Prolactin secretion in acromegalic patients before and after selective adenomectomy.

PRL secretion before and after transsphenoidal adenomectomy was studied in 13 patients with acromegaly. Six patient had elevated basal serum PRL levels before surgery, while 7 patients had normal levels. In every patient, the basal serum GH level decreased to less than 5.0 ng/ml after surgery. In the group (group A) with high basal serum PRL levels (mean +/- SD, 41.3 +/- 5.8 ng/ml) before surgery, the PRL levels decreased significantly (P less than 0.0002) to less than 10.0 ng/ml (4.8 +/- 3.6 ng/ml) after the operation. However, in the group (group B) with normal levels (10.8 +/- 4.4 ng/ml) before surgery, PRL levels changed little (7.8 +/- 3.1 ng/ml) after the operation. In group A, the increment of PRL after TRH injection decreased or disappeared (P less than 0.02; 4.1 +/- 2.4 ng/ml) after surgery compared with that before surgery (39.2 +/- 25.9 ng/ml). On the other hand, in group B, the increment of PRL after TRH injection was nearly unchanged (17.1 +/- 7.0 ng/ml) after surgery compared with that before surgery (19.3 +/- 8.0 ng/ml). The results indicate that PRL is secreted from the pituitary adenoma in acromegalic patients with hyperprolactinemia, while PRL secretion from the normal part of the pituitary gland is decreased.

Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy.

Patients with acromegaly have alterations in mineral metabolism. To determine the effect of correction of excess GH secretion on calcium metabolism, we studied 12 acromegalic patients before and 3-4 weeks after pituitary adenomectomy. Treatment of acromegaly resulted in significant decreases in both serum calcium [from 9.3 +/- 0.2 to 8.7 +/- 0.1 mg/dl (mean +/- SEM); P less than 0.01] and urinary calcium excretion (from 200 +/- 24 to 88 +/- 12 mg/24 h; P less than 0.0002). Serum phosphate also decreased significantly (P less than 0.01) from 4.8 +/- 0.2 to 4.3 +/- 0.2 mg/dl. Both serum immunoreactive PTH and calcitonin levels were normal initially and did not change after surgery. The mean serum 25-hydroxyvitamin D (25OHD) level was significantly (P less than 0.01) lower and the 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was significantly (P less than 0.0001) higher in acromegaly compared with measurements in 25 normal subjects. After surgery, the serum 25OHD level did not change; however, the serum 1,25-(OH)2D concentration fell significantly (P less than 0.0001) from 60 +/- 4 to 43 +/- 2 pg/ml. A positive correlation was found between the decrements in urinary calcium excretion and the serum 1,25-(OH)2D level when the comparison was made between the decrements as percentages of pretreatment values (r = 0.64; P less than 0.05). The accumulated data suggest that the hypercalciuria in acromegaly might be due to intestinal calcium hyperabsorption, which could be attributed to the elevated circulating 1,25-(OH)2D level. Excessive GH secretion might stimulate the production of 1,25-(OH)2D and might also directly stimulate calcium absorption.

Alterations in mRNA expression of duodenal 1,25-dihydroxyvitamin D3 receptor and vitamin D-dependent calcium binding protein in aged Wistar rats.

Previously, we reported that uptake of calcium into isolated duodenal cells and duodenal brush border membrane vesicles decreased in senescence. Decreases in duodenal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor number and 9k vitamin D-dependent calcium binding protein (CaBP) were also observed in aged rats. In this study, we examined the steady state mRNA levels of duodenal 1,25-(OH)2D3 receptor and CaBP in both adult (6-month-old) and old (24-month-old) rats. We identified one major band of 4.4 kb for 1,25-(OH)2D3 receptor mRNA. The size of the transcript was not affected by age. The content of 1,25-(OH)2D3 receptor mRNA (normalized with poly(A)+RNA) decreased 23% in the aged rat as compared to the adult rat. The expression of CaBP was also examined. A single band of 0.6 kb was observed for CaBP mRNA. The size of CaBP mRNA was not altered with age. However, the abundance of CaBP mRNA (normalized with poly(A)+RNA) was reduced 20% in the senescent rat. Thus, the results in the present study were consistent with our previous findings that the number of 1,25-(OH)2D3 receptors and the level of CaBP declined in the aged rat. However, the precise mechanism leading to the age-related deficit in mRNA expression remains to be elucidated.

Inverse relation between severity of psoriasis and serum 1,25-dihydroxy-vitamin D level.

The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal levels of these serum parameters were within the normal range. ASI and SI showed significant inverse correlations (r = -0.387, P less than 0.05 and r = -0.638, P less than 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them.

Use of a temporary caval filter in a young man with pulmonary embolism to prevent migration of massive caval thrombus during an attempt of caval thrombolysis.

A 33 year old male with no known risk factors for hypercoagulability developed a massive thrombi in the inferior vena cava (IVC). The patient had a history of both pulmonary embolism and embolism related syncope. The thrombus which extended proximally to the level of the renal vein and distally to the left superficial femoral vein did not respond to anticoagulant therapy or thrombolysis. Thirteen days after admission, we decided to use a temporary caval filter to provide protection from migration of the thrombus while attempting invasive thrombolytic therapy, which was performed using a tissue type plasminogen activator through a coaxial catheter of the temporary filter. This resulted in a marked decrease in the size of the thrombus, and multiple thrombi were found to be trapped in the temporary filter. Although the temporary caval filter was effective in capturing emboli, resulting in a decrease in the thrombus size, the thrombus was not completely dissolved within two weeks, which is the maximal implantation time. A permanent filter was eventually used to prevent pulmonary embolism, which could arise from the remaining thrombus. We have found placement of a temporary caval filter to be a safe and effective adjunct, in select cases, when attempting thrombolysis of massive thrombi in the IVC. Since we inserted the temporary filter 13 days after admission, use of a temporary filter during thrombolysis may have been more effective if conducted earlier in our patient's clinical course.

Participation of both intracellular free Ca2+ and protein kinase C in tonic vasoconstriction induced by prostaglandin F2 alpha.

The roles of intracellular free Ca2+ and protein kinase C in the tonic contraction induced by prostaglandin were studied. Prostaglandin F2 alpha induced tonic contraction of rat thoracic aorta in both control and Ca2(+)-free solution. Close correlations were observed between the contractile response of aortic strips and the changes in intracellular free Ca2+ concentration in vascular smooth muscle cells assessed with the fluorescent Ca2+ indicator fura 2, both in control and Ca2(+)-free solutions. Prostaglandin F2 alpha also enhanced the production of inositol 1,4,5-trisphosphate in vascular smooth muscle cells before the rise of the intracellular free Ca2+ concentration. Moreover, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, inhibited the tonic contractions induced by PGF2 alpha and 12-O-tetradecanoyl phorbol-13-acetate, a direct activator of protein kinase C, at similar concentrations. These results suggest that both intracellular free Ca2+ and protein kinase C participate in prostaglandin F2 alpha-induced tonic contraction.

Effect of elastase in reversing the de-differentiation of rabbit costal chondrocytes in culture induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA).

As elastase is known to affect cell functions in various cell systems, its effects on the functions of control and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated chondrocytes in vitro were examined. Pretreatment of chondrocytes with TPA (10(-8) M) for 48 h significantly enhanced DNA synthesis, inhibited glycosaminoglycan (GAG) synthesis and inhibited the increase in ornithine decarboxylase (ODC) activity in response to parathyroid hormone (PTH) relative to values in control cultures. Addition of elastase (1, 10 and 50 ng/ml) for 24 h partially inhibited the de-differentiated phenotypes induced by TPA such as the decreased synthesis of GAG and decreased response of ODC activity to PTH without affecting the DNA synthesis. Moreover, elastase significantly increased both the basal level of cyclic AMP and that on PTH treatment of TPA-pretreated cells. These results suggested that elastase partially restored the differentiated phenotypes of de-differentiated chondrocytes probably through its effect in increasing the level of intracellular cyclic AMP.

[A case of polymyalgia rheumatica with swelling and pitting edema of the distal lower extremities].

We report a case of an 82-year-old woman with polymyalgia rheumatica (PMR) associated with swelling and pitting edema of the lower extremities. The patient had been previously admitted because of PMR in 1990, but there was no history of swollen extremities. In July 1996, at another hospital, she was again diagnosed as having PMR on the basis of pain in the neck, shoulders and lower back. Administration of prednisolone was followed by improvement of the symptoms. Four months later, similar pain recurred and swelling of the lower extremities was noted. On admission, the erythrocyte sedimentation rate was 86 mm/h, and C-reactive protein was 15.5 mg/dl. Reviewing the previous treatment, it was ascertained that her clinical deterioration was due to premature reduction of the steroid dosage. The cause of the swelling of the lower extremities was unlikely to be heart, liver, kidney or endocrine disease. Prednisolone was increased from 2.5 mg to 10 mg daily with marked improvement in all the symptoms including the swelling and pitting edema. In 1996, a study reported distal extremity swelling with pitting edema as a manifestation of PMR, which mostly developed concurrently with proximal symptoms or during relapses of PMR. The swelling responded poorly to non-steroidal antiinflammatory drugs but promptly to corticosteroids. The distal swelling was reported to be tenosynovitis and synovitis of the surrounding structures. The present case appears similar to that report. More studies of PMR need to be done.

[Comparison of hypotensive effects of acutely administered human parathyroid hormone (1-34) in normal young and elderly subjects].

The effects of acute administration of human parathyroid hormone (1-34) [PTH(1-34)] on the blood pressure of 15 young (mean age +/- SD, 20.9 +/- 1.7 years; 7 males and 8 females) and 11 elderly (78.1 +/- 5.9 years; 4 males and 7 females) normal subjects were compared. The elderly subjects have a slightly, but significantly higher mean basal systolic blood pressure (132.4 +/- 17.7 mmHg) than the young subjects (118.7 +/- 11.4 mmHg), but the basal diastolic and mean blood pressures of the two groups were similar. Intravenous bolus infusion of PTH(1-34) at a dose of 100 U induced transient, but marked hypotension in all subjects. The mean maximal decrease in systolic blood pressure (-delta SBP was significantly more (p less than 0.01) in the elderly subjects (42.5 +/- 13.9 mmHg) than in the young subjects (8.0 +/- 8.9 mmHg), but the maximal decrease in diastolic blood pressure (-delta DBP) was similar in the elderly (25.6 +/- 13.9 mmHg) and young (27.3 +/- 10.9 mmHg) subjects. The maximal decrease in the mean blood pressure (-delta MBP) was also significantly higher (p less than 0.01) in the elderly subjects (31.9 +/- 8.7 mmHg) than in young ones (20.6 +/- 7.6 mmHg). The corrected serum level of calcium (scCa) was significantly (p less than 0.01) lower in the elderly subjects (9.6 +/- 0.2 mg/dl) than in the young ones (10.0 +/- 0.3 mg/dl), and the serum level of C-terminal parathyroid hormone (C-PTH) was significantly higher in the elderly subjects (270 +/- 80 pg/ml) than in the young ones (150 +/- 80 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

[Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia].

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.

[An analysis of questionnaires about geriatric medicine/medical education sent to members of the Japanese Society of General Medicine].

Geriatric medical care can be viewed as general medical care for the elderly. We conducted a survey of members of the Japanese Society of General Medicine who belong to a university hospital, on their views of geriatric medicine/medical education. The questionnaires consisted of six categories of items about: (1) the physician's career; (2) whether the physician performs geriatric research in his/her laboratory; (3) whether the physician has an interest in geriatric medicine or medical education; (4) the physician's views on geriatric medicine or medical education; (5) of what pre- and post-graduate medical education on geriatric medicine should consist, from the physician's point of view: and (6) the physician's ideas about geriatric medicine/medical education in view of general medicine. Out of the 181 questionnaires sent, 96 (53%) people replied, of whom 51 (53.1%) were members of a Department of General Medicine, 57 (60%) were teaching staff, 46 (48.4%) had experience in home medical care such as home visits, and 17 (18.1%) belonged to the Japanese Society of Geriatric Medicine. Seventy-six respondents (85.4%) had an interest in geriatric medicine/medical education. Of the respondents, 96.8% recognized the need for pre- and post-graduate medical education concerning geriatrics. Some members of the Japanese Society of General Medicine who answered the questionnaire see geriatric medicine as entirely general medicine, and also that geriatric medicine is important, necessary and special. In addition, they see that the field of geriatric medicine is not yet developed in regard to geriatric medical care and education. Most respondents could not specify which section in a medical university is responsible for teaching the fields of basic and social medicine. This result shows that it may be difficult to incorporate pre-graduate geriatric medical education into the curriculum. As part of the pre-graduate curriculum of medical education on geriatrics, a practical exercise such as inspection of a geriatric hospital and geriatric home was considered most desirable by the respondents. Out of nine items, the top three most important aspects of post-graduate medical education on geriatrics for clinical and social medicine, were (1) studying the medical care and welfare of the elderly, (2) assessing the impaired life function of the elderly, and (3) studying pharmaco- therapy. Out of 6 items, the top three most important aspects of a practical exercise in post-graduate medical education in geriatrics were (1) providing general care to the elderly, (2) giving rehabilitation guidance and (3) providing psychological support for the elderly. Furthermore, 20 of the respondents (22.5%) have performed geriatric medical research on either the activities of daily life of the elderly or living wills, both of which seem to reflect the health and life of elderly people.

[Cognitive function and calcium-related factors in elderly female subjects].

Calcium (Ca)-related factors were evaluated as possible related factors to senile dementia in 60 elderly female subjects (mean age +/- SD: 79 +/- 7 years). These subjects were classified by their score on Hasegawa's Dementia Screening Scale, into a non-dementia group (score 22-32.5, n = 18) and a dementia group (0-21.5, n = 42), and the latter group was further classified by ischemic score into Alzheimer-type dementia (n = 22) and vascular-type dementia (n = 20). There was no significant difference in the mean values of age or serum creatinine among the three groups. In the Alzheimer-type dementia group, the mean serum level of Ca was significantly lower, and the serum level of parathyroid hormone (PTH) and urinary Ca were significantly higher than those in the non-dementia group, respectively. In the group of vascular-type dementia, the mean serum level of calcitonin (CT) was slightly, but not significantly, lower than that in the non-dementia group. The score for cognitive subjects negatively correlated significantly with the values of serum PTH (r = -0.49, p less than 0.05) and urinary Ca excretion (r = -0.38, p less than 0.05), respectively, and positively correlated significantly with that of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] (r = 0.31, p less than 0.05), in the combined group of non-dementia and Alzheimer-type dementia, and positively correlated significantly with the serum CT level (r = 0.40, p less than 0.05) in the combined group of non-dementia and vascular-type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)