A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients.

In an attempt to devise a screening test for aldosterone-producing adenoma (APA) among hypertensive patients, the serum sodium and potassium levels, plasma renin activity (PRA), plasma aldosterone concentration, and aldosterone-PRA ratio were measured in 348 patients with hypertension. Nine patients with a substantially elevated aldosterone-PRA ratio were selected and hospitalized for further investigations. All nine patients were then recognized by scintigraphy with labeled cholesterol, venography, and surgical excision as having APA. The serum concentration of potassium was subnormal in three of nine patients with APA. In patients with APA, administration of diuretics and salt restriction significantly elevated PRA. However, even under notable diurnal and day-to-day variations of plasma aldosterone concentrations, the aldosterone-PRA ratio was always elevated inappropriately (more than 400) in patients with APA. In contrast, after administration of diuretics, both the PRA and aldosterone levels increased significantly in patients with essential hypertension, but the aldosterone-PRA ratio was less than 200. Since the renin-angiotensin system seems to be a major factor controlling aldosterone secretion in normal subjects, it is suggested that an elevation of aldosterone-PRA ratio more than 400 is a useful screening tool for the prediction of APA among hypertensive patients.

An increase of plasma triiodothyronine concentration in man in a cold environment.

In an attempt to study an effect of cold on endocrine function in man, plasma thyroxine (T4), triiodothyronine (T3), TSH, and cortisol concentrations were studied in 24 healthy men who worked in a cold environment (4 to 6C) for 3 h for the culture of mushrooms and 56 healthy men who lived in cold environment in winter. For comparison, similar measurements were made on 47 university employees who lived in rooms with air-conditioning. In 24 adult men, acute exposure to cold for 3 h failed to affect plasma concentrations of T4, T3, and TSH. In 56 adult men, no significant difference was found in the concentrations of T4, TSH, and cortisol between summer and winter. However, plasma T3 concentration increased significantly in winter, suggesting seasonal variation of T3. In contrast, no such seasonal variation was found in 47 university employees who lived in rooms with air-conditioning.

Difference in pituitary-thyroid feedback regulation in hypothyroid patients, depending on the severity of hypothyroidism.

In an attempt to study pituitary-thyroid interplay during replacement therapy for hypothyroidism, T4 (75-150 micrograms/day) was administered for at least 3 months. A small dose of T4 (75 micrograms/day) significantly depressed basal and TRH-stimulated TSH levels in normal subjects without significantly elevating serum T4 and T3 concentrations. In patients with severe hypothyroidism and marked enlargement of the sella turcica, T4 (2.53 micrograms/kg BW) normalized the serum T4 and slightly elevated the serum T3 but failed to normalize basal and TRH-stimulated TSH levels. In patients with moderate hypothyroidism and moderate enlargement of the sella turcica, T4 (2.0 micrograms/kg BW) normalized serum T4, T3, and basal TSH concentrations but failed to normalize TRH-stimulated TSH levels. In patients with slight hypothyroidism and slight enlargement of the sella turcica, T4 (1.84 micrograms/kg BW) normalized serum T4, T3, and TSH (both basal and TRH stimulated) concentrations. In five patients, an apparent paradoxical increase of basal serum TSH level was found shortly after starting thyroid hormone treatment. It is suggested that pituitary-thyroid interplay during the first 3-6 months of replacement therapy for hypothyroidism varies greatly depending on the severity of hypothyroidism.

Age-related changes in endocrine and renal function in patients with essential hypertension.

Endocrine and renal functions were studied in 149 patients with essential hypertension by measuring plasma electrolytes, renin activity, creatinine and aldoserone, as well as the urinary excretion of creatinine and sodium chloride, before and during treatment for hypertension. Half of the patients responded to trichlormethiazide (thiazide-responsive group) but the other half did not (thiazide-unresponsive group). Systolic and diastolic blood pressures increased progressively uith age in the thiazide-unresponsive group, but were lower and did not progress with age in the thiazide-responsive group. There was no consistent difference in plasma renin activity between the thiazide-responsive and the thiazide-unresponsive groups. The fluctuation of plasma renin activity in response to an excess of sodium chloride or to thiazide treatment was reduced progressively with age. Creatinine clearance decreased and the blood urea nitrogen level increased with age. The age-related decrease of plasma renin activity is discussed on the light of the age-related impairment in the ability of the kidney to excrete sodium and water.

Changes in endocrine activities relative to obesity in patients with essential hypertension.

The possible role of obesity in the development of hypertension was investigated in two study groups. In a population study of 961 subjects, 739 were found to be normotensive and 222 hypertensive. The prevalence of hypertension was 18.7 percent in the nonobese, and 33.2 percent in the obese subjects. Systolic and diastolic blood pressures increased progressively with the increase of relative body weight in both normotensive and hypertensive subjects. In addition, an endocrinologic study was made of 97 patients with essential hypertension; in 82, plasma renin activity (PRA) was inversely correlated with the increase of relative body weight but not with urinary Na excretion. Despite this decrease of PRA, the level of serum aldosterone was not influenced by relative body weight. Thus, the aldosterone/PRA ratio ratio increased progressively with the increase of relative body weight. Thiazide therapy normalized this inappropriately high ratio, and reduced body weight and blood pressure. Restriction of dietary calories and salt intake had a similar effect. With a high-salt intake in an obese subject, the aldosterone/PRA ratio is unduly increased. Apparently aldosterone contributes to the additional retention of sodium and water and thereby promotes hypertension in the presence of an expanded fluid volume.

Changes in hormonal activities relative to the severity of essential hypertension.

Endocrine activity in patients with essential hypertension was studied by measuring the urinary excretion of catecholamines, prostaglandin E (PGE) and cyclic adenosine monophosphate (cAMP). Simultaneously, plasma renin activity, concentrations of serum sodium, potassium, blood urea nitrogen (BUN) and creatinine were determined. Systolic blood pressure and BUN increased progressively with age until the sixth decade. Urinary excretion of norepinephrine was correlated with the systolic blood pressure. In contrast, plasma renin activity and urinary excretion of PGE decreased progressively with the increase in systolic blood pressure. Although the cause of essential hypertension is not known, it is suggested that hypertension accelerates the aging process in the kidney and thus decreases renal PGE synthesis. This decrease of PGE in turn causes a reduction of plasma renin activity, possibly either by accelerating the retention of sodium and water or by failing to stimulate renin synthesis. A decrease of PGE may also potentiate the vasopressor action of norepinephrine.

Inhomogeneous response of expiratory muscle activity to cold block of the ventral medullary surface.

We assessed the effects of cooling the ventral medullary surface (VMS) on the activity of chest wall and abdominal expiratory muscles in eight anesthetized artificially ventilated dogs after vagotomy and denervation of the carotid sinus nerves. Electromyograms (EMGs) of the triangularis sterni, internal intercostal, abdominal external oblique, abdominal internal oblique, and transversus abdominis muscles were measured with EMG of the diaphragm as an index of inspiratory activity. Bilateral localized cooling (2 x 2 mm) in the thermosensitive intermediate part of the VMS produced temperature-dependent reduction in the EMG of diaphragm and abdominal muscles. The rib cage expiratory EMGs were little affected at 25 degrees C; their amplitudes decreased at lower VMS temperatures (less than 20 degrees C) but by significantly fewer degrees than the diaphragmatic and abdominal expiratory EMGs at a constant VMS temperature. With moderate to severe cooling (less than 20 degrees C) diaphragmatic EMG disappeared, but rib cage expiratory EMGs became tonic and resumed a phasic pattern shortly before the recovery of diaphragmatic EMG during rewarming of the VMS. These results indicate that the effects of cooling the VMS differ between the activity of rib cage and abdominal expiratory muscles. This variability may be due to inhomogeneous inputs from the VMS to expiratory motoneurons or to a different responsiveness of various expiratory motoneurons to the same input either from the VMS or the inspiratory neurons.

[Allergic granulomatous angiitis with subarachnoid hemorrhage--a case report].

A case of allergic granulomatous angiitis showing various symptoms of the central nervous system is reported. A 29-year-old female was admitted to our hospital because of severe headache and urinary incontinence. Consciousness was drowsy, and right IIIrd cranial nerve palsy was observed. CT scan revealed subarachnoid hemorrhage, hydrocephalus and arachnoid cyst. Since no aneurysm or arteriovenous malformation was detected by angiography, continuous ventricular drainage was performed. Marked hypertension due to renal vascular origin was suggested by means of laboratory data about serum renin etc., so renal as well as cerebral angiography was carried out by Seldinger's method. There revealed aneurysms of the left renal artery and a branch of the left anterior cerebral artery. Then, ventriculo-peritoneal shunt and resection of left frontal aneurysm were done. Microscopic finding of the excised aneurysm was necrotizing angiitis with infiltration of eosinophil. Six days after the operation, CT scan showed asymptomatic subcortical hematoma at the right occipital lobe. The patient was in good condition and had no cerebral or other complication following steroid therapy. The present case was considered as a very rare one because no case with subarachnoid hemorrhage and cerebral aneurysm due to allergic granulomatous angiitis was reported in the previous literature.

[Relationship between apneic episodes and destruction of temporomandibular joints in patients with rheumatoid arthritis].

There have been only a few investigational reports of sleep apnea syndrome (SAS) in patients with rheumatoid arthritis (RA), although it may not be a rare condition and may be life-threatening occasionally. The factor precipitating SAS in such patients is thought to be destruction of the temporomandibular joints (TMJs) from RA processes. To assess the relationship of the degree of destruction of the TMJs to the frequency of apnea, we examined them in 10 RA patients who complained of snoring. Those patients were classified as classical RA according to the criteria of American Rheumatism Association. They consisted of 3 males and 7 females with a mean age of 57.8 + 11.0 years and a mean disease duration of 15.9 +/- 9.4 years. In order to numerically evaluate the degree of destruction of the mandibular rami, we quoted a method from the literature (Redlund-Johnell I, Scand J Rheumatol 16:355, 1987) and measured the vertical distance (= ramal height) from the mandibular angle to the palato-occipital line on the lateral view film of the cervical spine in each patient. The mean values of ramal height (RH) of the normal material (we studied in Japanese) are 46.0 mm in males and 38.3 mm in females. There were 8 cases of SAS out of the 10 RA patients studied. Their mean total apneic episode (TAE) was 289.9 mm with a range of 0-611. The mean ratio (%) of RH to mean value of the normal material (%RH) was 68.8 +/- 22.2% for all. There was a significant statistic correlation between TAE and %RH (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Small airway involvement in mixed connective tissue disease.

We studied pulmonary functions in 17 female patients with mixed connective tissue disease (MCTD) to detect early pulmonary involvement in this disease; in 8 of the 17 patients follow-up studies were also performed at 1.2- to 5.9-year intervals. In the first pulmonary function tests, decreases in vital capacity (VC) and diffusing capacity (DLCO) were observed in 6 (35%) and 8 (47%) patients, respectively. The ratio of forced expiratory volume in one second to VC was normal in all the patients, but pulmonary resistance and static compliance were abnormal in 6 (35%) and 10 (59%) patients, respectively. However, frequency dependence of dynamic compliance was found in all 16 patients tested. Moreover, 4 (24%) of the 17 patients had normal DLCO and DLCO-to-alveolar volume ratio (DLCO/VA). Reductions in DLCO and DLCO/VA were significantly correlated with the disease duration. These results suggest that small airway obstruction is an early and frequent indication of functional pulmonary impairment, and that impairment of alveolar gas exchange is progressive in patients with MCTD.

Effects of focal cooling of the ventral medullary surface on breathing pattern and blood pressure in dogs.

We assessed the effect of focal graded cooling of the ventral medullary surface (VMS) on breathing pattern and blood pressure in 15 anesthetized, vagotomized and artificially ventilated dogs. Diaphragmatic electromyogram or phrenic neurogram, referred to as Ec, and blood pressure (BP) were obtained during localized (2 x 2 mm2) cooling of the VMS. Greatest depression of both Ec and BP was obtained by cooling in the areas located 4-9 mm caudal to the foramen cecum (Fc) and lateral to the pyramids. Mild cooling in these intermediate areas decreased both inspiratory duration (Ti) and the rate of rise of Ec (Ec/Ti), but respiratory rate was unchanged. Cooling of the rostral areas (0-3 mm from Fc) induced mild depression of Ec amplitude due to reduction in Ec/Ti without changing Ti, and prolonged expiratory duration (Te) significantly. Cooling of the caudal areas (12-18 mm from Fc) reduced Ec amplitude mildly due to reduction in Ti without affecting Ec/Ti, and shortened Te greatly. Cooling of the rostral areas produced mild fall in BP, but cooling of the caudal areas did not affect BP significantly. It is suggested that rostral and intermediate parts of the VMS participate in the shaping of inspiratory drive, whereas wide areas of the VMS including caudal part are involved in the determination of respiratory timing. It is also suggested that the rostral and intermediate parts, and not the caudal part, of the VMS are important in the regulation of vasomotor tone.

Effect of intramedullary procaine injection on tracheal tone and phrenic neurogram.

To map the superficial locations which are involved in the control of respiration and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized, paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial layer (from the rostral part of the trapezoid body to the caudal hypoglossal rootlets and lateral from the pyramids to 5.5 mm from the midline), which included rostral, intermediate and caudal areas, and the area lateral to the hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was decreased by procaine injection to the intermediate area and the area lateral to the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to the intermediate area. In the intermediate area, some injections decreased either phrenic output alone or tracheal tone alone. These results suggest that the two ventral medullary areas, i.e. the intermediate and caudolateral parts, contain neural structures which are involved in the shaping of phrenic output, but only the intermediate area is involved in the regulation of tracheal tone. It is also suggested that, in the intermediate area, the structures responsible for the maintenance of respiration and tracheal tone are, at least in part, separable.

Gastric polyposis caused by multifocal histiocytosis X.

A rare case of gastric polyposis caused by infiltration of Langerhans' cells is reported. A 53 year old Japanese woman complaining of vague abdominal discomfort, was found at endoscopy to have numerous polyps all over the gastric wall. An endoscopic biopsy specimen showed characteristic infiltration of Langerhans' cells in the lamina propria of the mucosa. Functional abnormalities such as impaired gastric acid secretion or malabsorption were not associated with this lesion and the patient was treated conservatively. During follow up over two years, she had a cutaneous eruption with infiltration of histiocytes and osteolytic lesions in the skull. However, no progressive changes occurred in the stomach. This probably benign self-limiting lesion of gastric histiocytosis X may be one of the manifestations of multifocal histiocytosis X, but its aetiology and appropriate treatment have not yet been determined.

Frequency of broncho-bronchiolar disease in rheumatoid arthritis: an examination by high-resolution computed tomography.

Abstract To assess the frequency of pulmonary changes in patients with rheumatoid arthritis (RA), we evaluated a subject group (all outpatients with RA visiting the hospital during a period of three consecutive days) by plain chest radiographs (CRs) and high-resolution computed tomography (HRCT). The study population consisted of 186 patients (32 men, 154 women; mean age 59.8 years), including 6 smokers or exsmokers. Chest radiography was performed on all patients. Seventy (Group A) patients demonstrated abnormal findings and 116 (Group B) did not. HRCT scans were performed on 69 of Group A and 54 of Group B. HRCT demonstrated centrilobular micronodules (n = 29; 23.6%), septal lines (n = 24; 19.5%), subpleural curvilinear shadows (n = 24; 19.5%), bronchiectasis (n = 21; 17.1%), dependent opacity (n = 14; 11.4%), nodules (n = 12; 9.8%), and honeycombing (n = 11; 8.9%). Ten (34%) of the patients with centrilobular micronodules also had bronchiectasis. The most frequent disorder was broncho-bronchiolar disease. Contrary to the CRs finding of no abnormality, HRCT detected pulmonary pathological findings in 40 of 54 patients (74.1%). Pulmonary diseases may be frequently latent, and HRCT is useful in evaluating them in patients with RA.

Re-evaluation of a possible high incidence of hypertension in hypothyroid patients.

In an attempt to re-evaluate a possible high incidence of hypertension in hypothyroid patients, blood pressure was measured in 38 slightly hypothyroid patients, in 17 moderate hypothyroid patients, and in 26 severe hypothyroid patients. The data were then compared with the findings in 73 known euthyroid subjects and in 1,601 possibly euthyroid subjects. Blood pressure and incidence of hypertension increased progressively with age in known euthyroid subjects and in possibly euthyroid subjects. Similarly, blood pressure increased progressively with age in slight and moderate hypothyroid patients, but the incidence of hypertension was high in the sixth decade in slightly hypothyroid patients for some unknown reason. In contrast, blood pressure and the incidence of hypertension were low in the fifth and sixth decades in severe hypothyroid patients. This low blood pressure was elevated slightly when Sv1 + Rv5 and C/T were shifted toward normal by T4 treatment for 3 to 4 months. It is suggested that the hypothyroid state does not accelerate the development of hypertension.