Basal subtype, as approximated by triple-negative phenotype, is associated with locoregional recurrence in a case-control study of women with 0-3 positive lymph nodes after mastectomy.

PURPOSE: Basal subtype, as approximated by the triple-negative phenotype (ER-PR-Her2-), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0-3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy. METHODS: We identified 22 women with 0-3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case-control matched these to 29 women with 0-3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR). RESULTS: On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER-PR-Her2- (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073). CONCLUSIONS: Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.

TbetaR-I(6A) is a candidate tumor susceptibility allele.

We have previously described a type I transforming growth factor (TGF)-beta receptor (TbetaR-I) polymorphic allele, TbetaR-I(6A), that has a deletion of three alanines from a nine-alanine stretch. We observed a higher than expected number of TbetaR-I(6A) homozygotes among tumor and nontumor DNA from patients with a diagnosis of cancer. To test the hypothesis that TbetaR-I(6A) homozygosity is associated with cancer, we performed a case-control study in patients with a diagnosis of cancer and matched healthy individuals with no history of cancer and who were identical in their gender and their geographical and ethnic background to determine the relative germ-line frequencies of this allele. We found nine TbetaR-I(6A) homozygotes among 851 patients with cancer. In comparison, there were no TbetaR-I(6A) homozygotes among 735 healthy volunteers (P < 0.01). We also observed an excess of TbetaR-I(6A) heterozygotes in cancer cases compared to controls (14.6% versus 10.6%; P = 0.02, Fisher's exact test). A subset analysis revealed that 4 of 112 patients with colorectal cancer were TbetaR-I(6A) homozygotes (P < 0.01). Using mink lung epithelial cell lines devoid of TbetaR-I, we established stably transfected TbetaR-I and TbetaR-I(6A) cell lines. We found that, compared to TbetaR-I, TbetaR-I(6A) was impaired as a mediator of TGF-beta antiproliferative signals. We conclude that TbetaR-I(6A) acts as a tumor susceptibility allele that may contribute to the development of cancer, especially colon cancer, by means of reduced TGF-beta-mediated growth inhibition.

CSF amine metabolites, clinical symptoms, and body movement in psychiatric patients.

The relationships between CSF monoamine metabolites (HVA and 5HIAA), nurses' ratings of clinical symptoms, and telemetered measures of motor movement of ten schizophrenic and ten depressed patients were investigated. There was a significant negative correlation between CSF 5HIAA and both agitation ratings and motor movement in the schizophrenics. CSF HVA correlated positively to anxiety and anger in the depressives. The schizophrenics had a significantly higher CSF HVA than the depressives which appeared unrelated to motor movement. The effects of serotonin turnover and arousal in schizophrenia and the association between CSF metabolite gradients, stress, motor movement, and biogenic amine levels in depression are discussed.

Thyrotropin-releasing hormone test and male unipolar depression.

Change in maximal TSH response to a TRH infusion were measured in 18 unipolar depressed males and 2 control groups matched for age, sex, and base-line thyroid status. The mean maximal change in TSH response was significantly lower for the unipolar than the control groups. Clinical and research implications of these findings are discussed. By using a deltaTSH cutoff of 7.0 rather than 5 microIU/ml, 14 rather than 7 depressed patients were correctly identified as having a blunted deltaTSH; 29 rather than 32 to 36 control patients were correctly identified as having a normal deltaTSH score.

Temporal disorganization and primary affective disorder.

The authors used a self-rating scale of thinking process disorganization to measure degree of temporal disorganization in a group of 38 rigorously categorized psychiatric inpatients. Patients diagnosed as having primary affective disorder, depressed type, were significantly different from those with either a character disorder or schizophrenic diagnosis; both schizophrenic and character disorder groups showed variable temporal disorganization scores, and the primary affective disorder group showed consistently high levels of temporal disorganization. Diagnosis was more important than symptom measures in relationship to temporal disorganization scores.

Utilization review of treatment of suicide attempters: chart review as patient care evaluation.

The authors reviewed the charts of 36 nonhospitalized suicide attempters who were identified by utilization review as requiring hospitalization. In 16 of the cases, the authors judged the treatment given to have been adequate because of an absence of a history of psychiatric treatment and/or the rapidity with which outpatient treatment was instiituted. Ten of the cases were judged to have been inadequately treated. This finding pointed to have been inadequately treated. This finding pointed to specific deficiencies in the training of residents and the delivery of psychiatric services and illustrates how chart review can be used to upgrade psychiatric care.

Thyroid function and growth hormone secretion in amitriptyline-treated depression.

The authors studied changes in indices of thyroid function prospectively in a group of 11 patients given amitriptyline to treat depression. The drug caused no significant alteration in these indices, but scores on the Hamilton Depression Rating Scale improved significantly. In another group of subjects with depression, the stimulation of growth hormone secretion by L-dopa was unaffected by amitriptyline therapy.

Utilization review of treatment for suicide attempters.

The authors describe an effort to develop criteria for utilization review of treatment for suicide attempters. Explicit criteria proposed by a panel of experts as essential determinants for hospitalization of these patients were compared with actual clinical practice. It was found that according to the experts' criteria (which were operationalized into rating assessments), over half of the outpatient sample should have been hospitalized. After multiple regression analysis was carried out on the criteria, however, four predictors showed that only 20 percent of the outpatients should have been hospitalized. The authors discuss the issues these findings raise about the criteria of the experts, their utility for research, their validity, and their implications for utilization review.

Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis.

The authors examined the quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the urine of 11 schizophrenic female patients, 14 primary affective disorder (depressed type) female patients, and 10 healthy comparison women. The primary affective disorder patients had significantly less MHPG in their urine than did the comparison subjects. The schizophrenic patients when compared with the healthy subjects or the depressed patients did not excrete significantly different amounts of MHPG in urine. The variance in MHPG in schizophrenic patients was quite large; some had very low urinary MHPG. There was a significant positive correlation between agitation and urinary MHPG for schizophrenic but not depressed patients. The authors discuss theoretical and practical implications of these findings.

Sexual involvement with patients.

Three cases of sexual activity between patients and staff members were presented and determinants and consequences of this type of acting out behavior were discussed. Patients sexual behavior was in part motivated by a need to avoid feelings of loneliness and anxiety and a consequence of the sexual behavior was the recurrence of symptoms and behaviors noted upon admission. The staff members were noted to become more self preoccupied and less involved with both staff and patients following the sexual behavior. The role of the ward psychiatrist in preventing such patient staff interactions includes his taking responsibility for educational and supervisory needs of the staff, his being involved in the creation and maintenance of the ward's moral code and his awareness of group and organizational factors that may impede open staff communications.

Neuroendocrine dysfunction and response to tricyclic antidepressants.

Patients with DSM-III unipolar major depression (N = 26) were treated with tricyclic antidepressants after 2 weeks of inpatient drug-free observation and neuroendocrine testing. Medication was prescribed with individualized dosages and was monitored with blood levels. Treatment response (greater than or equal to 50% decrease in Hamilton depression score after 4 weeks) was seen in 6 of 13 patients given desipramine and 7 of 13 given nortriptyline. Of the 13 nonresponders, 9 accepted treatment with another drug and/or ECT; 5 responded. Thus, 18 of the 26 patients responded to treatment. Abnormal pretreatment DST was correlated with increased responsiveness to treatment, although all patients had a high probability of response.

Racing thoughts in primary depression.

The incidence of and relationship between racing thoughts and clinical variables in primary depression were examined. More than 50% of a group of 32 hospitalized patients reported moderate to severe levels of racing thoughts. Only 13% of patients did not experience racing thoughts. Racing thoughts were significantly related to symptom measures of anxiety, excitation and retardation but not to overall severity of illness or total Hamilton Depression Scale scores. Age but neither sex nor unipolar bipolar classification distinguished patients who did and did not experience racing thoughts.

Clinical correlates of the TRH infusion test in primary depression.

Relationships between clinical measures, diagnosis and neuroendocrine findings were examined in a group of 25 primary depressives maintained drug free on a Neuropsychiatric Evaluation Unit. The TSH response to TRH infusion curves for unipolar and bipolar depressives were significantly different. Agitated patients but not psychomotor retarded patients demonstrated a blunted TSH response curve. No relationships were noted for cortisol hypersecretion and/or loss of diurnality and either diagnosis or psychomotor activity levels in depression. Biochemical and diagnostic implications of these findings are discussed.

The TRH test and urinary MHPG in unipolar depression.

Twenty-five men and 26 women with major unipolar depression were evaluated by the TRH test and urinary MHPG excretion. A significant positive correlation between TSH response to TRH and urinary MHPG was found in the men, though not in the women. These findings suggest that at least for depressed men, central norepinephrine deficiency may be the neurobiological substrate of blunted TSH responses to TRH.

A health care program for hospital staff.

This paper illustrates the significance of one aspect of psychiatric consultation to questions of general hospital health care delivery. The contractual arrangements, implementation, and evaluation of a health care delivery program for nonprofessional hospital employees are presented. Changes in patients' perception of treatment were evaluated by random surveys of representative clinic and ward populations before and after this program was implemented. The program was evaluated by precourse-postcourse questionnaires completed anonymously by the hospital personnel group. The program was found to be successful in generating lists of major health care delivery problems and some possible solutions. The majority of personnel enjoyed and benefited from this program. A conceptual framework and implications of psychiatric consultation for problems of general health care delivery are discussed.

Sociodemographic factors and military psychiatric hospitalization.

This study of race, rank, and psychiatric hospitalization was conducted to provie more information about the impact of social class factors on military inpatient treatment. A retrospective review of the charts of all commissioned officers admitted over a 16-month period along with control groups of airmen and sergeants matche for time of admission was undertaken at a large military training center. Groups were compared on sociodemographic variables (age, race, rank, sex, marital status, length of service, and education background) as well aa clinical variables (referral source, chief complaint, diagnosis, length of stay, and outcome). The implications of briefer hospitalizations for the youngest group of patients (the airmen) are discussed. The over-representation of black enlisted soldiers as psychiatric patients and organizational means of rectifying this situation are discussed.