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We performed a study in 92 diabetic patients (76 Type 1 and 16 Type 2) without retinopathy to determine the relation between diabetic dyschromatopsia and neuropathy, which has been evoked in previous studies. Color vision was explored with Lanthony's desaturated D 15 panel. Peripheral nervous function was explored with an electrophysiological score which has been beforehand validated. Moreover evoked visual potentials were performed in 38 diabetic subjects in order to determine whether dyschromatopsia was related to an impairment of central optic pathways. Fifty-one among the 92 diabetic subjects had a blue-yellow dyschromatopsia. Among the recorded parameters, only peripheral nervous impairment was significantly more frequent in the group with dyschromatopsia than in the group without. Ten among 38 diabetics had impairment of the evoked visual potentials. Frequency of alteration of evoked visual potentials was not different between the group with and the group without dyschromatopsia. Our results confirm the relationship between dyschromatopsia and the alteration of the nervous function in diabetic subjects. In return, lack of significant modification of evoked visual potentials among diabetic patients with dyschromatopsia and the blue-yellow axis of dyschromatopsia are in opposition with a direct neurological origin of dyschromatopsia. We therefore evoke a common process in the beginning of the diabetic dyschromatopsia and of peripheral neuropathy.

This study was a 6-month open trial of the effects of naftidrofuryl fumarate (600 mg/day orally) on the clinical and electrophysiological signs of diabetic polyneuropathy in 15 patients. A scored clinical evaluation and an indexed electrophysiological examination were done at inclusion, and after 3 and 6 months. Mean clinical score and electrophysiological index was improved after 3 months of therapy, the improvement persisting at 6 months, with no change in control of diabetes. These results could be related to the vasodilating properties of the drug, causing an increase in nerve temperature, or to a specific neurotropic action, as recently demonstrated in rats. Controlled studies are necessary to confirm these results, and explore the mechanism of this improvement.

Diabetic dyschromatopsia is frequent and is a true complication of diabetes mellitus. Causative factors other than retinopathy have been suggested, but they remain unclear. We have explored the color vision of 100 diabetics aged 16 to 65 (88 insulin-dependent, 12 non-insulin dependent) with Lanthony's D15 desatured panel. Degenerative complications were looked for, especially by fundoscopy and electrophysiological exploration of peripheral nerves using specific scoring. 73% of the diabetics had dyschromatopsia. Dyschromatopsia was significatively more frequent when retinopathy was present (26 out of 30 diabetics with retinopathy versus 47/70 without). We explain the absence of a strict parallelism between dyschromatopsia and retinopathy by the intervention of other factors. Whereas the equilibration of the diabetes was not different between the groups with or without dyschromatopsia, patient age, microalbuminuria, blood pressure and alcohol intake were higher in patients with dyschromatopsia. The greater prevalence of peripheral neuropathy in patients with dyschromatopsia, confirmed by electrophysiology, and independently from the existence of retinopathy, is an indicator of the existence of neuronal disease, whose level remains to be determined. Our results are the indispensible preliminary step to a study of the respective importance of these pathogenic factors.

This study examined the relationship between uteroplacental blood flow and fetal hypotrophy in streptozocin-induced diabetic rats (40 mg/kg body wt i.v.). Our results showed that, in diabetic rats, fetal hypotrophy was associated with a significant reduction in arterial blood velocity in the uterine artery (P less than 0.001), placenta (P less than 0.01), umbilical artery (P less than 0.01), and fetal aorta (P less than 0.05). This was not observed when diabetic rats were treated with insulin. Treatment of rats with the alpha 1-blocking vasodilator nicergoline restored fetal growth and arterial blood velocity to control values without affecting the degree of hyperglycemia. Nicergoline in control rats did not change fetal weight and caused only minor hemodynamic changes on presumably already maximally vasodilated arteries. We concluded that the uteroplacental hemodynamic disturbances observed in diabetic rats play a major role in the establishment of fetal growth retardation.

The aim of this study was to determine if placental prostanoids could mediate the vasodilating action of an alpha-1-adrenoceptor antagonist, nicergoline (400 micrograms/kg i.p.), during late pregnancy in streptozotocin-induced diabetic rats (40 mg/kg i.v.). Placental prostanoid concentrations were evaluated by radioimmunoassay. Prostaglandin E2 levels showed a highly significant increase in diabetic and nondiabetic rats treated with nicergoline (p less than 0.001). 6-Keto-PGF1 alpha concentrations were slightly increased in diabetic rats compared to controls, and this increase was reversed by both nicergoline and insulin treatments. In all groups studied thromboxane B2 levels were comparable. It is concluded that prostaglandin E2 could mediate the vasodilating action of nicergoline on the placental irrigation and, therefore, improved the hemodynamic state of this organ in diabetic rats.

Female rats rendered diabetics following administration of streptozotocin (40 mg/kg/day I.V.) on the fifth day of pregnancy received daily injections of nicergolin) 200 micrograms/kg/day or 400 micrograms/kg/day I.P.) from day 5 through day 19 of gestation, when animals were sacrificed. It was found that nicergoline significantly reduces the frequency of abortions increases the weight of foetuses and placentas when compared to control diabetic rats. These effects are due neither to a maternal or foetal reduction of glycemia nor to modifications of insulinemia or the levels of sexual hormones of the mother. Histopathological examination of the placentas confirms the positive effect of nicergolin and appears to be due to a direct vascular action.

The electrophysiological diagnosis of peripheral neuropathy in diabetics becomes increasingly difficult with the increase in number of parameters measured. We have examined 102 subjects: 60 diabetics, 32 control subjects and 10 with impaired glucose tolerance. From the 37 recorded parameters during 8 examinations, a linear discriminant analysis allowed us to separate the 19 diabetics with clinical neuropathy and the control subjects with only 5 parameters, with a good concordance (96%): the motor conduction velocities (MCV) of the peroneal and median nerves, the amplitude of the action potential (AP) of the sural nerve, the Hmax/Mmax ratio and the M latency of the Hoffman reflex. These parameters, weighted with a coefficient, constitute a score of discrimination. This score has been tested by the Jackknife method on the same sample (94% of well-classified patients), then validated on the other patients. Thus we propose a method to aid the diagnosis of diabetic peripheral neuropathy, without the arbitrary character of the classical single parameter method, and allowing easy repetition.

Ninety-two young patients of normal weight with glycosuria were classified according to the results of glucose tolerance tests into renal diabetes (32 cases) and chemical diabetes (53 cases). After 5 years or more 17 of the patients with renal diabetes were located. In only one case had the development of chemical diabetes led to correction of the initial diagnosis to that of potential diabetes with a reduced renal glucose threshold. Family histories of diabetes were identical in both groups (renal and chemical diabetes) (35 %) and did not provide any means for distinguishing renal diabetes from diabetes mellitus with a reduced renal glucose threshold. Amongst the 34 subjects with chemical diabetes who were located, 3 had become frank diabetics (9 %). Chemical diabetes persisted in 14 patients (42 %) and 17 (50 %) could be considered to be normal. In addition to the three subjects with frank diabetes, only 9 patients (5 with chemical diabetes and 4 normal) continued to take oral therapy at the time of the final examination. However, 13 of these patients who were not taking any treatment had abandoned it relatively recently. Even if the effectiveness of oral therapy is not fully clear, it should be remembered that continued treatment renders the patient less neglectful as far as diet is concerned. Tests for microangiopathy in the three diabetic patients were negative.

This experiment was conducted to determine the effect of diabetes on uterine prostanoids production in near-term rats. The incidence of an insulin therapy was also studied. On the 21st day of pregnancy, uterine PGE2, PGF2 alpha and PGI2 levels showed a significant increase (respectively p less than 0.05, p less than 0.01 and p less than 0.05) in diabetic rats compared to controls whereas TxA2 production remained unchanged. The insulin therapy restored PGE2 levels, the most potent stimulatory factor of the myometrial fiber at control values, whereas it enhanced significantly PGI2 concentrations (p less than 0.05) and had no effect on PGF2 alpha production; TxA2 levels remaining always unchanged. It is suggested that the increase in uterine protanolds production during diabetes could induce a myometrial hypertonicity and play a role in the disturbances of the fetal development. The maintenance of PGE2 levels to control values by the insulin therapy might contribute to a normal delivery.

The effects of two adrenoceptor antagonists, nicergoline (alpha 1) and acebutolol (beta 1), on the contraction of myometrium in the proestrous rat were compared to those of noradrenaline and phentolamine. The spontaneous myometrial contractions of Wistar rats on the day of proestrus were recorded isometrically and the data were analysed using Wilcoxon non-parametric statistics. All drugs were administered i.v. and the doses are expressed as microgram/kg body weight. Noradrenaline (1200 micrograms/kg per h) induced a 32.5% reduction (P less than 0.001) of the uterine contraction amplitude. Nicergoline did not alter uterine motility significantly when administered alone at doses ranging from 400 to 1600 micrograms/kg. However, successive injections of nicergoline in the same range given during noradrenaline infusion at 600 micrograms/kg per h potentiated the relaxing action of the latter (38%, P less than 0.01). Phentolamine (120 micrograms/kg) reduced myometrial activity by 25% (P less than 0.05). This inhibitory response rose to 65% (P less than 0.001) when the dose of phentolamine was increased to 960 micrograms/kg. When a single injection of nicergoline (400 micrograms/kg) was followed by the administration of increasing doses of acebutolol (120, 1200, 2400 micrograms/kg) the slight inhibitory effect on uterine motility observed after administration of each of the two agents separately became more pronounced (P less than 0.05). It appears from these results that combining noradrenaline with nicergoline and nicergoline with acebutolol leads to potentiation of their relaxing effects. Furthermore the results confirm that nicergoline is a partial alpha-blocker.

Forty-two patients with prolactin-secreting pituitary adenoma (prolactinoma) demonstrated by a radiologically abnormal sella turcica and hyperprolactinaemia were treated with bromocriptine. Baseline serum prolactin levels, which before treatment correlated with the size of the adenoma, returned to normal under bromocriptine in 30 out of 36 cases; in 6 female patients, however, they were lowered but remained moderately high. The dose of bromocriptine and the time required for normalization of prolactinaemia correlated with the size of the tumour. In 11 patients with macroadenoma bromocriptine dosage and prolactinaemia were inversely correlated; in 8 of these the adenoma was reduced in size. In 12 cases where the long-term treatment was interrupted, prolactinaemia rose again, suggesting that the medical treatment alone has no lasting curative effect.

Biological abnormalities, in particular increased T3 and sometimes TSH, are frequently found in thyrotoxic patients treated with radioactive iodine and subsequently enthyroid. A high T3, associated with an increase in FT4 and a low TSH precedes a relapse. An increase in TSH may indicate progression towards hypothyroidism; even if FT4 and T3 levels are within normal limits. Caution must be exercised before affirming that an increased TSH with a high T3 and normal FT4 is indicative of thyroid equilibrium. At all events, the risk of hypothyroidism despite the use of small doses of radioactive iodine is such that the classical limit for the treatment of patients with thyrotoxicosis should be increased beyond the age of 40. In patients with a high TSH despite being clinically euthyroid, the use of thyroid extract in low dosage (50 mg/day) would appear to be desirable in avoiding the subsequent development of hypothyroidism.

A case of carbimazole-induced cholestatic hepatitis is presented. A woman received carbimazole for hyperthyroidism for 3 months. Five months later, she had prompt recurrence of cholestasis parameters after rechallenge (2 days of treatment). Histologic examination showed predominantly centrilobular cholestasis. Only 5 other cases have been published in the literature. An idiosyncratic mechanism seems likely.

A randomised crossover study in eleven diabetic patients with arteritis compared the effects of nicergoline (2,5 mg i.v.) or placebo on haemodynamic and metabolic parameters after exercise tests. Haemodynamic modifications after effort following placebo administration were typical: raised systolic blood pressure, and increased heart rate and myocardial oxygen requirements (systolic BP x heart rate). Modifications after similar effort following nicergoline involved an increase in systolic B.P. only, heart rate and myocardial oxygen requirements remaining unchanged. Blood lactic acid levels after effort and treatment were significantly higher (p. less than 0.01) than after effort without treatment. Overall metabolic and haemodynamic results demonstrate an increase in effort tolerance in diabetic patients with arteritis after nicergoline, this having been previously observed in healthy subjects.

Amongst a group of 27 obese patients subjected to a 10 day fast (250 cal. with 22 Gms protein), 11 picked at random also followed a muscular exercise programme- the others serving as controls. This physical activity was well accepted and tolerated without problems. Weight loss was similar in both groups but the daily nitrogen balance in those patients performing muscular activity was less negative and tended to become positive more rapidly than in the control group. The loss of active muscle mass by protein catabolism as a result of fating was significantly less in the muscular activity group. This may indicate that muscular activity is useful in aiding adaptation to fasting and may orient weight loss preferentially towards fat mass.

During the second semester of 1981, all the diabetic patients who were hospitalized in the department (142 IDD and 75 NIDD) followed an educational program. Approximately half the patients were unable to follow the entire course, owing to visual, motor, intellectual or linguistic impairment. Few patients refused the course (8 cases). Evaluation of the theoretical knowledge at discharge showed poor results in 47% of IDD and 64% of NIDD, with patients in the latter group appearing to be less motivated. Advanced age, unemployment and alcoholism are detrimental factors. In contrast, among 71 IDD who followed only part of the course because of a handicap, 25 nevertheless acquired satisfactory knowledge, justifying an educational program with limited objectives. At follow-up at the outpatient clinic, insulin dependent patients exhibited better metabolic control, self-monitoring and acceptance of their disease; however, the patients who are seen at follow-up examinations are those who have the best theoretical knowledge. A comparative study of hospitalizations shows that admissions for hypoglycemia have decreased between 1978 and 1981, but education is not the only factor. The shortcomings and possible improvements are discussed.

Of a total of 102 cases of male infertility seen over the past ten years, treatment resulted in normalisation of the sperm count in 26, with 12 normal pregnancies resulting. These results concerned cases of oligo-asthenospermia related to a varicocele, pyospermia, hormonal insufficiency or general and psychological disorders. Ten couples were able to have a child with the use of artificial insemination using fresh donor sperm. The abandonment of this technique, nor replaced by the use of frozen sperm provided by a sperm bank, results at the present time in a considerable reduction in the number of inseminations, associated with the overload of these banks. Nevertheless, half of all couples accept the principle of hetero-insemination. The number of couples adopting a child is very low (4% in this study) as a result not only of the difficulties of adoption but also refusal by the couple.

The effects of bilateral ovariectomy on uterine motility and levels of progesterone, oestradiol, cAMP, adrenaline and PGF2 alpha were studied in the rat at midpregnancy. Animals were randomly divided into two groups, at least 15 rats in each, sham-operated serving as controls and ovariectomized. The spontaneous uterine mechanical activity of Wistar rats was recorded isometrically and the electrical activities were recorded simultaneously by two bipolar electrodes. Within 30 minutes of ovariectomy a significant increase of the amplitude of uterine contractions was observed and the simultaneity of electrical activity was significantly improved; these effects became more pronounced at 1h post-ovariectomy (p less than 0.005). Plasma progesterone levels decreased by 20% (p less than 0.01) at 30 min and by 50% (p less than 0.001) 1h after ovariectomy, whereas oestrogen levels remained unchanged. Levels of adrenaline, cAMP and PGF2 alpha in the uterine tissue 1h following ovariectomy were affected as follows: adrenaline (p less than 0.05) and cAMP (p less than 0.001) were reduced and PGF2 alpha augmented (p less than 0.05). It appears that variation of the ratio oestrogens/progesterone induces precociously the activation of uterine mobility and exerts an effect on some factors involved in the regulation of the rat myometrium at midpregnancy.

Within an 8 years' period, 29 insulin-dependent diabetic patients were admitted to hospital on more than 5 occasions, which represents 177 admissions for a total of 3407 days. In almost 70% of the cases loss of control of diabetes was the only reason for admission, and in 33% there was no urgency. Diabetes was unquestionably severe in all patients and truly unstable in 6, but socio-economic reasons accounted for at least one admission in 17 patients and for all admissions in 8. The remaining 64 admissions for uncontrolled diabetes were mostly due to the patients' carelessness. Twelve patients totalling 97 admissions never attended the out-patient clinic. Such carelessness seems to have arisen partly from reactive depression and partly from personality disorders, but the physicians's responsibility cannot be dismissed. In order to reduce the number of unnecessary admissions, diabetologists should provide improved patients' training, pay more attention to their psycho-affective problems and demand regular out-patient attendance.