Biomedical subjects
Publications and source records attributed to J F Henry.
For the drug manufacturer the introduction in France of a good clinical practices system will encourage the development of the pharmaceutical industry, provided a number of precautions are observed. These precautions, which include the need for one set of regulations applicable to the whole of Europe and for the training of clinical investigators, are detailed and discussed.
The purpose of this study was to investigate the effectiveness and safety of enalapril in elderly people. A double-blind, randomized, placebo-controlled trial was carried out in 32 subjects aged from 75 to 97 years (mean: 86 years) with blood pressure values equal or superior to 160/90 mmHg. After 8 weeks of treatment with enalapril in doses of 20 to 40 mg/day, the systolic pressure was lowered from 190 +/- 16 to 151 +/- 19 mmHg (P less than 0.0001) and the diastolic pressure from 102 +/- 7 to 85 +/- 11 mmHg (P less than 0.0001). Systolic and diastolic pressures were also significantly reduced in subjects under placebo (from 183 +/- 16 to 165 +/- 21 mmHg, P less than 0.001; and from 101 +/- 9 to 91 +/- 13 mmHg, P less than 0.001, respectively), but the degree of reduction was significantly superior with enalapril (systolic: 39 +/- 25 vs 18 +/- 19 mmHg, P less than 0.005; diastolic: 17 +/- 13 vs 11 +/- 12, P less than 0.001); blood pressure was inferior to 160/90 mmHg in 67% of the subjects treated, as against 35% of those under placebo. Two patients under enalapril died: one on the 27th, the other on the 47th day of treatment. No relation could be established between these deaths and the drug, and this figure of 2 is not significantly different for the number of deaths expected over the same period in a population of that age-group. Among the patients under placebo, one had pulmonary embolism on the 34th day and another had a sudden increase in blood pressure on the 6th day, requiring discontinuation of treatment. It is concluded that enalapril administered alone is effective and well tolerated. Long-term studies are needed to find out whether this angiotensin-converting enzyme inhibitor is superior to a diuretic as initial treatment of arterial hypertension.
The purpose of this study was to test tolerance and the antihypertensive effect of nicardipine, a new calcium antagonist, in 31 elderly patients aged 57-95 years. The study was conducted as a double-blind trial. The patients were allocated randomly to either active or placebo treatment. Sixteen patients were given 10-30 mg of nicardipine three times a day (mean dose, 69.4 mg per day); 15 other patients received a matching placebo. After 4 weeks, nicardipine lowered mean blood pressure, and the changes in systolic and diastolic blood pressure were significantly greater in the nicardipine group than in the placebo group. Nicardipine was tolerated very well, and orthostatic hypotension was never observed. There was no change in heart rate. Plasma renin activity (PRA) was measured in eight patients. There was no correlation between PRA and the antihypertensive effect of nicardipine. A pharmacokinetic study performed in 15 elderly patients showed a fast rate of absorption and also higher plasma levels than those observed in hypertensive adults (mean age, 54 years). This trial demonstrates the effectiveness of nicardipine in elderly hypertensive patients.
Twenty-eight patients with differentiated thyroid cancer presented with local relapse 6 months to 24 years (mean: 7 years) after limited surgery. The tumour was clinically undetectable in 7 cases. Among 22 patients reoperated upon, one died post-operatively, 17.8% had permanent recurrent nerve paralysis and 14.3%, permanent hypoparathyroidism. Metastases were discovered in 15 patients (53.8%), 4 1/2 years on average after the relapse; they resulted in death within less than 2 years in 11 (39.2%) and the survival rate was moderate (26.7%). The mean survival of the 12 patients now in remission is 7 years since the relapse and 13 years since the initial tumour.
Between October 1980 and March 1983 we explored 269 patients who had one or several thyroid nodules with low or normal technetium 99 uptake. Each palpable nodule was aspirated 1 to 3 times, using a fine 21 G2 needle, and the aspirates were immediately spread on glass-plates and kept in alcohol-ether. After staining by the Harris- Shor method, all plates were examined by the same cytologist. Biopsies were unassessable in 50 patients (18%), mainly because they were entirely made up of red cells. Sixty patients did not undergo surgery. In the 159 patients operated upon, cytology was compared with histology which showed 139 benign and 20 malignant nodules. In 5 histologically benign nodules, cytology had shown nuclear abnormalities or enlarged cells suggestive of malignancy (false-positive results: 3.5%). Among 5 nodules diagnosed as benign at cytology, there were 2 papillary microcarcinomas , 2 to 4 mm in diameter, the course of which is little known, 1 well differentiated vesicular cancer extremely difficult to distinguish from vesicular adenoma, and 2 papillary cancers. Fine needle biopsy cytology is a harmless procedure, but it requires considerable experience on the part of cytologists. We consider that it should be performed in all cases of thyroid nodule, either to help in deciding whether or not to operate, or to guide the surgeon in deceding whether or not to operate, or to guide the surgeon in his operative strategy.
Immunohistochemical investigations were carried out on 16 pheochromocytomas for a study of their immunoreactivity to methionine-enkephalin, vasoactive intestinal peptide, somatostatin, corticotropin, beta-endorphin, and calcitonin on serial semithin araldite sections. All antiserums except anti-beta-endorphin, selectively stained a variable number of distinct tumor cells. Methionine-enkephalin-immunoreactive cells were the most frequent. The neuropeptide content of pheochromocytomas appears highly diverse and unpredictable. These findings are supportive of the concept of multisecretory APUD cells of neural crest origin and rule out any of these neuropeptides as reliable immunohistochemical markers for tumor chromaffin cells.
The purpose of this study was to test in double-blind trial the tolerance and antihypertensive effect of nicardipine versus placebo in 32 elderly patients (mean age: 84 years). Nicardipine was given three times a day (mean dose: 69.4 mg per day). After four weeks, nicardipine lowered blood pressure (BP) from 186 +/- 4 mmHg/99.5 +/- 3 mmHg to 150 +/- 6/84 +/- 3 mmHg (p less than 0.001). 10 out of 16 patients were normalized (BP less than 160-95 mmHg). The placebo group remained hypertensive: 181 +/- 7/96 +/- 4 mmHg versus 183 +/- 4/101 +/- 3 mmHg (NS). 3 placebo treated patients were nevertheless normalized. The changes in systolic BP and diastolic BP were significantly greater in the Nicardipine group: respectively -36 +/- 4 versus -2 +/- 6 mmHg (p less than 0.001), -16 +/- 3 versus -5 +/- 4 mmHg (p less than 0.05). Treatment was very well tolerated. Orthostatic hypotension, change in heart rate, variation in biological parameters were never observed. These data agree with Buhler's statement suggesting that calcium channel inhibitors can represent an interesting alternative to diuretics as first line monotherapy in the treatment of hypertension in the elderly.
Results are reported of four and a half years of experience with autotransplantation and cryopreservation of parathyroid tissue in thyro-parathyroid surgery. One hundred patients with hyperparathyroidism secondary to renal insufficiency were treated by total parathyroidectomy and partial autotransplantation, immediate in 98 cases and secondarily using their frozen stored tissue in the other two cases. Results were compared with those in 13 other patients treated during the same period by subtotal parathyroidectomy. Seven of 46 patients with primary parathyroid hyperplasia underwent total parathyroidectomy with immediate partial autotransplantation. Grafts were not used in the other two previously cervicotomized patients. All parathyroid tissue removed during these operations was frozen and stored if not used for grafting. Of 116 patients treated by enlarged total thyroidectomy for cancer, 34 received parathyroid autotransplants; complementary in 19 cases and substitutive in 15. Technique and results are described, and respective indications for autotransplantation and parathyroid cryopreservation discussed with respect to primary, secondary, persisting or recurrent hyperparathyroidism, and to total thyroidectomy for cancer.
Bioavailability of isofezolac, a new non-steroid anti-inflammatory drug, with or without antacid and aspirin coadministration was investigated in 6 healthy volunteer. Each subject received, in random order, isofezolac (50 mg) alone or associated with aspirin (1 g) or phosphalugel (11 g aluminum phosphate). Isofezolac plasma concentrations were salicylic acid by spectrofluorimetric method. Plasma protein binding of drugs was studied by dialysis equilibrium method. During the absorption phase isofezolac plasma levels were slightly decreased in association with isofezolac-aspirin, but bioavailability of isofezolac was not modified. Time to peak of isofezolac was comparable in the three treatments, as was the case with plasma half-lives. Aluminum phosphate did not modify isofezolac availability. Plasma protein binding of isofezolac was very high (99%) and did not influence salicylic acid binding.
A ten year longitudinal survey of 191 female elderly subjects (mean age 80 - Range 61 to 101 years) was set up to demonstrate that even a moderate isolated systolic hypertension is a powerful contributor to the incidence of cerebrovascular complications in the elderly. The incidence of cerebrovascular events was carefully recorded and was correlated with a number of parameters registered at entry into the study. The results show that isolated systolic hypertension as well as diastolic hypertension is significantly correlated to the incidence of strokes independently of other parameters (Blood Cholesterol, Blood Sugar) which do not appear in this population as risk factors of cardiovascular morbidity. This underlines the high interest of controlled therapeutic studies run in this field in elderly patients.
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Autotransplantation of the parathyroid gland was performed in 28 out of 95 patients undergoing total thyroidectomy for carcinoma. The autotransplantation was supplementary in 15 patients who kept at least one parathyroid gland in the neck and substitutive in 12 patients who had total cervical parathyroidectomy. After 1 to 30 months' follow-up none of these patients had signs of hypoparathyroidism. The incidence of permanent hypothyroidism after total thyroidectomy was reduced from 7% to 2.1%. However, autotransplantation should be considered as a means of saving any cervical parathyroid that cannot be preserved and has been shown by histopathological examination to have escaped invasion by the carcinoma.
The authors report their experience of parathyroid autotransplantation in 45 cases of renal insufficiency undergoing hemodialysis. The operation, carried out by two teams, reduces to the minimum the time during which the grafts are exposed to environmental factors likely to impair their function. An immediate anatomopathological examination is necessary to determine the degree of hyperplasia in each gland and the corresponding choice of grafts. The tissue to be implanted must be raised in the least hyperplastic gland and the size of the graft, always difficult to specify, is dictated by the intensity of the hyperplasia. This technique ultimately permits and almost permanent modulation of the parathyroid secretion by action on the secreting tissue. In the event of post-operative persistent hypoparathyroidism, a second operation is desirable, using cryopreserved fragments for the implant. Conversely, in the event of clinical and biological recurrence, the ablation of a precise volume of grafted tissue can be performed without difficulty, under local anaesthetic.
Pharmacokinetics of acebutolol have been studied in hypertensive aged patients (79.4 +/- 3.8 years) and in young healthy subjects (23.4 +/- 0.7 years) after intravenous (0.35 mg/kg bolus) and oral administration (400 mg). Acebutolol and diacetolol, the main metabolite, plasma levels were determined by high-pressure liquid chromatography. After intravenous administration, apparent volume of distribution (1.5 vs. 2.4 liter . kg-1, p less than 0.05) and total body clearance (6.2 vs. 8.8 ml . min-1 . kg-1, n.s.) of acebutolol are smaller in elderly than in young men. After oral administration, maximum plasma levels (28.03 vs. 9.68 micrograms . l-1 . kg-1) and area under the curve (163.1 vs. 57.5 micrograms . l-1 . h . kg-1) are significantly higher in aged patients than in young subjects (p less than 0.001). Acebutolol and diacetolol plasma half-lives increase in elderly patients (11.6 vs. 7.2 h and 14.8 vs. 12 h respectively). These results suggest a possible accumulation of acebutolol and diacetolol in elderly.
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1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.
A ten year longitudinal survey of 191 female elderly subjects (mean age 80--Range 61 to 100 years) was set up to demonstrate that even a moderate isolated systolic hypertension is a powerful contributor to the incidence of cardiovascular complications in the elderly. The incidence of all cardiovascular events was carefully recorded and was correlated with a number of parameters registered at entry into the study. The results show that isolated systolic hypertension as well as diastolic hypertension is significantly correlated to the incidence of strokes and myocardial infarction independently of other parameters (Blood Cholesterol, Blood Sugar) which do not appear in this population as risk factors of cardiovascular morbidity. This underlines the high interest of controlled therapeutic studies run in this field in elderly patients.