In premature luteinization, progesterone induces secretory transformation of the endometrium without impairment of embryo viability.

OBJECTIVE: To determine the effect of serum P on endometrial histology in stimulated cycles. DESIGN: Prospective clinical study. SETTING: Community hospital-based donor oocyte program. PATIENT(S): Fertile young oocyte donors and infertile donor oocyte recipients. INTERVENTION(S): Oocyte donors underwent gonadotropin stimulation after midluteal pituitary suppression. Endometrial biopsies were obtained at the time of oocyte retrieval. MAIN OUTCOME MEASURE(S): Endometrial histology and serum P levels in oocyte donors. Pregnancy and implantation rates in oocyte recipients. RESULT(S): Thirteen biopsy specimens (52.0%) showed in-phase mixed proliferative pattern (days 14 to 15), whereas 12 (48.0%) were secretory (days 16 to 17). On the day of hCG, subjects with secretory endometrium had higher P of 1.7 ng/mL (5.4 nmol/L) than women with the mixed pattern (0.8 ng/mL [2.5 nmol/L]). Progesterone > or = 0.9 ng/mL had a 78.6% positive predictive value for secretory transformation. In 75.0% of cycles with secretory endometrium, P was > or = 0.9 ng/mL, (2.9 nmol/L) as early as 2 days before hCG. Both mixed and secretory patterns were associated with similar clinical pregnancy rates (57.1% and 60.0%, respectively) and delivery rates (38.1% and 50.0%, respectively) in recipients. CONCLUSION(S): Subtle elevation of P induced secretory endometrial transformation without reduction in embryo viability.

The nature of the glomerular injury in minimal change and focal sclerosing glomerulopathies.

Glomerular barrier function was evaluated in 12 healthy human volunteers and in 16 proteinuric patients in whom the nephrotic syndrome was associated with alteration of glomerular epithelial cells alone (minimal change nephropathy [MCN]) or in combination with focal glomerular sclerosis (FGS). We determined the glomerular sieving coefficient for each of nine narrow dextran fractions (Einstein Stoke radius [ESR] = 30 to 46 A), and directly measured, or indirectly estimated, values for the determinants of glomerular ultrafiltration. These quantities were then subjected to analysis based on an hydrodynamic theory of solute transport through an isoporous membrane. The results indicate that relative to normal subjects, effective pore radius is reduced from 59 to 55 and 53 A in McN and FGS, respectively; while the ratio, pore area to pore length (a measure of pore density) is correspondingly reduced from 21.7 X 10(6) to 10.1 X 10(6) and 4.7 X 10(6) cm. respectively, We suggest that collapse of the anionic glomerular membrane matrix in these proteinuric disorders may lead to pore shrinkage and reduced pore density, but that reduced electrostatic repulsion of anionic albumin (ESR = 36 A) facilitates its permeation into Bowman's space. The qualitatively similar disorder of glomerular barrier function in MCN and FGS is consistent with a unitary pathogenesis, but may represent a nonspecific response to depletion of glomerular polyanion.

Minimal change nephropathy: an electrochemical disorder of the glomerular membrane.

To investigate the mechanism of proteinuria in minimal change nephropathy, the renal handling of dextrans was studied in seven nephrotic patients with this disorder. Although the urinary excretion of albumin was greatly increased, the urinary excretion and fractional clearance of dextrans (Einstein-Stokes radius (ESR), range 20 to 48 A) were depressed relative to those in nonproteinuric healthy volunteers. This suggests that mean glomerular pore size or pore density was reduced. Uptake of colloidal iron by glomeruli obtained from these patients by needle biopsy was diminished, suggesting loss of glomerular polyanion. Since the fractional clearance of dextrans similar in size to albumin was depressed, not increased, it is proposed that the lack of electrostatic interaction between the glomerular capillaries and polyanionic plasma albumin (ESR = 36 A) accounts for the selective albuminuria which characterizes minimal change nephropathy.

Mediastinal paragangliomas (aortic body tumor): a report of four cases and a review of the literature.

Four cases of paraganglioma originating in the supra-aortic or aortico-pulmonary bodies are described. A review of the reported examples of aortic body tumors and a study of these four cases indicate that there is a high incidence of aggressive tumor growth in the mediastinum, with resultant important morbidity or death in 16 of 35 cases. The morphologic features of aortic body tumors are identical to those of paragangliomas of other locations, and the occurrence of invasive growth and/or metastasis cannot be predicted on histologic grounds.

Benign developmental cysts of the mediastinum.

The examination of 40 benign developmental cysts of the mediastinum from the surgical pathology files supports the previous conclusions in the literature about these lesions. In distinguishing bronchogenic from esophageal cysts, the lining epithelium is not helpful, but the presence of two muscle layers in esophageal cysts and bronchial glands or bronchial cartilage in bronchogenic cysts enables categorization in the majority of cases. Gastroenteric cysts are lined by intestinal epithelium and are further distinguished by their location in the posterior mediastinum and association with other developmental anomalies. Pericardial cysts are histologically characterized by their simple, thin-walled structure, and they are usually closely associated with the pericardium and the diaphragm. A small group of cysts, usually bronchogenic or esophageal in type, cannot be readily classified because they are detached and do not contain helpful identifiable structures. An awareness of the developmental anatomy of the tracheo-bronchial tree and esophagus clarifies the relationships in location and structure that are seen in cysts of this region. All the benign developmental cysts in this series were easily removed at surgery, and there were no known postoperative complications.

Herpetic esophagitis in patients with cancer: ante mortem diagnosis by brush cytology.

Ante mortem diagnosis of herpetic esophagitis has been made in four immunosuppressed patients with cancer. The diagnosis was made by brush cytology at the time of esophagoscopy. All four patients had severe dysphagia unresponsive to nystatin therapy and the diagnosis of herpes infection excluded the use of Amphotericin B for resistant moniliasis. The diagnosis of herpes virus infection of the esophagus has been previously made almost exclusively at post mortem examination. Herpetic esophagitis is shown to be not necessarily a preterminal complication in cancer patients. In three of the four patients the esophagitis resolved as the patients responded to anti-tumor therapy.

Whipple's disease: demonstration by immunofluorescence of similar bacterial antigens in macrophages from three cases.

Although it is widely accepted that Whipple's disease is caused by microorganisms, there is little agreement as to the exact nature of those microbes. Several different types of bacteria have been reported from patients with Whipple's disease causing some workers to speculate that Whipple's disease may be due to a variety of microorganisms. Using an indirect immunofluorescence technique, we have demonstrated bacterial antigens in the granules of the foamy macrophages from three patients with Whipple's disease. The macrophages in each case stained with several types of antibacterial grouping sera. Jejunal biopsies from three normal subjects and one from a patient with celiac-like disease did not show significant reactions with any of the antisera. When these same antisera were reacted with homologous and heterologous bacteria, numerous cross-reactions were seen. However, each organism only reacted with certain antisera resulting in a distinctive pattern of reaction which could identify it. Therefore, if a different organism was present in each case of Whipple's disease, the antisera should give dissimilar reactions from case to case, but if the same type of microbe was present in each case, a similar pattern of reaction should be seen. In fact, the reactions were remarkably similar from case to case. These results suggest that a single, antigenically definable microorganism is present in the jejunal tissue of patients with Whipple's disease.

Renomedullary interstitial cell lesions and hypertension.

The notion that renomedullary nodules of the kidney arise as a response to hypertension was tested. Heart weight, ratio of heart weight to body weight, and blood pressure in 160 patients in whom such nodules were found at autopsy were compared with similar measurements in 160 patients without nodules. There were no significant differences between the two groups, and it was concluded that there was no evidence to support the idea that the renomedullary nodule represents a response to hypertension.

Myocardial lesions of progressive systemic sclerosis. A cause of cardiac dysfunction.

The nature, prevalence, functional significance, and indeed existence of myocardial disease in progressive systemic sclerosis (PSS) has been debated. In this study the clinical and pathological features of 52 autopsied patients were analyzed in an attempt to resolve these questions. A distinctive focal myocardial lesion ranging from contraction band necrosis to replacement fibrosis throughout both ventricular walls was present in 23 patients who had widely patent extramural coronary arteries. There were no morphologic abnormalities of the intramyocardial coronary arteries to account for these lesions. Comparing those patients having severe (13), mild (10), or no (24) PSS myocardial lesions, and patent extramural coronary arteries, there were no major differences in age, sex, frequency and severity of pulmonary, renal or hypertensive disease which could account for the myocardial necrosis and fibrosis. The three groups did differ, however, with regard to clinical cardiac abnormalities: ventricular arrhythmias and conduction disturbances were six and two times as frequent, respectively, in those with severe myocardial PSS compared to the other two groups. A pattern of primary myocardial disease with intractable congestive heart failure resulted from severe myocardial PSS in four patients, angina pectoris with normal coronary arteries was associated with the severe myocardial lesion in three patients, and sudden death in five. The occurrence of contraction band necrosis suggests that the myocardial damage in PSS might be due to intermittent vascular spasm of the type recognized in the digits and possibly kidneys and lungs, i.e., an intramyocardial Raynaud's phenomenon. The findings in our patients clearly show that myocardial progressive systemic sclerosis is a distinct entity with relatively frequent occurrence which may lead to arrhythmias, congestive heart failure, angina pectoris with normal coronary arteries and sudden death.

Carcinoid tumors of the thymus.

Three patients with carcinoid tumors of the anterior mediastinum are described. Study of these patients and an analysis of previously reported cases indicates that the thymus is the primary site of these tumors, which are probably related to the presence of Kulchitsky cells in normal thymus. These neoplasms differ clinically and anatomically from conventional thymomas. They occur predominantly in men, are not associated with myasthenia gravis or red-cell hypoplasia, and are more aggressive tumors than thymomas. Histologically, they are similar to carcinoid tumors of other organs and differ from the variable combination of epithelial cells and lymphocytes of thymomas. Although they are usually locally invasive and frequently metastasize, the clinical course is usually protracted. It is probable that the reported examples of Cushing's syndrome related to thymomas were actually associated with thymic carcinoid tumors.

The endoscopic appearance of the duodenum in Whipple's disease.

Duodenoscopic examination of a patient with Whipple's disease revealed that the duodenal mucosa appeared to be partially covered with a yellow-white material. On closer inspection, however, this was found to consist of enlarged villi interspersed with normal-looking mucosa. Histologically these enlarged white villi were shown to contain a heavy accumulation of lipid and typical PAS positive macrophages. The duodenal mucosa was endoscopically normal and histologically showed only a few PAS positive macrophages one year after instituting antibiotic therapy.

Thymoma: a clinical and pathological study of 65 cases.

A clinicopathologic study of 65 patients with thymomas was performed. The most significant prognostic feature of the thymomas was the presence or absence of gross invasion of adjacent tissue. None of 37 patients with non-invasive thymomas died of tumor or had a recurrence. Invasive thymomas resulted in the death of 3 of 17 patients. Two others are alive with unresectable tumor, and one other patient died of myasthenia gravis with recurrent thymoma. The histologic type of thymoma had no value in predicting prognosis. Thirty-five patients had possibly associated syndromes. These syndromes, particularly myasthenia gravis and red cell hypoplasia, affected survival to an equal or greater extent than did the direct effects of the tumors.

Bronchial carcinoid tumors.

Twenty-eight pulmonary carcinoid tumors were reviewed histologically and clinically. Hematoxylin-and-eosin-stained sections were utilized, as well as special stains, including the argyrophil and argentaffin reactions. The 22 tumors located centrally, at the level of primary or segmental bronchi, had a microscopic appearance distinct from those located more peripherally. One peripheral tumor that was large in size appeared much more aggressive histologically, and was designated an atypical carcinoid. The origin of carcinoid tumors from Kulchitsky cells in the lung, the distinction of peripheral tumors from chemodectomas, and the relationship of bronchial carcinoids to bronchial epithelial hyperplasias and oat cell carcinomas are discussed.

Intravascular angiomatosis: development and distinction from angiosarcoma.

Histologic features similar to those present in angiosarcomas were found in organizing thrombi. Within the thrombi, freely anastomosing small channels, often lined by one or more layers of prominent, occasionally atypical, endothelial cells were noted. Papillary-like projections of organizing thrombus material lined by similar cells heightened the similarity of the process to angiosarcomas. The papillary-like structures appeared to develop due to a combination of endothelialization of thrombus fragments and of ingrowth of interlacing vessels. The peculiar process of thrombus organization, which has been called "intravascular angiomatosis," may be mistaken for true angiosarcoma and thus lead to unnecessary irradiation or radical surgery. The pseudoangiosarcoma differed from angiosarcoma in its confinement entirely within large vascular lumens and in its lack of mitoses, necrosis, and true solid cellular areas devoid of vascular differentiation.

Myxoma-like features of organizing thrombi in arteries and veins.

Evidence for the development of the cardiac myxoma from organizing thrombi has been presented previously. In this study, many of the features of the myxoma were observed in organizing thrombi in arteries and veins. Individual undifferentiated mesenchymal cells, cords of similar cells, vascular bud-like cellular aggregates, fibroblasts, well-formed vessels, and multiwalled vessels set within a loose, mucoid ground substance were present in the thrombi. These areas resembled the basilar layer of the cardiac myxoma. Cartilage-like cells, like those in the superficial zone of myxomas, were noted in some thrombi, and ossification had occurred rarely. These observations support a thrombogenic origin of the myxoma. Local physical factors may provide the stimulus for varying differentiation of mesenchymal cells in both the peripheral thrombi and the myxoma.

Efficacy of pleural needle biopsy and pleural fluid cytopathology in the diagnosis of malignant neoplasm involving the pleura.

A comparison was made of the efficacy of pleural needle biopsy and pleural-fluid cytopathology in the diagnosis of pleural tumor in a group of 271 patients. A malignant tumor involving the pleura was present in 95 cases. Needle biopsy alone provided a diagnosis of tumor in 53 instances, and cytopathologic preparations were diagnostic in 69 patients. A diagnosis was established on either the biopsy or cytopathology, or both, in 86 cases (90 percent). These results indicate the value of using both biopsy and fluid cytology in the evaluation of pleural effusion, which often is due to involvement of the pleura by malignant neoplasm.

Experimental hypertension. The effects of chemical ablation of the renal papilla on the blood pressure of rats with and without silver-clip hypertension.

Because of the ease with which ablation of the renal papilla of the rat can be effected by chemical means, a study was carried out to determine the effects of this ablation on the blood pressure. Significant elevation was found, lennding support to the idea of the antihypertensive role of the renal medulla. Constriction of one renal artery of rats with their papillae removed resulted in a more rapid and greater elevation of pressure than the same procedure in rats ith their papillae intact. The rise in pressure approximated the sum of the rises caused by removal of the papilla alone and by renal artery constriction alone, consistent with the idea of two mechanisms being at work in this model.