A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion.

AIM: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety. METHODS: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia. RESULTS: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. - 0.1 kg, p = 0.013), quality of life better with CIPII. CONCLUSIONS: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.

Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates.

Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole. We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-scoreor=6 courses) and a marked antiestrogenic response--defined by a level of 17beta-estradiol50% between baseline and 1 year--were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9-57.2] (p=0.007) and 5.7 [1.3-25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine -3.3+/-0.5% [-4.3 to -2.3], p<0.0001 and at the hip -2.9+/-0.6% [-4.1 to -1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1+/-0.9% [2.3 to 5.9], p=0.008), and BTM decreased (-24%, -39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group). Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17beta-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.

[Complementary methodological steps in the analysis of rhythms: search of periods, modelling. Examples of plasma melatonin and temperature curves]. / Eléments méthodologiques complémentaires dans l'analyse des rythmes: recherche de périodes, modélisation. Exemples de la Mélatonine plasmatique et de courbes de températures.

The choice of the period is a problematic in the field of the analysis of rhythms which is not yet sufficiently formalized in the sense that it was often postulated that the period is known and more precisely in the case of the circadian rhythms. We propose some methods which have a great reliability in the determination of the period and consequently can allow to characterize the parameters of the rhythmic phenomena (amplitude, phase, rhythmic level) with more precision. Traditional "cosine" modeling is always an unquestionable interest in the sense that it is a good reflect of the behavior of a biological periodic phenomenon in the course of time. However its employment requires to check complementary assumptions of validity in front of a statistical expertise. We will show the main ones. On the other hand it seems that this model requires a certain adaptation as it shows for example in the variabilities of the phase that one can notice in the behaviour of the biological rhythmic phenomena.

Reduced joint pain after short-term duodenal administration of seal oil in patients with inflammatory bowel disease: comparison with soy oil.

BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).

High dose proton pump inhibitor response as an initial strategy for a clinical diagnosis of gastro-oesophageal reflux disease (GERD). Swedish multi-centre group in primary health care.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) in primary care rests primarily on symptoms. Oesophageal acid exposure is the most important pathogenic factor and it is likely that symptom response to acid inhibition also identifies patients with GERD. OBJECTIVE: The aim of this study was to evaluate the outcome of a symptom-based strategy in the management of GERD patients in primary care. METHODS: Patients in general practice with main symptoms of at least moderate heartburn or regurgitation were given omeprazole 20 mg b.i.d. openly for 7 days (first phase). Responders with later relapse were randomized to double-blind treatment with omeprazole 20 mg o.m. or placebo for 2 weeks (second phase). A response in both phases was defined as a decrease by at least three grades on a seven-grade Likert scale and no more than mild intensity of the main symptom. RESULTS: Of the 362/371 recruited patients who were evaluated in the first phase, 73% were responders. A total of 174/179 patients with a relapse were assessed in the second phase, and 74 and 28% in the omeprazole and placebo group, respectively, were defined as responders (P: < 0.001, 95% confidence interval 33-59). CONCLUSIONS: GERD patients are highly responsive to omeprazole 20 mg b.i.d. They are equally responsive to omeprazole 20 mg o.m. at symptomatic relapse, but have a low response rate to placebo. Omeprazole is a valuable therapeutic instrument to detect and treat patients with GERD in general practice.

[Endometrial thermocoagulation via balloon: technique, mechanism of action, and evaluation]. / Thermocoagulation endométriale par ballonnet: technique, mécanisme d'action et évaluation.

Thermal balloon endometrial ablation is indicated for women suffering from menorrhagia. This easy technique can be performed safely, without using operative hysteroscopy. The rate of minor complications is low (< 4%). Thermotherapy treats the endometrium and superficial myometrium tissues without risk of injury to the bladder and bowels. The success rate of this operation is 90% in selected patients of studies published between 1996 and 1998, with a follow-up period of 12-24 months. However, long-term randomized controlled studies are needed to compare thermotherapy and other endometrial ablation procedures.

[Syphilis in Europe in antiquity: the fetus of Costebelle and other new gifts from osteoarchaeology]. / La syphilis en Europe dans l'Antiquité: le foetus de Costebelle et les autres nouvelles données ostéoarcheologiques.

Tomb Nr 1 of the ancient cemetery of Costebelle, attributed to the 4th century AD, contained the skeleton of a pregnant female and that of her foetus in the pelvic cavity. This was aged seven months, was almost complete and showed an exceptional example of bony lesions suggestive of infection. Its etiology suggested the likelihood of early congenital syphilis. This case raises the question of the theory of the importation of venereal disease into Europe, about a 1000 years later, by the crews of Christopher Columbus. The foetus of Costebelle is not an isolated example : other osteo-archaeological findings make a case for the existence of a treponeme (venereal or non venereal) in Europe before 1493.

Effects of zinc supplementation on blood rheology during exercise.

We previously reported a higher blood viscosity at corrected hematocrit (45%) (explained by a higher value of erythrocyte rigidity) in football players with low serum zinc (Zn) and thus presumably Zn deficiency; subjects with low serum zinc had also an impairment in performance. This interventional study was undertaken in order to assess the effects of zinc supplementation (compared to placebo) on blood rheology and performance either at rest or during exercise. Ten male healthy volunteers (age: 26+/-1.3 yr; weight 67.9+/-2.24 kg; height 177+/-3 cm) received at random order either zinc (20 mg/day) and placebo, according to a double blind cross-over procedure, during seven days. In each case on the eighth day they performed a 25 min submaximal exercise-test. At rest blood viscosity at corrected hematocrit 45% (gamma = 1000 s(-1)) was lower after Zn (3.56+/-0.14 vs. 4.13+/-0.16 mPa.s, p = 0.009), explained by a lower RBC rigidity index 'k' according to Quemada's equation (1.65+/-0.07 vs. 1.84+/-0.08, p = 0.03). Hematocrit and plasma viscosity were unchanged, but RBC aggregation was decreased (laser retrodiffusion-derived aggregation time 'Ta' 3.52+/-0.51 vs. 2.75+/-0.59, p = 0.02). The increase in blood viscosity during exercise is lower after Zn than placebo. Blood viscosity at corrected hematocrit 45% remains unchanged during exercise after Zn, yet it increases after placebo. RBC rigidity index 'k' remains lower during exercise after Zn. The rating of perceived exertion (Borg's scale) at the 20th minute of exercise is lower after zinc (5.6+/-0.4 vs. 6.6+/-0.4, p = 0.008). This study confirms that Zn improves erythrocyte deformability, decreases the exercise-induced acute increase in blood viscosity, and improves exercise tolerance. Since Zn deficiencies are not unfrequent in sportsmen, these findings may be potentially relevant to sports nutrition.

[Dermoid cyst of the ovary. False positive diagnosis in iodine 131 scintigraphy of differentiated thyroid cancers]. / Kyste dermoïde de l'ovaire. Faux positif à reconnaître lors de la surveillance scintigraphique à l'iode 131 des cancers différenciés thyroïdiens.

BACKGROUND: Total body 131-iodine labeled scintiscan is used to screen for residual tumoral tissue after ablation of differentiated thyroid carcinoma. At therapeutic doses, radioactive iodine can also be used for treatment. Thyroglobulin level, usually undetectable a few months after total thyroidectomy and metabolic irradiation with 131-iodine in patients without initial metastases, is absolutely necessary for interpreting the scintiscans. Iodine uptake occur in dermoid cysts which usually contain thyroid tissue. CASE REPORT: A 44-year old woman underwent total thyroidectomy with node dissection for papillary carcinoma of the thyroid with a vesicular architecture. Four months later, the total body 131-iodine scintiscan demonstrated a round zone of uptake in the pelvic area. The lesion was found to be a typical dermoid cyst. No thyroid or tumoral tissue could be demonstrated. DISCUSSION: Dermoid cysts can be the cause of false positive 131-scintiscans in patients followed after resection of differentiated thyroid carcinoma. Unlike previously reported cases, the dermoid cyst in this patient was totally devoid of thyroid tissue.

Effects of zamic as a means for zinc supplementation in growing children.

We investigated the effects of zinc supplementation in case of moderate growth retardation in which GH treatment could not be used. Zamic (ZA, an association containing arginine, L-methionine, and zinc; from Aguettant pharmaceuticals) was compared with arginine aspartate (AA) (5 g) in a crossover randomized trial (6 mo of each treatment at random order over 1 yr). We present preliminary results of 24 children who completed the study (3 girls, 21 boys, age 9-13 yr). Subjects had to be prepubertal, with no GH deficiency diagnosed. In 15 subjects growth velocity was lower than 5 mm/mo: In this case ZA improved growth velocity (rising from 3.105 +/- 0.229 to 5.4 +/- 0.69 mm/mo p < 0.01), whereas the effect of AA was not significant. The increase in growth velocity was higher with ZA (+2.44 +/- 0.657 mm/mo) than AA (+0.438 +/- 0.450 mm/mo) p < 0.05. These results suggest that ZA is more efficient than AA, consistent with the hypothesis that zinc needs are increased in those children in this period of life.

Effects of calprotectin in avridine-induced arthritis.

Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.

Results of ultrasonically guided percutaneous ethanol injection into parathyroid adenomas in primary hyperparathyroidism.

Surgery is the usual treatment for primary hyperparathyroidism. However, some patients with high surgical risks are not suitable for surgery. For such patients, we propose, as an alternative treatment, ultrasonically guided percutaneous ethanol injection into parathyroid adenomas, in order to induce necrosis of the tumor. We report, here, the results of ultrasonically guided percutaneous ethanol injection into parathyroid adenomas, during a prolonged follow-up period up to 49 months, in a group of 13 patients (median age 79 years) with primary hyperparathyroidism and contraindications for surgery. In seven patients, complete normalization of plasma calcium, phosphorus and parathyroid hormone (PTH) levels was achieved after ethanol injections, with no recurrence of hypercalcemia during a median follow-up period of 28 months (total success). In these seven patients, plasma calcium, phosphorus and PTH levels were normalized 48 h after the successful ethanol injection. In four patients, a partial success was obtained with clinical improvement and normalization of plasma calcium levels but without complete normalization of plasma PTH levels. This partial success is due to incomplete necrosis of the adenoma, as has been confirmed in one patient by histopathological examination. The ethanol injection treatment failed in only two patients. This treatment was always well tolerated and no major side-effects were observed. In conclusion, our results give evidence that ultrasonically guided percutaneous ethanol injection into parathyroid adenomas can be a very useful alternative therapy in patients not suitable for surgery.

Vitamin D3 and calcium to prevent hip fractures in elderly women.

BACKGROUND: Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS: We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS: Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS: Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection.

The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished was investigated after the i.v. infusion--once during the night and once during the day. The clearance of melatonin from blood showed a biexponential decay. The pharmacokinetic parameters in the two studies were similar, except for the disappearance rate constant beta and the apparent volume of distribution at steady-state (Vss). Supplementary peaks or troughs were superimposed on the plateau and the falling part of the profile. They were not due to stimulation of endogenous secretion, because they were also seen in the pinealomectomized patient. During the melatonin infusion, the plasma hormone level reached a steady-state after 60 and 120 min, and when it was equal to the nocturnal level. The infusion regime may be valuable in replacing blunted hormonal secretion in disease states.

The effects of melatonin and pinealectomy upon local cerebral glucose utilization in awake unrestrained rats are restricted to a few specific regions.

The effects of the infusion of melatonin (MT) and/or of pinealectomy upon glucose utilization in anatomically discrete regions of the brain of freely moving rats have been studied by the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose technique. The experiments were made from 14.00 to 16.00 h, when MT is normally not secreted by the pineal gland, in order to compare the local cerebral glucose utilization (LCGU) response to MT from animals with long-term (pinealectomized) or short-term (pineal intact) absence of MT secretion. The majority of the 98 brain areas examined showed no change in LCGU after MT administration and/or pinealectomy. Pinealectomy increased the LCGU in the median mammillary nucleus only, whereas following MT administration, an increase in LCGU was observed in 3 cerebral regions of intact rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexus of the third ventricle) and in 5 cerebral regions of pinealectomized rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexuses of the lateral ventricles, third and fourth ventricles). Except for the choroid plexuses of the fourth ventricle, there was no difference in LCGU response to MT between pinealectomized and intact animals. This does not favor the hypothesis of receptor supersensitivity under the conditions of this experiment. Our results suggest that the hypothalamus, nucleus of the solitary tract and choroid plexuses represent a neural substrate through which MT could influence the activity of the central nervous system when administered at a low dose under near-physiological conditions.

Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans.

An oral preparation of melatonin was administered daily at 22.00 h to 6 healthy volunteers during summer on 4 consecutive days (days 1-4). The daily dose was 8 mg of melatonin as a single. Three 24-h melatonin, cortisol and prolactin profiles were determined in plasma by radioimmunological methods: 1) before treatment (day 0); 2) the first day after the 4-day treatment had been stopped (day 5), 3) the third day after withdrawal of this treatment (day 7). For the melatonin rhythm, an advanced phase was observed at day 7 vs day 0, whereas the amplitude and the mesor were not modified, whatever the day. For the prolactin profile, a significant increase as compared with the control day (day 0) was detected only at day 7 between 19.00 and 21.00 h. No modification was recorded for the plasma cortisol secretion. These results suggest that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion. This effect must be investigated over several days after the treatment has ended.

[Surgical pulmonary biopsy under local anesthesia and its results (based on 93 cases)]. / La biopsie pulmonaire chirurgicale sous anesthésie locale et ses résultats (d'après 93 cas)

The authors report 93 observations during which OCB were performed under local anesthesia. They insist on the validity of the method which can be used on fragile patients or on those with respiratory insufficiency for whom an exploring thoracotomy would be contra-indicated. Incidents were minor and momentary (pneumothorax, pleural reaction). It is mostly in diffuse lesions of miliary and fibrotic nature that this technique was used to identify various lesions : silicosis, sarcoidosis, tuberculosis, histiocytosis, etc... In a third of the cases, lesions were not specific and could not be definitely identified in parieto-alveolar fibrosis or inflammatory alveolitis.