Idiopathic multifocal calcification of the ovarian stroma.

We report an apparently unique case of extensive, bilateral, multifocal calcification of the ovarian stroma. The lesion was an incidental finding in a 50-year-old gravida 5, para 5 woman who underwent a hysterectomy and a bilateral salpingo-oophorectomy. Gross inspection revealed ovaries that were of normal size but stony hard. On microscopic examination, the ovarian stroma was extensively replaced by uniformly distributed, spherical foci of calcification that were focally psammomatous. No underlying cause for the calcification, which probably represents an unusual form of dystrophic calcification, could be identified. The differential diagnosis of ovarian calcification, which may arise in diverse conditions, is discussed.

Biosynthesis of indole-3-acetic acid in tomato shoots: Measurement, mass-spectral identification and incorporation of (-2)H from (-2)H 2O into indole-3-acetic acid, D- and L-tryptophan, indole-3-pyruvate and tryptamine.

Indole-3-acetic acid (IAA) and its putative precursors, L- and D-tryptophan, indole-3-pyruvate, and tryptamine were isolated from tomato (Lycopersicon esculentum (L.) Mill.) shoots, identified by mass spectrometry, and measured using capillary gas chromatography with an electron capture detector and radioactive internal standards. Average amounts present were 7.9ng · (g FW)(--1) IAA, 5.7ng · (g FW)(--1) indole-3-pyruvate, 132 ng · (g FW)(--1) tryptamine, 103 ng · (g FW)(--1) D-tryptophan, and 2250 ng · (g FW)(--1) L-tryptophan. Indole-3-acetaldoxime was not found; detection limits were less than 1ng · (g FW)(--1). When tomato shoots were incubated for 6, 10 and 21 h in 30% (-2)H2O, up to four positions in IAA, L- and D-tryptophan, tryptamine and indole-3-pyruvate became labelled with (-2)H. Compounds became labelled rapidly with 10% of IAA molecules containing (-2)H after 6 h. The percentage of labelled molecules of IAA and L-tryptophan increased up to 10 h but then decreased again, correlating with an increase in the total shoot tryptophan and presumably a result of protein hydrolysis in the excised, slowly senescing tissue. The amount of (-2)H in D-tryptophan also showed an increase followed by a decrease, but the proportion of labelled molecules was much less than in L-tryptophan and IAA. Tryptamine became labelled initially at a similar rate to IAA but continued to accumulate (-2)H up to 21 h. We conclude that tryptamine is synthesized from a different pool of tryptophan from that used in IAA synthesis, and is not a major endogenous precursor of IAA in tomato shoots. Indole-3-pyruvate was the most heavily labelled compound after 6 and 10 h incubation (21-h data not available). Furthermore, the proportion of (-2)H-labelled indole-3-pyruvate molecules was quantitatively consistent with the amount of label in IAA. On the other hand, a quantitative comparison of the IAA turnover rate and the rate of (-2)H incorporation into both L- and D-tryptophan indicates that IAA is not made from the total shoot pool of either L- or D-tryptophan. Instead IAA appears to be synthesized from a restricted pool which is turning over rapidly and which has access to both newly synthesized tryptophan and that from protein hydrolysis.

The measurement and mass spectral identification of indole-3-pyruvate from tomato shoots.

Endogenous indole-3-pyruvate has been identified by full-scan combined gas chromatography-mass spectrometry and measured using gas chromatography with an electron capture detector. High specific-activity [5-3H]indole-3-pyruvate was synthesized from [5-3H]tryptophan and used as an internal standard. In order to allow purification of the labile indole-3-pyruvate it was stabilised by the formation in the crude extract of its pentafluorobenzyl oxime derivative. This derivative also allowed sensitive detection and measurement of indole-3-pyruvate in the picogram range using a gas chromatograph with an electron capture detector. Endogenous levels were found to be between 8-10 ng/g f.wt. of tomato shoots which is comparable to that of the indole-3-acetic acid pool size, 11 ng/g f.wt., in this tissue.

Diminished radial count is found only postnatally in Down's syndrome.

Acinar complexity was assessed using the radial count in 23 patients with Down's syndrome. Late intrauterine growth of the lung is not impaired, and acinar complexity is normal. Thereafter, decreased acinar complexity occurs and is grossly and microscopically apparent by 4 months of age. The gross appearance is characteristic, consisting of a diffuse and uniform porosity of the cut surface of the lung. Microscopically, this appearance is due to the presence of dilated alveoli and alveolar ducts. Children and adults with Down's syndrome have a significantly reduced number of alveoli, which are enlarged. In the majority of cases, the alveoli have a double capillary network that has not been described in any other lung condition. No correlation could be established between the radial count and the presence or absence of double capillary network, hypertensive pulmonary vascular disease, or congenital heart disease. The unique appearance of the lung in Down's syndrome results from failure of the lung to develop properly in the postnatal period, presumably genetically determined.

Hypoplasia and immaturity of the terminal lung unit (acinus) in congenital diaphragmatic hernia.

We assessed the maturity of the lungs and the radial count in 10 infants with congenital diaphragmatic hernia who died in the immediate perinatal period. The lungs were all immature, with a histologic appearance of less than stated gestational age. The ipsilateral lungs were less mature in appearance than were the contralateral ones. The radial count, an assessment of acinar complexity, was reduced in all cases, and once again the ipsilateral lung was more affected. We present evidence that, in 4 of 6 lungs, volumes were more reduced than predicted from the radial count, and this may be due to loss of (airway) units. We have discussed the controversy about the appearance of the acinus in diaphragmatic hernia and present reasons to explain this. Hyaline membrane disease often occurs in diaphragmatic hernia, even at full term. Intra-alveolar hemorrhage is a common complication of diaphragmatic hernia.

Increased acinar complexity with polyhydramnios.

We report 4 cases that presented a contradiction in terms of intrauterine lung growth. In all cases there was increased acinar complexity despite an array of influences known to be associated with pulmonary hypoplasia. In 2 of the 4 cases the lungs were severely hypoplastic by weight. Following an analysis of the factors operative in each case regarding lung growth, we conclude that diffuse increased acinar complexity occurs in selected cases with massive polyhydramnios. The observation is of importance because it is consonant with an intimate and dynamic relationship between amniotic fluid volume, lung fluid production, and fetal breathing movements in normal intrauterine lung growth and maturation. Although lung hypoplasia is known to occur in association with polyhydramnios, the reported alterations in lung structure were not previously observed.

Lung growth and development in anencephaly and hydranencephaly.

Significant qualitative and quantitative differences were observed in the lungs of 4 of 6 infants with anencephaly and hydranencephaly. In 3 of 4 of them, the findings were explicable on the basis of the presence of associated congenital anomalies, and in the fourth there was polyhydramnios. The infants with normal lungs did not have associated congenital abnormalities. The absence of the pituitary did not correlate with the degree of development of the lungs. Studies of lung growth in anencephaly and hydranencephaly must clearly note the presence of associated anomalies because anencephaly/hydranencephaly per se may not cause pulmonary hypoplasia in the majority of cases. The most satisfactory assessment in evaluation of lung growth and development was obtained by combining morphologic findings with more than one morphometric parameter. Radial count estimation alone was found to be a poor predictor of lung maturity (morphologic age) in hypoplastic lungs. Radial count and fixed lung volume together provide a better assessment of lung growth and development than does the ratio of lung weight to body weight, which is of use only if severely depressed. The terms immaturity and hypoplasia of the lungs are not necessarily synonymous.

The lungs and causes of death in the nocturnal oxygen therapy trial.

Autopsy findings and a morphometric study of the lungs were compared in 18 subjects receiving nocturnal oxygen and 15 receiving continuous oxygen in the National Heart, Lung, and Blood Institute Nocturnal Oxygen Therapy Trial (about half of those who died). The emphysema score, average interalveolar wall distance, central airway lesions, peripheral airway lesions, and the ratio of weights of left ventricle plus septum to right ventricle were similar in the two groups. The causes of death in the two groups were also similar. This evidence supports the hypothesis that the improved prognosis observed with continuous oxygen therapy nocturnal oxygen therapy in patients with severe chronic airflow obstruction and hypoxemia was due to treatment. There was a trend for there to be more interstitial fibrosis and type 2 alveolar epithelial cell hyperplasia in those treated with nocturnal oxygen; in the hands of one observer, the type 2 cell hyperplasia was significant.

Chronic bronchitis. Correlation of morphologic findings to sputum production and flow rates.

We have assessed bronchial mucous gland size in a group of 26 patients with severe chronic air-flow obstruction and hypoxemia from the NIH Nocturnal Oxygen Therapy Trial. These patients had their sputum volume assessed at least 4 times when free from exacerbations. Mucous gland size was assessed by the gland/wall ratio (Reid Index), by absolute gland area, and by the volume proportion of glands. The volume of sputum produced was significantly related to the volume proportion of mucous glands (Rho = 0.53, p less than 0.01) and to the absolute gland area (Rho = 0.49, p less than 0.05), but not to the Reid Index, (Rho = 0.35, p greater than 0.05). Volume proportion of glands can be easily and quickly measured using a computer-assisted digitizer, and it is the method of choice for measuring mucous gland size in this series. Neither the Reid Index nor the volume proportion of glands was related to the forced expiratory volume in one second (FEV1), and the measurements were not significantly related to each other. The amount of sputum produced was not related significantly to the FEV1 (Rho = 0.26, p greater than 0.05).

Pulmonary hypoplasia in Down's syndrome.

We studied the lungs of seven patients of various ages who had Down's syndrome, to determine whether they had abnormalities in pulmonary development. Six of the seven had hypoplastic lungs. Five had congenital heart disease, but pulmonary hypoplasia was of equal severity, irrespective of the presence or absence or the type of congenital heart disease. Three other patients with congenital heart disease but without Down's syndrome had lungs that were equally diminished in volume. However, these lungs lacked the structural abnormalities seen in Down's syndrome, which consisted of a diminished number of alveoli in relation to acini and enlarged alveoli and alveolar ducts. The patients with Down's syndrome also had a smaller total number of alveoli and a smaller alveolar surface area. We speculate that the smaller alveolar surface area is accompanied by loss of capillary surface area, which is responsible for the aggravation of pulmonary hypertension in Down's syndrome.

The radial alveolar count method of Emery and Mithal: a reappraisal 1--postnatal lung growth.

The radial alveolar count method of Emery and Mithal has been re-evaluated on 76 normal postnatal lungs. Results of reproducibility assessments suggest that each observer should establish normal control values when beginning with the method, and should subsequently use control cases to maintain strict reproducibility. The use of 10 fields per case was found to be inadequate to obtain satisfactory reproducibility, even for a single observer. Prior inflation of the lungs significantly increased the radial counts, and this factor may help to explain the large discrepancy between the results of this study and that of Emery and Mithal. The radial counts correlated well with the chronological age of the child (r = +0.76; p less than 0.001). Alveolarization of the acinus occurs primarily between birth and 2 years; significant but slower growth is seen up to 8 years, after which the results plateau, suggesting that alveolarization is complete. The radial count method appears to provide a relatively simple and reasonably satisfactory assessment of alveolar development, as originally proposed by Emery and Mithal.

The radial alveolar count method of Emery and Mithal: a reappraisal 2--intrauterine and early postnatal lung growth.

The radial count method of Emery and Mithal was applied to the lungs of 37 infants of gestational age 19-42 weeks. The method could be used satisfactorily to evaluate airspace-containing lungs, whether alveolated or non-alveolated (saccule-containing). There was a progressive increase in complexity of terminal lung units throughout gestation, and a smooth transition was effected at 1 month of age between the radial counts of the intrauterine cohort and those of a separate group used to study postnatal lung growth. In the intrauterine and early postnatal group radial count results correlated very closely with the total gestational age (gestational age plus survival time after birth) of the child (r = +0.93). Prior inflation of the lungs affected the radial counts of alveolated lungs much more than those of saccule-containing lungs, so that results correlated most closely with those of Emery and Mithal in the period up to 34 weeks' gestation. Radial count estimation correlated better with total gestational age, crown-rump length, body weight, and fixed lung volume than did any other morphometric parameter assessed. The radial count method provides a reliable index of lung growth in intrauterine and early postnatal development.

Monophasic synovial sarcoma, epithelioid sarcoma and chordoid sarcoma: ultrastructural evidence for a common histogenesis, despite light microscopic diversity.

Ultrastructural examination of six rare sarcomas--four monophasic spindle cell tumours, one epithelioid sarcoma, one chordoid sarcoma--has revealed marked similarities at the electron microscopic level despite widely divergent light microscopic appearances. These features consisted of: 1 the presence of two cell types, viz. a clear cell and a cell resembling the fibroblast; 2 pseudoglandular spaces with projecting microvilli or filopodia, and with related tight junctions; 3 an amorphous intercellular ground substance with focal condensation into recognizable basement membrane. The findings suggest a common maturation of these diverse tumours to synovial-like tissue, and support the proposal of Hajdu Shiu & Fortner (1977) that these be considered variants of synovial sarcoma. Published ultrastructural studies of synovial, epithelioid and chordoid sarcoma are reviewed in the light of these findings. The ultrastructural differentiation of synovial sarcoma from extraskeletal myxoid chondrosarcoma, chordoma and the spectrum of malignant spindle cell tumours is discussed.

Primary pulmonary ganglioneuroblastoma in an adult: maturation, involution and the immune response.

The features of a primary pulmonary ganglioneuroblastoma occurring in an adult are presented. The tumour showed evidence of both maturation and involution. Maturation appeared to be occurring in a centrifugal manner, a rim of mature ganglioneuromatous tissue enclosing the primitive neuroblastoma. Necrosis of the neuroblastomatous element was widespread and associated with deposition in the walls of numerous small vessels of an amorphous eosinophilic amyloid-like material. Accumulation of this material had led to occlusion of some vessels with resultant necrosis of related tumour. A collarette of lymphocytes surrounded the tumour, and lymphocytic aggregates were prominent at the interface between neuroblastoma and ganglioneuroma. Despite widespread vascular invasion, the patient remains well and apparently tumour-free, 2 1/2 years post-resection. The appearances may represent a combined cellular and humoral host response, and a possible relationship of this response to tumour maturation is suggested. The potential role of immunostimulation in the treatment of neuroblastoma is discussed.

Interrelationship of chronic eosinophilic pneumonia, bronchiolitis obliterans, and rheumatoid disease: a hypothesis.

Three patients with histologically proven bronchiolitis obliterans are presented, two of whom had rheumatoid disease. All three patients had, in addition, clinical and radiological evidence of chronic eosinophilic pneumonia; open lung biopsy in two showed coexistent features of chronic eosinophilic pneumonia and bronchiolitis obliterans. The association of both rheumatoid disease are chronic eosinophilic pneumonia with bronchiolitis obliterans in these patients may simply be coincidental, but the striking similarities between the cases suggest that a real interrelationship of these disease entities may exist.

Malignant carotid body paraganglioma: light and electron microscopic study of the tumor and its metastases.

A right carotid body paraganglioma (CBP) was removed from a 30-year-old female after finding metastases to cervical lymph nodes. The tumor and its metastases were studied by light and electron microscopy to determine the neoplastic cell type. Light microscopy confirmed the presence of chief cells but was inadequate alone to exclude sustentacular cells. By electron microscopy, only chief cells were found in both the primary and secondary tumors. This is the first report of an ultrastructural study of a metastasis from a malignant CBP. From our observation, we suggest that CBP be defined as a proliferation of chief and sustentacular cells. Electron microscopy is essential to determine the cell types present and thereby help classify the lesion as a tumor or hyperplasia of the carotid body.