of 88 months in patients with cALP levels <200, and 32% after an MFU of 56 months in patients with cALP levels >200 (p=0.01). Low ALP levels, good histologic response to preoperative chemotherapy, and the new therapeutic regimen correlated with good prognosis in patients with osteosarcoma.     

Cytokines in experimental autoimmune vasculitis: evidence for a Th2 type response.

OBJECTIVE: To investigate the pathogenic role of cytokines in the development of experimental autoimmune vasculitis. METHODS: BALB/c mice were immunized with human IgG-ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse IgG-ANCA and other autoantibodies were determined. The mice lungs and kidneys were examined for the development of vasculitis. Levels of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, interferon gamma (IFN gamma) and TNF alpha were determined by ELISA two weeks after immunization of the mice. RESULTS: Mice immunized with human IgG-ANCA developed anti-human IgG-ANCA (= Ab2) and anti-anti-human IgG-ANCA (mouse IgG-ANCA = Ab3), while the controls did not develop these antibodies. The mice that were immunized with human IgG-ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. Levels of IL-4, IL-6 and TNF alpha but not IL-1 beta, IL-2 and IFN gamma were significantly elevated in the mice 2 weeks after immunization with IgG-ANCA. CONCLUSION: Our results suggest a pathogenic role for IL-4, IL-6 and TNF alpha in the initiation phase of autoimmune vasculitis. This suggests that a Th2 type immune response is responsible for the initiation of experimental autoimmune lung vasculitis, similar to Wegener's granulomatosis in humans.