Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.

BACKGROUND: Although fine-needle aspiration (FNA) is the most sensitive method for the detection of thyroid carcinoma, it cannot provide a definitive diagnosis of malignancy in 60% of the patients operated on for suspicious lesions. Recently, human telomerase reverse transcriptase (hTERT) has been found to be a diagnostic marker of malignancy. We therefore sought to determine whether hTERT gene expression could serve as an adjunct to FNA in the differential diagnosis of thyroid nodules. METHODS: Twenty-four FNA samples from thyroid nodules that were suspected of malignancy were collected. RNA was extracted, and hTERT gene expression was examined by RT-PCR. Cytologic and histologic examinations were also performed. RESULTS: Two of three follicular, three of three Hürthle cell, and eight of eight papillary thyroid carcinomas had corresponding FNA samples that were positive for hTERT. One of two Hürthle cell adenomas was hTERT positive. FNA samples from three follicular adenomas and five hyperplastic nodules were negative for hTERT. Positive and negative predictive values were 93% and 90%, respectively. CONCLUSIONS: The detection of hTERT gene expression in thyroid FNA samples holds promise as a diagnostic marker in the distinction of benign from malignant thyroid lesions. Its application could alter the surgical management of these patients.

The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1.

BACKGROUND: Some experts maintain that (1) > 90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has > or = 94% penetrance by age 50 years. METHODS: We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in 34 patients. MEN1 was defined as (1) endocrinopathy of 2 of the 3 principal related tissues (parathyroid, gastrointestinal endocrine, pituitary) or (2) 1 such feature plus a first-degree relative with MEN1. RESULTS: The initial feature of MEN1 was HPTH in 50%, pituitary tumor in 18%, and gastrointestinal endocrine tumor in 32% of patients, with overall incidences of 82%, 65%, and 74%, respectively. HPTH developed by age 50 years in 73% of patients and by age 70 years in 83%. Penetrance of MEN1 at age 50 years was 82%. Associated features included renal (1) and rectal (1) cancer, malignant thymic carcinoid (1), and malignant pheochromocytoma (1). CONCLUSIONS: Expression of MEN1 can vary considerably from established patterns. In our geographic region HPTH does not routinely precede other features of MEN1 and cannot be used to distinguish affected patients among those at risk. MEN1 can be inapparent until late in life and may be significantly underdiagnosed.

The relationships between premilitary school record data and risk for posttraumatic stress disorder among Vietnam war veterans.

The purpose of this study was to determine whether Vietnam veterans' risk for posttraumatic stress disorder (PTSD) was correlated with their premilitary school performance. The authors compared both primary and secondary school record data on hospitalized chemically dependent PTSD patients with those of both non-PTSD, chemically dependent and community controls. All participants were male Vietnam war combat veterans. The comparisons were made with MANCOVA analyses with the effects of combat and age differences between groups controlled. For the most part, primary-school grade point average, absenteeism, and tardiness data on three groups did not differ significantly. However, the mean secondary school grade points of the future PTSD patients were generally substantially lower than those of controls. Additionally, more secondary school absenteeism and tardiness were reported among future PTSD patients than in the controls. The groups did not differ significantly on number of extracurricular activities. Academic weakness, absenteeism, and tardiness in secondary school appear to be moderately strong predictors of vulnerability to PTSD after traumatization. It also supports the claim that chronic PTSD is, in part, the result of weaknesses present before exposure to trauma.

Prognostic markers in pheochromocytoma.

Clinical and histopathological features do not reliably distinguish between benign and malignant pheochromocytomas. Additional markers that might be useful prognostic indicators in the pathological assessment of these tumors are sought. Immunohistochemical expression of MIB-1, Bcl-2, cathepsin B, cathepsin D, basic fibroblast growth factor (bFGF), c-met, and type IV collagenase were studied on formalin-fixed tissue from 33 nonconsecutive cases of pheochromocytoma, selected on the basis of reliable long-term follow-up, to determine associations with malignancy. The study group included 33 patients, 19 men and 14 women, with a mean age of 45 years, including five cases of neurofibromatosis (NF), three familial, and one MEN IIb. Mean follow-up was 63.2 months. Ten patients were determined to have malignant pheochromocytomas by the presence of metastatic disease. Features found to be associated with malignancy included MIB-1 labeling index (5% vs 1%) (P = .0009), male gender (90% vs 43%) (P = .008), extra-adrenal location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and young age (38 years vs 49 years) (P = .05). None of the five cases with NF were malignant (P = .04). S-100 positivity showed a significant (P = .02) but nonlinear association with benign tumors. Absent S-100 correlated with greater tumor weight. Malignancy was not associated with right versus left side or bilaterality, although bilateral tumors were smaller. C-met, bFGF, cathepsin B, cathepsin D, and collagenase were strongly expressed in most tumors and were not predictive of outcome, nor was bcl-2, which was variably expressed. Using multiple logistic regression with malignancy as the dependent variable, MIB-1 continued to show a significant association with malignancy (P = .005) independent of any association with sex, age, or extra-adrenal location. Using a cutoff value of MIB-1 labeling of greater than 3% yielded a specificity of 100% and a sensitivity of 50% in predicting malignancy.

The efficacies of three relaxation regimens in the treatment of PTSD in Vietnam War veterans.

Ninety male Vietnam veterans with posttraumatic stress disorder (PTSD) were administered relaxation instructions, relaxation instruction with deep breathing exercises, or relaxation instructions with deep breathing training and thermal biofeedback. Improvement appeared on only 4 of the 21 PTSD and physiological dependent variables studied. All 21 Treatment x Time interactions were nonsignificant. This suggests that the treatments were mildly therapeutic, but that the additions of training in deep breathing and thermal biofeedback did not produce improvement beyond that associated with simple instructions to relax in a comfortable chair.

Parathyroid hyperplasia, thymic carcinoid and pituitary adenoma detected with technetium-99m-MIBI in MEN type I.

We report a case of a 57-yr-old woman with history of multiple endocrine neoplasia type I (MEN I). A 99mTc-sestamibi scan demonstrated a hyperplastic parathyroid gland, a large anterior mediastinal mass and a pituitary adenoma during a study done to evaluate recurrent hyperparathyroidism. The importance of this case is that much of the nonparathyroid pathology in patients with MEN I syndrome may be detected with this one study.

A comparison of the symptoms associated with early and late onset alcohol dependence.

This study was designed to determine whether the prevalences of the DSM-III alcohol abuse/dependence symptoms in 87 early and 73 late onset male alcoholics differ from one another. The authors administered a 19-item alcohol abuse/dependence symptom checklist with items based on the DSM-III criteria. Nine of the 19 symptoms were reported significantly more often in the early than in the late onset alcoholics. Antisocial behaviors were reported to have been particularly frequent in the early onset group.

Thyroid carcinoma found at parathyroidectomy: association with primary, secondary, and tertiary hyperparathyroidism.

BACKGROUND: Frequent reports of an association between primary hyperparathyroidism (HPT) and well differentiated thyroid carcinoma, compared with the few reports of associated secondary HPT and thyroid carcinoma, may have implications for different etiologic relationships between the conditions. METHODS: A retrospective review was performed of patients who underwent surgery for HPT between 1975 and 1996 in a single institution. The prevalence of well differentiated thyroid carcinoma diagnosed at the time of parathyroidectomy (PTX) was compared for patients with primary, secondary, or tertiary HPT. RESULTS: There were 845 operations for HPT in 824 patients. Twenty-two patients were found to have thyroid carcinoma at the time of PTX. Thyroid carcinoma was found in 2.6% of the patients with primary and 3.2% of the patients with either secondary or tertiary HPT (P = 0.550). Twenty-one of the patients had papillary carcinoma and 1 had a follicular carcinoma. Eighteen of the carcinomas were < 1 cm in size. A prior history of head and neck irradiation was associated with the diagnosis of thyroid carcinoma at the time of PTX (P < 0.001). Neither renal failure, organ transplantation, female gender, lymphocytic infiltration, nor follicular adenoma of the adjacent thyroid were significant in the association between HPT and thyroid carcinoma. CONCLUSIONS: These data suggest that the association between thyroid carcinoma and HPT is coincidental and possibly related to the closer surveillance of the thyroid gland due to PTX and often concomitant removal of thyroid tissue. Patients with HPT and a history of head and neck irradiation are at increased risk of thyroid carcinoma.

A comparative outcome study of frequent, moderate, occasional, and nonattenders of Alcoholics Anonymous.

The purpose of this project was to identify the outcomes associated with frequent, moderate, occasional, and nonparticipation in Alcoholics Anonymous by male alcohol dependents during the first month after treatment. Informants reported nonparticipants consumed far more alcohol during a 48 week followup than moderate or occasional participants. Moderate and occasional participants were rated as abstinent more often than nonparticipants. Nonparticipants were also reported jailed more often than participants. All other consumption and quality of life comparisons between the groups were nonsignificant. Occasional and moderate AA attendance appear to be associated with better outcomes than nonattendance, but frequent participation was not associated with additional improvement.

Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay.

BACKGROUND: Results of initial operation for sporadic primary hyperparathyroidism are generally excellent, yet today there is pressure to improve outcome and resource utilization. METHODS: We designed a prospective longitudinal cohort study comparing two approaches to concise parathyroidectomy. Strategy A was defined as the palpation method for selective unilateral exploration. Strategy B was defined as the routine use of both preoperative 99mTc sestamibi single photon emission computed tomography (SPECT) imaging and intraoperative quick parathormone assay. With either strategy the study period was 19 months and patients explored unilaterally were candidates for same-day discharge. We compared surgical outcome for 128 consecutive consenting patients each with 6 months or more of follow-up (mean 12 +/- 7.6 months). RESULTS: Demographic, biochemical and pathologic findings did not differ between groups. SPECT imaging precisely localized hyperfunctioning parathyroid tissue. Compared with Strategy A (n = 61), the 67 patients treated by use of Strategy B experienced a higher rate of unilateral exploration (41.0% versus 62.7%, p < 0.00001) and a shorter length of stay (1.07 versus 1.90 days, p < 0.00001) and tended to have shorter operative times, fewer operative failures, and less morbidity. Total perioperative costs did not differ between groups. CONCLUSIONS: Routine use of intraoperative quick parathormone measurement and preoperative 99mTc sestamibi SPECT is as safe, effective, and cost-effective as conventional approaches to parathyroidectomy. Use of this strategy is associated with significant reductions in extent of surgery and length of hospital stay.

Fine-needle aspiration biopsy findings in a case of follicular dendritic cell tumor.

Follicular dendritic cells (FDCs) are non-lymphoid immune accessory cells found in follicles of lymph nodes. Tumors purported to arise from FDCs have recently been described and are considered rare. Histologically, these tumors show an admixture of large, spindled cells and benign lymphocytes. The large cells display a syncytial growth pattern, have delicate chromatin, and, in part, are defined by their expression of complement receptors. The authors recently observed the fine-needle aspiration (FNA) cytologic findings in a case that was subsequently proven to be a FCD tumor. Direct smears exhibited a dimorphic cellular pattern composed of large pale cells admixed with small lymphocytes. The large cells had delicate chromatin, inconspicuous nucleoli, and nuclear membrane infoldings, including occasional cytoplasmic protrusions into the nucleus. The cells were arranged singly and in syncytial groups. These cytologic findings may be characteristic enough to suggest the diagnosis of FDC tumor. Immunocytochemical confirmation should be sought in such cases.

Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT.

PURPOSE: To evaluate the ability to detect and localize parathyroid adenomas with technetium-99m sestamibi single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Forty-seven adult patients underwent Tc-99m sestamibi SPECT. Early (15-30 minutes after injection) and delayed (2-4 hours after injection) images were acquired. Thirty-three patients were examined for initial parathyroid surgery; the remaining 14, for repeat surgery because of persistent or recurrent hyperparathyroidism. SPECT reprojection images viewed in a rotating cine-display mode were read independently by two nuclear medicine physicians who were blinded to the results of other localization studies. Thirty-seven patients underwent subsequent neck exploration. SPECT findings were compared with surgical and histopathologic findings. RESULTS: In the 37 patients who underwent surgery, parathyroid adenomas were confirmed in 34 (92%) and hyperplasia in three (8%). In 31 patients, adenomas were correctly detected and localized with early SPECT images (sensitivity, 91%). In contrast, the sensitivity of delayed SPECT images was 74% (25 of 34 patients) for detection and 32% (11 of 34 patients) for localization. Early SPECT images were significantly better for localization (P < .001) and detection (P = .03). CONCLUSION: For Tc-99m sestamibi parathyroid imaging, early SPECT images were the most accurate in the detection and localization of parathyroid adenomas.

A 48-week natural history follow-up of alcoholics who do and do not engage in limited drinking after treatment.

The research on the controversial Alcoholics Anonymous tenet that limited drinking rapidly leads alcoholics to inebriety is inconclusive. We conducted 48-week follow-ups on 51 posttreatment alcohol dependents who had reportedly engaged in limited drinking and 51 paired controls who apparently had not. According to the informants, the limited drinkers consumed 16 times as much alcohol and were 4 times as likely to regress to unacceptable drinking as controls. They were also more often rehospitalized and attended fewer Alcoholics Anonymous meetings than the controls. They were, however, usually (62%) categorized as abstinent or moderate drinkers when assessed during the follow-up period. The groups did not differ in risk of jailing, detoxification, or job loss, nor did limited drinkers ordinarily regress quickly to inebriety. The outcomes of our limited drinkers were inferior to those of controls but much less negative than those Wilson's Alcoholics Anonymous maintains.

Social maladjustment indicators in PTSD patients' families of origin.

We compared the frequencies with which PTSD patients, psychiatric controls, and hospital employee controls reported that their fathers, mothers, and oldest siblings of each sex had been incarcerated or had received psychiatric/psychological treatment. We also compared estimates of the number of psychiatric hospitalizations, incarcerations, courses of outpatient treatment, treatment sessions, and days of institutionalization undergone by the relatives. Only a chance number of significant differences appeared, which suggests that general psychosocial maladjustment in one's family of origin does not appear to increase trauma survivors' risk for PTSD.

Posttraumatic stress disorder (PTSD) symptoms in PTSD patients' families of origin.

Posttraumatic stress disorder (PTSD) patients, psychiatric controls, and hospital employee controls rated their father, mother, and oldest sibling of each sex on 14 PTSD Interview (PTSD-I) symptom ratings. The stress disorder patients assigned their relatives significantly higher PTSD-I ratings than the control group members did in 35 of 120 comparisons. The number of significant differences was nearly identical in the fathers, mothers, sisters, and brothers. Differences were particularly frequent on items pertaining to intrusive thoughts, impoverished relationships, and guilt. The results suggest that a trauma survivor's risk for PTSD may be related to his family's history for PTSD-like behaviors.

Comparative concurrent validities of five alcoholism measures in a psychiatric hospital.

The concurrent validities of five self-report alcoholism measures were compared in a psychiatric hospital population using Diagnostic Interview Schedule (DIS) alcohol dependence module outputs as criterion. The Michigan Alcohol Screening Test was the most accurate identifier of alcohol dependence at some point in the subjects' life, while the CAGE interview best identified alcohol dependence in the previous year. The correlations of a quantity-frequency measure, the Clinical Signs checklist, and the Medical History questionnaire with DIS alcohol dependence module outputs were generally weaker. The data also suggested that cutting scores based on local norms may offer better hit rates in psychiatric settings than those proposed by the instruments' authors, but additional cross-validations are needed to confirm that possibility.

Effects of a Vietnam War Memorial pilgrimage on veterans with posttraumatic stress disorder.

We compared the scores of Vietnam veterans in treatment for posttraumatic stress disorder on the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder just before, just after, and 6 months after they participated in a pilgrimage to the Vietnam War Memorial in Washington, DC. Significant short-term improvement was reported on Mississippi total scores and on 10 of its 35 items. The number of items showing significant improvement between the initial assessment and the 6-month follow-up did not exceed chance, but significant variance increases appeared on 8 of 35 items. This suggests that the pilgrimage led to a) short-term improvements on several posttraumatic stress disorder symptoms and b) long-term improvements for some participants, but equally large exacerbations for others on a subset of symptoms.

A comparison of combat's effects on PTSD scores in veterans with high and low moral development.

This study was designed to explore the effects of moral development on the relationship between combat intensity and severity of posttraumatic stress disorder. The effect of combat intensity on PTSD Interview total scores and several individual stress disorder symptom ratings was substantial in a Low Moral Development sample, but negligible in a High Moral Development group. These data suggest that moral development may blunt the effect of combat severity on PTSD. These effects were strongest on items that describe reexperiencing of the trauma and exaggerated arousal. Possible interpretations of the results and several caveats were discussed.

A comparison of four PTSD measures' convergent validities in Vietnam veterans.

We compared the convergent validities of four commonly used post-traumatic stress disorder (PTSD) measures in 80 help-seeking Vietnam veterans by contrasting their intercorrelations. When scored as continuous severity or frequency measures, the Mississippi Scale for Combat-related PTSD's and the Post-Traumatic Stress Disorder Interview's (PTSD-I's) concordances with other measures were similar to one anothers' and generally larger than those of either the Diagnostic Interview Schedule (DIS) PTSD module or the MMPI PTSD scale. However, when used only to identify stress disorder's presence or absence, the four techniques' concordances were nearly identical. This suggested that the four measures have similar convergent validities when used simply to identify PTSD, but that the PTSD-I and Mississippi scale offer better convergent validity than the MMPI or DIS instruments when used as severity measures.