[Evaluation of an experiment in ophthalmology telemedicine]. / Évaluation d'une expérimentation de télémédecine en ophtalmologie.

PURPOSE: To meet the need for access to eye care in an area with a lack of physicians, a telemedicine workstation in ophthalmology was created. The main objective was to measure the improved access to eye care via telemedicine consultation. METHODS: No criteria of age, sex or geographical location were defined. Depending on the cause for the consultation and the results of the examinations conducted by an ophthalmic technician physically present in the center, the patient might be given a telemedicine consultation with an ophthalmologist. Eleven indicators were defined to achieve the study objectives. Data were compared with a reference eye care center. RESULTS: The quality, safety of care, and medical benefits of telemedicine consultation were not inferior to those of the reference center. The consultations screened 25 cases of age-related macular degeneration, 240 glaucoma, 229 cataracts and 27 diabetic retinopathy. 88.5% of patients were included in a cooperative ophthalmologist/technician protocol, compared with 27.3% in the reference center (P<0.0001). DISCUSSION: The telemedicine workstation must be linked to a main center located at most a one-hour drive away. The equipment must be adapted to the use of telemedicine and to allow the technician to perform the necessary assessments and examinations. The number of emergency department visits after telemedicine consultation at the telemedicine workstation was higher than the reference center, which may lead to a subsequent study. CONCLUSION: Telemedicine consultation improves access to eye care in a medically under-served area.

[The French glaucoma and ocular hypertension 1-day study]. / Enquête Française Glaucome et Hypertonie 1 Jour.

PURPOSE: The purpose of this study was to describe the distribution and characteristics (age, duration, type, treatment, etc.) of ocular hypertension and glaucoma in French ophthalmologic practices. METHODS: The French glaucoma and ocular hypertension 1-day study is a descriptive cross-sectional "1-day" type survey, conducted among all ophthalmologists of mainland France. They had to include all patients aged 18 years and over with ocular hypertension or glaucoma who were seen on November 25th 2003. The participation rate was 24.0% (1.173 ophthalmologists). Among the 3.919 patients included, 3.896 subjects (99%) had usable data for the statistical analyses. RESULTS: The ophthalmologists reported treating 16 patients with ocular hypertension or glaucoma on average per week. Among the patients, 29.5% had ocular hypertension, 61.7% had open-angle glaucoma, 3.4% had normal tension glaucoma, and 5.5% angle-closure glaucoma. The ophthalmologists used surgery or laser treatment for 74.1% of angle-closure glaucoma, while for other pathologies, treatment with drugs only was preponderant. More than 87% of patients received one or several ocular treatments: beta-blockers (59.3%), prostaglandins (50.1%), carbonic anhydrase inhibitors (21.6%), or mydriatic sympathomimetics (6.3%). CONCLUSIONS: The characteristics of glaucoma and ocular hypertension (type of glaucoma, age, duration, etc.) correspond to those of other Western populations. The therapeutic habits of French ophthalmologists is in line with current international guidelines.

[Efficacy of first- or second-line latanoprost on intraocular pressure and ocular symptoms in patients with open-angle glaucoma or ocular hypertension]. / Efficacité du latanoprost, donné en première ou deuxième intention, sur la pression intra-oculaire et la symptomatologie oculaire chez des patients présentant un glaucome à angle ouvert ou une hypertension oculaire simple.

OBJECTIVES: The aim of this study was to assess the changes in intraocular pressure (IOP) and ophthalmic symptoms with the Glaucoma Symptom Scale in patients suffering from open-angle glaucoma (OAG) or ocular hypertension (OHT) after 3 months of treatment with latanoprost. MATERIALS AND METHODS: This multicentric open study was carried out in adult patients suffering from OAG or simple OHT (naive or previously treated with monotherapy) and needing a change or initiation of anti-glaucomatous treatment. One drop of latanoprost 0.005% was instilled every evening for 12 weeks in each affected eye. Efficacy was assessed by the variation in IOP and ophthalmic symptomatology at the end of treatment. Prognosis factors associated with a relative IOP reduction of at least 30% were sought (using a logistic regression model). RESULTS: A total of 920 patients suffering from OAG (54%) or OHT (44%), either previously treated (69%) or naive (31%), were included. The male:female ratio was 0.78 and the mean age was 63+/-13 years. At inclusion, the mean IOP was 22.1+/-3.8 mmHg. After treatment, IOP was significantly decreased by 5.1+/-4 mmHg, corresponding to a 22% reduction. IOP reduction was 7.1+/-4 mmHg, corresponding to 29% in naive patients and 4.2+/-4 mmHg, corresponding to 19% in previously treated patients. A relative IOP reduction of at least 30% was reached by 47% of naive patients and 21% of previously treated patients. In previously treated patients, a relative IOP reduction of at least 30% had a greater chance of being reached in men with previous ophthalmic history and high IOP at inclusion (above 21 mmHg). IOP reduction was similar in patients with OAG and OHT. A significant improvement in ophthalmic symptoms was observed after treatment in previously treated patients. A total of 7% of the patients presented an adverse event affecting the visual system: eye irritation (2%), eye pain (2%), or eye hyperemia (1%). Compliance was good for 94% of the patients. CONCLUSION: Latanoprost given as first or second-line treatment at the recommended dose effectively decreases IOP in patients with OAG or OHT. This treatment also improves visual and nonvisual symptoms in previously treated patients and presents a good safety profile.

Zinc deficiency in elderly patients.

Zinc is needed for growth and development, DNA synthesis, neurosensory functions, and cell-mediated immunity. Although zinc intake is reduced in elderly people, its deficiency and effects on cell-mediated immunity of the elderly have not been established. Subjects enrolled in "A Model Health Promotion and Intervention Program for Urban Middle Aged and Elderly Americans" were assessed for nutrition and zinc status. One hundred eighty healthy subjects were randomly selected for the study. Their mean dietary zinc intake was 9.06 mg/day, whereas the recommended dietary allowance is 15 mg/day. Plasma zinc was normal, but zinc in granulocytes and lymphocytes were decreased compared with younger control subjects. Of 118 elderly subjects in whom zinc levels in both granulocytes and lymphocytes were available, 36 had deficient levels. Plasma copper was increased, and interleukin 1 (IL-1) production was significantly decreased. Reduced response to the skin-test antigen panel and decreased taste acuity were observed. Thirteen elderly zinc-deficient subjects were supplemented with zinc, and various variables were assessed before and after zinc supplementation. Zinc supplementation corrected zinc deficiency and normalized plasma copper levels. Serum thymulin activity, IL-1 production, and lymphocyte ecto-5'-nucleotidase increased significantly after supplementation. Improvement in response to skin-test antigens and taste acuity was observed after zinc supplementation. A mild zinc deficiency appears to be a significant clinical problem in free-living elderly people.

Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases.

The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.

[Some factors influencing the bioavailability of zinc in oral pharmaceutical dosage forms]. / Etude de quelques facteurs influençant la biodisponibilité du zinc dans les formes pharmaceutiques à usage oral.

Absorption and distribution of zinc in 6 dosage forms were determined in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a dose corresponding to 45 mg elemental zinc. The aim of this study was to document the influence on zinc bioavailability of factors such as the chemical form of zinc, the pharmaceutical form, and the division of the administered dose. The pharmacokinetic parameters indicate for gelatin capsules without excipients taken in a non divided dose better performances for zinc gluconate in comparison to zinc sulfate. Concerning the pharmaceutical form, little difference is observed between an aqueous solution and a gelatin capsule for zinc sulfate and a non divided dose; on the contrary, a commercial gelatin capsule containing zinc gluconate with various excipients show better performances than gastro-resistant tablets when zinc intake is 3 times 15 mg. Finally, the division in 3 parts of the dose of zinc sulfate given in gelatin capsules very significantly improves zinc absorption. These results demonstrate the interest of the developed pharmacokinetic method in the assessment of zinc bioavailability in different pharmaceutical dosage forms.

Absorption and metabolism of oral zinc gluconate in humans in fasting state, during, and after a meal.

The absorption and metabolism of zinc in a commercial form for oral use (Rubozinc, 15 mg zinc as gluconate) were investigated in 10 subjects by a kinetic study of the serum zinc profile after administration of 45 mg zinc under three conditions: after an overnight fast, during a standardized breakfast, and 2 h after this meal. The pharmacokinetic parameters were calculated by a method suitable to the characterization of rebound effects (recycling of the element in the gastrointestinal tract). In fasting state, the parameters were comparable to those previously collected in the same subjects with oral 45 mg zinc as sulfate, except with very significantly higher Cmax and area under curve (AUC), showing a better bioavailability for zinc in the commercial form. The light meal perturbed the absorption process as evidenced by the significant increases in the lag time (+180%), the tmax (+57%), and the lag times for the first two cycles during the meal. However, the parameters returned to normal values 2 h after the meal. The Cmax only moderately decreased during the meal (31%) as did the AUC (-28%). An important delay in the absorption of zinc in the commercial form when taken during a meal was therefore demonstrated, but the effect on zinc bioavailability was only moderate.

Peptidylglycine alpha-amidating monooxygenase activity and TRH and CRF biosynthesis. Role of copper.

Carboxy-terminal amidation of biologically active peptides, an important characteristic of more than half of these substances, occurs during the maturation process of peptide precursors. It is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM), an enzyme that is copper-dependent. We show here that alterations of copper stores in cultured cells from different origins (pancreas and hypothalamus) affect the immunoreactivity of thyrotropin-releasing hormone (TRH) and corticotropin-releasing factor (CRF) (two alpha-amidated peptides). This suggests that copper can affect neuropeptide biosynthesis and may play a role in the endocrine or central nervous system function.

Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation.

Starting from the experimental design of the established 'Zinc Tolerance Tests', the absorption and distribution of the essential trace element zinc in humans was investigated in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a pharmacological dose of the metal, i.e. 0.69 mmol (45 mg) zinc as ZnSO4.7 H2O. The adopted experimental conditions include frequent measurements of serum concentrations, a total investigation time of 8 h after ingestion, and a correction of basal zinc levels taking into account the circadian variation. Rebound effects were evidenced in the time versus concentration curves showing a regular recycling of the element in the digestive tract. Estimation of the parameters by an original method allowed us to calculate the characteristics of the cycles. The first one occurred after 1.4 h, before the time needed for appearance of the maximum concentration which was around 2.3 h, and exhibited mean reabsorption of 70% of administered dose. The subsequent ones, maximum 5 during the investigation period, appeared at regular intervals of approximately 1.2 h, with a decrease in the quantity reabsorbed. These observations are consistent with the previously reported endogenous secretion of zinc, a physiological mechanism contributing to zinc homeostasis.

The role of the sodium pump in the plasma membrane potential changes during mast cell activation.

The role of the sodium pump in the plasma membrane potential changes induced by compound 48/80 and by antigenic challenge has been investigated using a fluorescent potential sensitive probe, bis-oxonol. Compound 48/80 induced a fast decrease of the fluorescence of bis-oxonol followed by a delayed decrease. The antigenic stimulation induced only a delayed decrease of fluorescence. Zinc gluconate inhibited the first decrease but did not alter the second one. The delayed decrease was inhibited by ouabain or by the absence of potassium. These results suggest that compound 48/80 induced mast cell secretion via a zinc-sensitive mechanism followed by activation of the sodium pump. The changes in the plasma membrane potential during the antigenic stimulation are due to the activation of the sodium pump but occur after the secretion process.

Effects of chronic prednisolone administration on plasma copper in rats with adjuvant arthritis.

Copper metabolism is known to be significantly affected by inflammation or by glucocorticoid administration. We have previously demonstrated that acute prednisolone administration induces a moderate but sustained increase in plasma copper in healthy rats while it induces a more pronounced but shorter increase in rats with adjuvant arthritis. In the present study we have investigated the effects of chronic prednisolone administration (around 0.65 mg/kg daily in food) in both healthy rats and rats with adjuvant arthritis at various stages of the disease. In healthy rats, a slight but significant increase of 11% was observed in plasma copper after 3 weeks of treatment. This modification was no longer apparent after 5 weeks of treatment. In arthritic rats, plasma copper was, as expected, higher than in healthy rats and reached a maximum 3 weeks after adjuvant injection. In prednisolone-treated arthritic rats, there was a sustained decrease in plasma copper starting after 2 weeks of treatment which could be correlated with an improvement of the clinical and biochemical signs of inflammation. In conclusion, chronic prednisolone treatment only slightly increases plasma copper in healthy rats while in arthritic rats plasma copper is dependent on the severity of the disease which is improved by the treatment.

Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP).

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.

The sensitivity to Zn2+ discriminates between typical and atypical mast cells.

The effects of zinc gluconate have been studied on rat peritoneal mast cells and rat basophilic leukemia cells (RBL 2H3) stimulated by various secretagogues. The IC50's of zinc gluconate on peritoneal cells were (microM): 1.6, 1.9, 5.4 and 18 for ionophore A23187, phorbol 12-myristate 13-acetate, substance P and immunoglobulin E-antigen, respectively. Higher concentrations of zinc gluconate were required to inhibit histamine secretion from RBL 2H3 cells, i.e. 12 microM (ionophore A23187) and 140 microM (immunoglobulin E-antigen). Zinc gluconate (10(-4) to 10(-3) M) also inhibited the IgE-dependent contraction of guinea pig trachea but was unable to affect that induced by exogenous histamine. These results suggest that zinc gluconate acts intracellularly and is selective of "typical" or "connective tissue" mast cells.

Ontogenetic expression of peptidyl-glycine alpha-amidating monooxygenase mRNA in the rat pancreas.

Qualitative and quantitative expression of m.RNA coding for Peptidyl-Glycine alpha-Amidating Monooxygenase (PAM) in the developing rat pancreas was investigated by Northern and dot blot hybridization, with a bovine PAM c.DNA probe (0.7 kb fragment). A specific hybridization signal was evidenced for a 3.7 kb m.RNA species. Measurement of PAM m. RNA rate during the rat pancreas ontogenesis revealed a biphasic profile which appeared corelated with that of gastrin and TRH m.RNA respectively. On the other hand, streptozotocin-treatment resulted in a 50% decrease of PAM m.RNA levels.

Comparison of effects of chronic inflammation and long-term prednisolone administration on zinc metabolism in rats.

It is well known that plasma zinc is depressed in animals following administration of endotoxin, endogenous pyrogen, interleukin-1, and glucocorticoids. The modification is related to an induction of liver metallothionein causing an accumulation of the element in this organ. The changes in zinc metabolism induced by adjuvant arthritis in rats evidenced a redistribution of body zinc with a rapid and sustained decrease in plasma zinc that occurred simultaneously with an increase in liver zinc levels, and slower modification in erythrocyte and femur zinc concentrations. These effects were compared to those induced by a long-term corticosteroid administration in healthy rats. Male Wistar rats received either a commercially available complete maintenance diet or the same diet enriched with prednisolone at a level providing 1 mg prednisolone/kg body weight. Groups of animals were sacrificed after 3 or 5 weeks' treatment. Ingested food quantity, total body weight, total serum proteins and serum albumin were similar in treated and control rats. No significant modifications in parameters of zinc status could be observed after 3 weeks of treatment. However after 5 weeks, plasma zinc was significantly lower in treated rats as compared to controls, but modifications in liver, erythrocyte and femur zinc did not reach statistical significance. Changes induced by long-term corticosteroid administration are therefore less intense than those due to the inflammatory process of adjuvant arthritis.