An integrated medical and psychosocial treatment program for psychotic disorders: patient characteristics and outcome

OBJECTIVES: To provide an overview of a comprehensive and integrated case-management program that incorporates principles of assertive community treatment and combines effective medical and psychosocial interventions and to present the results of a process and outcome evaluation of the program, with particular emphasis on its impact on service utilization and consumer satisfaction. METHOD: Data on demographic, clinical, and several outcome measures were collected on all patients who received care in the program for a minimum of 6 months. For process evaluation we assessed the extent to which the program adhered to its goals and satisfied the patients, their families, and community-service agencies. Outcome-evaluation data on the number and length of hospital admissions were compared for each subject with individual historical data for a period equal to the time spent in the program. In addition, relapses of psychotic symptoms that did not result in hospital admissions were calculated for each patient while in the program. RESULTS: Demographic, clinical, and treatment characteristics of clients show that the program has succeeded in maintaining its focus on providing services to relatively chronically ill patients with psychotic disorders over a mean period of 3 years. The process-evaluation data indicated a high level of satisfaction by patients, families, and other service agencies with the services received. Information on outcome variable showed that the program achieved significantly lower rates of hospital admissions and relapse of psychosis than expected. There was a highly significant reduction achieved in the utilization of inpatient hospital resources for patients receiving care in the program. Most of the inpatient service utilization was attributed to patients either who were resistant to treatment with antipsychotic agents or who refused to accept or comply with medication. CONCLUSIONS: It is possible to provide effective continuity of care from inpatient treatment to community adjustment for most individuals with psychotic disorders across the spectrum by blending hospital and community resources within an integrated case-management model of care.     

Cytokines in rheumatoid arthritis. Potential targets for pharmacological intervention

The ingress of inflammatory leucocytes into the synovium is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Cytokines are mediators involved in the inflammatory events, adhesive mechanisms, angiogenesis and osteopenia associated with RA. Pro- and anti-inflammatory cytokines, growth factors and chemokines all have an important role in these processes. Because the efficacy of currently used antirheumatic therapy is often limited, there is a need for more specific intervention strategies. Anticytokine therapy may include the use of monoclonal antibodies, antagonistic cytokines, soluble cytokine receptors, cytokine receptor antagonists, somatic gene transfer or other approaches. Hopefully, the study of cytokines and their interactions will lead to the development of new immunomodulatory strategies that will benefit patients with RA.     

Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients

The purpose of this study was to investigate the prognostic value of the expression of intercellular adhesion molecule 1 (ICAM-1), leukocyte function antigen 3 (LFA-3), human leukocyte differentiation antigen (HLA)-ABC, HLA-DR, and 5T4 with regard to disease-free survival in Dukes' B and C colorectal carcinoma patients. Forty-one patients (28 Dukes' B and 13 Dukes' C) were entered into this study. Immunocytochemistry was performed on cytospin preparations of enzymatically digested colorectal carcinoma cell suspensions. The frequency of metastases and the duration of disease-free survival were compared between the 25% lowest expressers and the 75% remaining patients for ICAM-1, LFA-3, HLA-ABC, and HLA-DR, and between the 25% highest expressers and the 75% remaining patients for 5T4. Low numbers of ICAM-1-expressing tumor cells were associated with a shorter disease-free survival (P < 0. 001), independent of Dukes' stage. High numbers of 5T4-expressing tumor cells were associated with shorter disease-free survival in Dukes' B patients (P = 0.04). Cox proportional hazard analysis indicated that low numbers of ICAM-1(+) and high numbers of 5T4(+) cells were independent prognostic factors with relative risks of 13. 0 (P = 0.0002) and 4.7 (P = 0.02), respectively. The combination of 5T4 and ICAM-1 marker information identified subgroups of patients with a good (high ICAM-1) or poor (low ICAM-1/high 5T4) prognosis. Neither a lack of HLA-ABC and LFA-3 expression nor the presence of HLA-DR on the tumor cells gave additional prognostic information. These findings demonstrate that low ICAM-1 and high 5T4 expression on tumor cells are prognostic markers, additional to Dukes' stage, for reduced disease-free survival in Dukes' B and C colorectal carcinoma patients.     

Social phobia: a preliminary cross-national comparison

A simple protocol for the growth and differentiation of adult Mongolian gerbil epidermal cells is reported. Insulin (8 micrograms/ml) and reduced levels of serum supplementation (2%) were sufficient for the maintenance of these cells in culture. Primary cultures were maintained as a proliferative monolayer in a medium with low calcium concentration (< 0.3 mM). Terminal differentiation of cultures was induced by raising the calcium concentration (1.6 mM) in the medium. These results support the concept derived from mouse epidermal cell culture that calcium is an important regulator of mammalian epidermal cell growth and differentiation. The present protocol also represents a useful tool for studies of mechanisms involved in epidermal cell growth and differentiation in a laboratory animal.     

Liposome-mediated therapy of intracranial brain tumors in a rat model

PURPOSE: Malignant brain tumors represent a serious therapeutic challenge, and survival often is low. We investigated the delivery of doxorubicin (DXR) to rat brain tumors in situ via liposomes, to test the hypothesis that intact liposomes undergo deposition in intracranial tumor through a compromised blood-tumor vasculature. Both therapeutic effect and intra-tumor drug carrier distribution were evaluated to identify variables in carrier-mediated delivery having impact on therapy. METHODS: The rat 9L gliosarcoma tumor was implanted orthotopically in Fischer 344 rats in the caudate-putamen region. The tumor-bearing rats were treated with DXR, either free or encapsulated in long-circulating, sterically-stabilized liposomes. Anti-tumor efficacy was assessed by survival time. In parallel, liposomes labeled with a fluorescent phospholipid analog were injected into tumor-bearing rats. At predetermined intervals, the brains were perfused with fixative, sectioned, and imaged with laser scanning confocal microscope (LSCM) to investigate the integrity of the tumor vascular bed and the intratumor deposition of liposomes. RESULTS: Free DXR given in 3 weekly iv injections was ineffective in increasing the life span of tumor-bearing rats at cumulative doses < or = 17 mg/kg, and at the highest dose (17 mg/kg) decreased survival slightly, compared to saline-treated controls. In contrast, DXR encapsulated in long-circulating liposomes mediated significant increases in life span at 17 mg/kg. Rats showed a 29% percent increase in median survival, respectively, compared to saline-control animals. The delay of treatment after tumor implantation was a major determinant of therapeutic effect. Fluorescent liposomes were deposited preferentially in tumor rather than normal brain, and were distributed non-uniformly, in close proximity to tumor blood vessels. CONCLUSIONS: Liposomes can be used to enhance delivery of drugs to brain tumors and increase therapeutic effect. The therapeutic effect may arise from release of drug from liposomes extravasated in discrete regions of the tumor vasculature and the extravascular space.     

Clinical improvement after atrioventricular nodal ablation for atrial fibrillation does not correlate with improved ejection fraction

A retrospective review of 15 patients with atrial fibrillation and class III to IV congestive heart failure who underwent atrioventricular nodal ablation demonstrated a marked improvement in their functional abilities. This improvement, however, could not be explained by the improvement in ejection fraction alone.     

Effect of chlorocresol vs caffeine on muscle contracture in malignant hyperthermia susceptible patients

The phenotype of susceptibility to malignant hyperthermia (MHS); can only be detected reliably by the in vitro caffeine-halothane contracture test (CHCT). Enhanced sensitivity of the calcium-induced calcium release mechanism is responsible for the exaggerated contracture response of skeletal muscle fibers from MHS patients to halothane and caffeine. Chlorocresol was demonstrated to be a potent activator of Ca++ release from skeletal muscle sarcoplasmic reticulum. This effect is probably mediated through action on a ryanodine sensitive Ca++ release channel known to be more sensitive in MH. We studied the effect of chlorocresol on the mechanical contracture response of skeletal muscle from patients presenting for the in vitro CHCT. Chlorocresol induces contracture response in a concentration 1/200 of that of caffeine in muscle strips from MH patients. By adding chlorocresol to the protocol of the CHCT, there is clearer discrimination between the responses of MH patients and normal subjects can be achieved.     

Enterocolitis after the surgical treatment of Hirschsprung''s disease: risk factors and financial impact

OBJECTIVE: To determine whether anterograde ejaculation is preserved after transurethral resection of both the prostate and bladder neck (TURP and TURBN). PATIENTS AND METHODS: Between 1994 and 1997, 45 patients (mean age 53.2 years, range 42-62) with bladder neck obstruction and small obstructive adenomas (< 35 g) underwent TURP/TURBN, preserving part of the supramontanal prostate and prostatic urethra for > 1 cm from the verumontanum. They were assessed before and after 0.5-2 years to determine the type of ejaculation, symptom scores and sexual function, and compared with 10 similar patients who had undergone a conventional TURP. RESULTS: With preservation of > 1 cm of the supramontanal prostate, anterograde ejaculation was maintained in 80% of the patients, whereas only one patient in the control group retained anterograde ejaculation. CONCLUSIONS: The preservation of anterograde ejaculation after TURP (in approximately 20% of cases) and after transurethral incision of the prostate (> 90% cases) reported in the literature probably relates more to the presence of an adequate amount of residual prostatic tissue than to the existence of a hypothetical 'pre-prostatic sphincter'.     

Presentation and management of Chiari I malformation in children

To determine the efficacy of operative treatment for children with Chiari I malformation, the medical records and magnetic resonance imaging (MRI) studies of 68 consecutive patients cared for at The Children's Hospital, Boston, Mass., USA, from December, 1988 to November, 1996 were retrospectively reviewed. All patients underwent suboccipital craniectomy, C1 laminectomy, and dural grafting. Bipolar coagulation to shrink and reduce the volume of the cerebellar tonsils was carried out in 40 patients. In 32 of 40 patients with associated syringomyelia, the procedure included placement of a IVth ventricle to cervical subarachnoid space shunt. Twenty-three patients with syringomyelia also had plugging of the obex. There was no operative mortality. Morbidity included a 22% incidence of nausea/vomiting and a 10% incidence of headache, both limited to the immediate postoperative period. Within the first postoperative month, all patients or their parents reported clear improvement in their presenting symptoms and 93% were found to have clear improvement in their presenting signs. In follow-up periods of 6-70 months, all patients had continued unequivocal symptom improvement and all patients were found on examination to have clear improvement in neurological signs. In patients with syringomyelia, MRI studies carried out at least 6 months postoperatively revealed near total or total syrinx resolution in 80% of the cases. This study demonstrates that a standard bony and dural decompression of the foramen magnum region with modifications designed to maximize the restoration of CSF circulation across the foramen magnum is a safe, effective operative treatment for Chiari I malformation in children.