Schizophrenic birth seasonality in relation to the incidence of infectious diseases and temperature extremes.

Previous research has indicated that schizophrenics are particularly likely to have been born during the winter months. In the present investigation, we studied the relationships of this birth-seasonality effect to year-to-year variations in the incidences of eight seasonal diseases and climatological temperature extremes in 3,246 schizophrenics. The winter birth-seasonality effect was greater in the years directly following those marked by high levels of infectious disorders than in years directly following those with low incidences of these diseases. Winter diseases (particularly diphtheria, pneumonia, and influenza) appeared to be more involved than others. These effects appeared among unmarried (presumably severe) schizophrenics but not among married patients, suggesting that the relationship is specific to process schizophrenia. The fact that most of the significant and near-significant relationships paired strength of birth seasonality to previous-year disease incidences suggested a prenatal rather than postnatal effect. Birth seasonality did not vary with winter or summer temperature extremes.

Physiologic control of two neurophysins in humans.

Two human neurophysins, nicotine stimulated neurophysin (NSN), and estrogen stimulated neurophysin (ESN) were assayed during physiologic maneuvers and pathologic states in man. NSN is thought to be associated with vasopressin and was elevated in some subjects by volume depletion, surgical stress, hypotension and hypertonic saline infusion. Overnight dehydration did not elevate NSN in spite of urinary concentration. NSN was elevated in some subjects with the syndrome of inappropriate secretion of antidiuretic hormone and when tested was unresponsive to administered water, alcohol or nicotine. ESN was elevated during estrogen administration, in pregnancy, in newborns and in patients with cirrhosis. NSN was also acutely increased at parturition. These data support the association of NSN with vasopressin although changes in NSN were found only with potent stimuli for vasopressin release. ESN may be associated with oxytocin but demonstration of this awaits knowledge of oxytocin physiology in humans.

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.

Functioning oxyphil cell adenoma of the parathyroid gland: a clinicopathologic study of ten patients with hyperparathyroidism.

Adenomas of the parathyroid gland, the majority of which are of the solitary chief cell type, are the most frequent cause of primary hyperparathyroidism. Parathyroid adenomas composed predominantly or exclusively of oxyphil cells are rare and were previously considered nonfunctioning. Among 160 consecutive patients with primary hyperparathyroidism who were explored surgically, ten (6.25 per cent) had adenomas of the oxyphil cell variety. The eight women and two men in this series ranged in age from 28 to 82 years (average, 58 years). The tumors weighed from 0.2 to 4.0 g (average, 1.2 g). Nine of the adenomas were located in the left neck, while the remaining tumor was in the right neck. Histologically, the tumors were composed almost exclusively of transitional and typical oxyphil cells. A residual "capsular" parathyroid composed of chief cells was identified in each case. Electron microscopy, phosphotungstic acid-hematoxylin staining, and the immunoperoxidase technique for cytochrome c oxidase showed the presence of numerous mitochondria in oxyphil cells. All patients had normal serum calcium levels four months to four years (average, 23 months) after removal of the neoplasms.

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.

Involuntary transfer as a cause of death and a medical hospitalization in geriatric neuropsychiatric patients.

The effects of mass involuntary transfer on geriatric neuropsychiatric male patients were evaluated by comparing outcomes for three overlapping sets of patients (N = 403, 385, and 378) over several follow-up periods. One group, the "reorganization" sample, consisted of all patients on three geriatric wards at a time just before the wards were reorganized and 20 percent of the patients were transferred to other buildings. The comparison samples comprised two overlapping groups consisting of all patients on the wards four months earlier and four months later.

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.

Pneumocystis carinii infection presenting as necrotizing thyroiditis and hypothyroidism.

Extrapulmonary Pneumocystis infection has been increasingly reported in patients with acquired immune deficiency syndrome (AIDS), in particular, recently in association with the increasing use of aerosolized pentamidine. This report describes the unusual presentation of extrapulmonary Pneumocystis infection as a thyroid neck mass and clinical hypothyroidism in a 37-year-old man with hemophilia and AIDS. This case differs from the previously reported single case of isolated thyroid pneumocystosis in the presence of a rapidly enlarging neck mass, lack of previous Pneumocystis, and prior prophylaxis with aerosolized pentamidine. The pathologic and electron microscopic description of the peculiar flocculent necrotic thyroid material is contrasted with typical pulmonary alveolar findings in Pneumocystis pneumonia (PCP), the differential diagnoses of a rapidly expanding neck mass, and diagnostic difficulties of hypothyroidism in patients with AIDS are discussed. Finally, it is emphasized that use of aerosolized pentamidine, although successful for prevention of pulmonary PCP, may be insufficient to prevent extrapulmonary infection.

Angiosarcoma of the breast: a report of two cases and a review of the literature.

Angiosarcoma of the breast, a rare tumor with very poor prognosis and insidious early manifestations, frequently is far advanced when first detected clinically. The clinical and pathologic changes in two women with primary, unilateral angiosarcoma of the breast are reviewed and the results are compared with 46 cases already published in the literature. Both patients were middle aged with symptoms for approximately 6 months prior to operation. Both frozen section reports were benign and only called malignant on permanent section. Microscopically the tumors were composed of varying sized, tortuous, elongated vascular channels. The operation varied--a modified radical and a simple mastectomy--and both patients are free from disease 4 and 2 years following operation. It is considered that, in view of the proclivity of this tumor for hematogenous metastases, an axillary dissection may not be justified.

Success of unilateral neck exploration for sporadic primary hyperparathyroidism.

BACKGROUND: Unilateral neck exploration for primary hyperparathyroidism (PHPTH) is controversial because of concern about missed multiglandular disease. METHODS: In patients with sporadic PHPTH our approach has been arbitrarily to surgically explore the right neck first unless preoperative or intraoperative evidence suggests left-sided parathyroid pathologic condition. When an adenoma is identified and a normal ipsilateral gland is confirmed on histologic examination, the contralateral side is not explored. A 15-year series of 371 patients with sporadic PHPTH was reviewed retrospectively to determine the efficacy of this strategy. RESULTS: At operation unilateral exploration was possible in 125 patients (34%). Of these 122 had a single adenoma and two patients had parathyroid carcinoma. One patient with unrecognized hyperplasia required subsequent subtotal parathyroidectomy. There were no major complications. Bilateral surgical exploration was required in 246 patients including 18 with hyperplasia, 4 with double adenomas, and 4 with parathyroid cancer. Bilateral surgical exploration failed in 18 patients (14 persistent and 4 recurrent PHPTH) and was complicated by one recurrent nerve palsy and two cases of permanent hypocalcemia. Operative time was significantly shorter in the unilaterally explored group. CONCLUSIONS: When possible, unilateral exploration for PHPTH is safe and effective, avoids obliterative scarring of the contralateral neck, and may reduce morbidity and operative time.

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.

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.

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.

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

The role of calcitonin and parathyroid hormone in the pathogenesis of post-thyroidectomy hypocalcemia.

Permanent hypocalcemia complicating thyroidectomy is a rare complication, whereas transient post-thyroidectomy hypocalcemia occurs frequently. Ten patients were studied in an attempt to elucidate the underlying mechanisms. An early and transient postoperative rise in calcitonin (CT) corresponding to a decline in calcium levels was demonstrated. Though there was no significant depression of parathyroid hormone (PTH) levels, the failure of the parathyroids to respond to hypocalcemic stimuli suggests a degree of at least transient parathyroid insufficiency. Transiently elevated CT levels appear to play a significant role in the commonly observed early, transient post-thyroidectomy hypocalcemia following subtotal and total thyroidectomy.

Human parathyroid adenoma adenylate cyclase: stimulation by histamine that is blocked by cimetidine.

Recent evidence suggests that the histamine receptor blocking agent cimetidine can decrease parathyroid hormone release from human parathyroids. To determine the mechanism for inhibition we examined the ability of histamine 1 X 10(-5) moles/liter to stimulate adenylate cyclase in a particulate membrane preparation from 13 human parathyroid glands. Histamine significantly increased adenylate cyclase activity as compared to control; however, the degree of stimulation was variable among the individual tissue samples. Enzyme stimulation was dose dependent over the concentration range of 1 X 10(-7) to 1 X 10(-4) moles/liter. Cimetidine at 1 X 10(-4) moles/liter completely abolished the histamine mediated increase in activity, but did not block the epinephrine-induced stimulation. The identification of an adenylate cyclase system in certain human parathyroid adenomas that is stimulated by histamine and blocked by cimetidine may offer a basis for the pharmacologic alteration of parathyroid hormone secretion.

Can and should the ethics of a cottage industry survive?

In an era of rapidly escalating costs of health care, government and the consumer can be expected to play an increasingly active role in determining the character of health care systems. In this setting, professional behavior will become increasingly conspicuous. In reviewing a physician's responsibilities to his patient, to his community, and to himself, emphasis is placed on the pivotal qualities of integrity, selflessness, professional commitment, communication, and continued intellectual and personal growth. Underscroing this a code of ethics that is flexible, comprehensive, and sensitive to the needs of contemporary society.

Schizophrenic birth seasonality and the age-incidence artifact.

Lewis (1989) dismisses a large number of articles in which schizophrenic winter birthrate excesses have been reported as the result of either design problems or the age-incidence artifact. We review about 20 studies in which the effects of age incidence have been controlled in one way or another. The majority support the conclusion that the seasonality effect is due neither to artifact nor deficient research design. We also correct two significant errors in Lewis' description of our prior work.

Concurrent and predictive validity of components of disordered thinking in schizophrenia.

Although the various manifestations of disordered thought have played a central role in diagnostic and theoretical considerations of schizophrenia, such symptoms have not been found specific to schizophrenia, and at best have shown weak relations to outcome. As part of a 7-year followup study of a sample of young, acute, psychotic inpatients, we explored the hypothesis that despite these poor results there might be particular components of disordered thought that might have prognostic utility and be able to discriminate narrowly defined schizophrenics. Using extant symptom scales as our models, we constructed five internally consistent scales of disordered thought from behavioral ratings made using the Psychotic Inpatient Profile--Poverty of Speech, Attentional Impairment, Incoherence, Delusions, and Hallucinations. We tested the ability of these scales to predict various aspects of outcome adaptation including outcome diagnosis. In general, the Attentional Impairment scale demonstrated the best prognostic utility, predicting poorer outcome in several domains. Paradoxically, patients diagnosed by Research Diagnostic Criteria (RDC) as definite schizophrenic at outcome had been rated as showing less attentional impairment than probable and nonschizophrenics. An examination of the pattern of correlations between Attentional Impairment and performance on cognitive tasks suggested that attentional difficulties may be related to different underlying cognitive processes in those diagnosed schizophrenic and nonschizophrenic at outcome by RDC.

Malignant lymphoma of the thyroid gland: a clinicopathologic study.

This study reviews 21 cases of thyroid lymphoma diagnosed between 1969 and 1980. The thyroid gland was the primary site in all but two cases. The 20 patients with non-Hodgkin lymphoma had a mean age of 66 years, 75% were women, and all were Caucasian. A rapidly growing thyroid mass with hoarseness, dysphagia, and difficulty in breathing was the initial finding. Most patients had diffuse histiocytic lymphomas. Associated Hashimoto thyroiditis was found histologically in 57% of the cases. Using the immunoperoxidase stain method on tissue sections, intracytoplasmic monoclonal immunoglobulin was demonstrated in 5 of 15 cases. All but two patients received radiation therapy, and 13 received chemotherapy. The median survival was 8 months; 20% died of unrelated causes and 32% are alive (average duration: 27 months). Dissemination, after local control by radiation therapy, was the leading cause of death. The prognosis was better in men, in patients under the age of 65 years, and in those patients who, on biopsy, did not have involvement of the extrathyroid soft tissue or regional lymph nodes.