Neoadjuvant chemoradiation therapy in patients with surgically treated esophageal cancer.

Over the past 10 years, 232 patients were treated at the East Carolina School of Medicine for cancer of the esophagus. Of these, 73 received neoadjuvant chemoradiation therapy and subsequent surgical resection. The results in this group suggest improved cancer control, with 18 patients (25%) remaining free of recurrence 3 years after treatment, compared with 11 out of 159 patients (7%) in the group that was not treated with neoadjuvant therapy (p < 0.0001). The 5-year recurrence-free survival with neoadjuvant chemoradiotherapy and surgery was 16% (12/73) compared with 3% (5/159) with other types of therapy. Two protocols of neoadjuvant chemoradiotherapy with subsequent surgery were compared: I: Split-course, once-a-day radiotherapy and concomitant cisplatinum/5-fluorouracil followed by esophagectomy. II: Accelerated, twice-a-day radiotherapy with concomitant triple chemotherapy using cisplatinum/5-fluorouracil/vinblastine followed by transhiatal extrathoracic esophagectomy. The survival rate was similar in the two groups of patients but the complication rate was higher in group II. Neoadjuvant chemoradiation therapy and the techniques of transhiatal esophagectomy may have contributed to the improved results in the treatment of esophageal carcinoma. Accelerated radiotherapy with triple chemotherapy was more toxic and did not give better survival rates than split-course, once-a-day, conventional, fractionated-protracted radiotherapy combined with two drugs.

Emergency treatment of acute psychosis.

The author reviews the evolution of emergency psychiatric practice over the past 20 years--from the concept of high-dose antipsychotic medication to the more rational treatment approach for acute psychosis made possible by modern pharmacodynamic insight and the availability of new pharmacotherapeutic agents. A decision tree for current practice in the rapid tranquilization of agitated, apparently psychotic patients is described.

AG337, a novel lipophilic thymidylate synthase inhibitor: in vitro and in vivo preclinical studies.

3,4-Dihydro-2-amino-6 methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride (AG337) is a water-soluble, lipophilic inhibitor of thymidylate synthase (TS) designed using X-ray structure - based methodologies to interact at the folate cofactor binding site of the enzyme. The aim of the design program was to identify TS inhibitors with different pharmacological characteristics from classical folate analogs and, most notably, to develop non-glutamate-containing molecules which would not require facilitated transport for uptake and would not undergo intracellular polyglutamylation. One molecule which resulted from this program, AG337, inhibits purified recombinant human TS with a Ki of 11 nM, and displays non-competitive inhibition kinetics. It was further shown to inhibit cell growth in a panel of cell lines of murine and human origin, displaying an IC50 of between 0.39 microM 6.6 microM. TS was suggested as the locus of action of AG337 by the ability of thymidine to antagonize cell growth inhibition and the direct demonstration of TS inhibition in whole cells using a tritium release assay. The demonstration, by flow cytometry, that AG337-treated L1210 cells were arrested in the S phase of the cell cycle was also consistent with a blockage of TS, as was the pattern of ribonucleotide and deoxyribonucleotide pool modulation in AG337-treated cells, which showed significant reduction in TTP levels. The effects of AG337 were quickly reversed on removal of the drug, suggesting, as would be expected for a lipophilic agent, that there is rapid influx and efflux from cells and no intracellular metabolism to derivatives with enhanced retention. In vivo, AG337 was highly active against the thymidine kinase-deficient murine L5178Y/TK-lymphoma implanted either i.p. or i.m. following i.p. or oral delivery. Prolonged dosing periods of 5 or 10 days were required for activity, and efficacy was improved with twice-daily dose administration. Dose levels of 25 mg/kg delivered i.p. twice daily for 10 days, 50 mg/kg once daily for 10 days, or 100 mg/kg once daily for 5 days elicited 100% cures against the i.p. tumor. Doses required for activity against the i.m. tumor were higher (100 mg/kg i.p. twice daily for 5 or 10 days) but demonstrated the ability of AG337 to penetrate solid tissue barriers. Oral delivery required doses of > or = 150 mg/kg twice daily for periods of 5-10 days to produce 100% cure rates against both i.m. and i.p. implanted tumors. These results were consistent with the pharmacokinetics parameters determined in rats, for which oral bioavailability of 30-50% was determined, together with a relatively short elimination half life of 2h. Clinical studies with AG337 are currently in progress.

Underdiagnosis using SCIDR in the homeless mentally ill.

There are a growing number of studies attempting to diagnose the degree and extent of mental illness among the homeless. Increasingly, these studies are relying on structured diagnostic interviews such as the structured clinical interview for DSM III R diagnosis (SCIDR). This study examines the sensitivity of the SCID in diagnosing major mental illness among the homeless. Comparing SCID interviews with hospital chart diagnosis of twenty-three homeless individuals, the study found that whereas the positive predictive value of the SCID is high in that it accurately predicts a positive diagnosis, its negative predictive power is quite low. A negative SCID diagnosis does not accurately reflect a negative history of mental illness. The study indicates that single point interviews cannot be relied upon to accurately diagnose past history and, therefore, future need for treatment.

Residency training in emergency psychiatry : changes between 1980 and 1990.

Independent random samples of residency training programs were surveyed in 1980 and in 1990 about their emergency psychiatry training. A larger percentage of the programs required daytime emergency service duty in 1990 (80%), compared with 1980 data (50%), and a larger percentage offered a daytime block training rotation, defined as at least 5 days a week of emergency psychiatry for at least 4 weeks (48%), compared with 23% in 1980. Each sample reported that the most important topics in emergency psychiatry were being taught. In 1990, two trends were noted: 1) more faculty psychiatrist time allocated to the emergency service, and 2) more emergency patient visits per shift. In 1990, the residents said they felt more stressed by the heavy patient load and lack of disposition facilities than in 1980, but less stressed by the lack of faculty interest and backup. Based on the data, the interpretation was made that emergency psychiatry training had improved over this period; however, it was indicated that further improvement was also needed.

Axis I disorders in ER patients with atypical chest pain.

To examine the contribution of psychopathology to emergency room (ER) visits for atypical chest pain, we administered two screening measures and the Structured Clinical Interview for DSM III-R (SCID) to thirty-five subjects within seventy-two hours of their ER visit. Follow-up SCID interviews were completed in thirty subjects at five to twelve months. Sixty percent of the sample had an initial Axis I diagnosis, predominately affective (34%) and anxiety (46%) disorders. Forty percent had multiple diagnoses initially. The most common diagnoses were panic disorder (31%) and major depression (23%). At follow-up 47 percent had Axis I diagnoses, 30 percent had multiple diagnoses, with only slightly decreases rates for panic disorder (27%) and major depression (17%). Many subjects had lost, gained, or switched diagnoses by follow-up, in spite of one consistent rater and a few subjects seeking treatment. ER physicians often do not recognize these psychiatric disorders in chest pain patients. The high risk of suicide in panic disorder and depression, and the high cost of disability in recurrent chest pain make it essential that ER physicians include these disorders in the differential of atypical chest pain.

What do police officers really want from the mental health system?

A sample of 309 police officers in Cincinnati and Hamilton County, Ohio, were interviewed about their contacts with mentally ill individuals and about their need for various kinds of information and assistance from the mental health system. During a one-month period, almost 60 percent of the officers had responded to at least one call involving a presumably mentally ill person, and 42 percent had responded to more than one such call. Twenty-two percent had dealt with a presumably mentally ill person who was also mentally retarded. Police officers indicated that they most needed access to information about an individual's past history of violence or suicide attempts, and quick on-site assistance by mental health professionals in assessing suicidal or hostile mentally ill persons.

Clinicians' self-reported reactions to psychiatric emergency patients: effect on treatment decisions.

Masters-level social work clinicians at two urban psychiatric emergency services self-rated their cognitive reactions and conscious feelings toward a total of 783 patients. Negative self-reported affect toward patients was related to their displaying overt psychotic symptoms, having a final diagnosis of substance abuse, being impulsive, unemployed, or having a history of criminal behavior. However, clinicians' reactions did not enter into the model predicting hospitalization, which included opinion of family and friends, degree of psychopathology, suicidal ideation and lack of social supports as the major predictors of whether or not a patient would be hospitalized.

Prevalence of eating disorders in the psychiatric emergency room.

A random sample of 143 patients from a centralized psychiatric emergency service with a catchment area of one million people was studied. A two-stage interview was conducted for diagnosis of DSM-III-R eating disorders. Of those reporting active bingeing, 14.5% were men, and 22.4% were women. No cases of anorexia nervosa were discovered. Bulimia nervosa was diagnosed in 3.0% of the women and 2.6% of the men. Race and marital status were unrelated to bingeing or to any eating disorder diagnosis. Many patients never had discussed their eating behaviors before with a therapist.

What do psychiatric emergency patients really want and how do they feel about what they get?

Psychiatric emergency patients range along a continuum from persons who present to the service with specific requests for help, to individuals who are brought to the service in handcuffs against their will for reasons they do not understand. In addition, studies suggest that psychiatric emergency patients' wishes and expectations often fall outside the traditional framework of psychiatric assessment, are not straightforward or concrete or are not accurately perceived by the clinicians who see them. How these factors impact on patient satisfaction with the treatment they have received is not well-understood, because the manner in which specific patient variables and treatments might relate to patient satisfaction among the psychiatric emergency service population has not been systematically studied. In contrast, psychiatric inpatients and outpatients usually express positive attitudes about their mental health care, although this finding may be skewed by a lack of real anonymity. Chronic patients tend to express less satisfaction with their treatment programs than do others, and patient satisfaction in some studies has been related to patient demographics, diagnoses, treatment histories and patients' global rating of treatment outcome.

Psychiatric disorders of abused women at a shelter.

Thirty physically abused women were randomly selected from the population of a local women's shelter and evaluated by psychiatric interview and psychiatric rating scales. High prevalences of major depression disorder (37%) and PTSD (47%) were determined. Furthermore, these disorders were found to be positively associated. These results suggest the need for immediate availability of psychiatric services at such shelters along with further study of their populations and possible intervention strategies.

The psychiatric emergency service holding area: effect on utilization of inpatient resources.

This study compared the rates of hospitalization from two psychiatric emergency services which were similar except that one service had an extended evaluation unit, or holding area, allowing up to 24 hours of evaluation. The rate of hospitalization from the service with the extended evaluation unit was 36%; the rate from the other service was 52%. The difference in admission rates was related to the availability of the extended evaluation unit, which made it possible for many patients to avoid rather than merely postpone admission to the hospital. Clinical determinants of admission and of successful treatment in the unit were also reviewed.

Substance abuse/mental illness: diagnostic issues.

"Dual diagnoses" of substance abuse and mental illness disorders are common both in psychiatric and substance abuse treatment settings. Recent studies have demonstrated that specific diagnostic categories of mental illness have implications for treatment outcomes of dually disordered patients, but a diagnostic standard has not emerged. The present study compared lay-administered DIS diagnoses with clinical diagnoses of patients in a state hospital treatment program for "dual diagnoses" patients. Categories of DIS diagnoses showed weak association with categories of clinical diagnoses. Several frequent DIS diagnoses were not made clinically and vice versa. Implications for choice of diagnostic instruments to use with this patient population are discussed, as is the potential value of structured assessments in supplementing clinical data.