Kalil Mondadori e Flavia Placeres a serviço da Naturologia / Kalil Mondadori and Flavia Placeres at the service of Naturology

Em entrevista realizada por Isadora F. B. O. Alves, em 01 e 02 de junho de 2014, Kalil Mondadori, na função de Presidente da Associação Brasileira de Naturologia ­ ABRANA ­ e Flavia Placeres, Presidente da Associação Paulista de Naturologia ­ APANAT ­ fazem revelações importantes para a construção da história da inserção da Naturologia no universo das práticas trabalhistas voltadas para a saúde.(AU)

Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes.

AIMS: To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy. RESEARCH DESIGN AND METHODS: Ninety-seven patients were randomized in a multicentre, open-label, 32-week crossover study. Primary variables evaluated: haemoglobin A1c (A1c), 2-h post-prandial blood glucose (BG), hypoglycaemia rate (episodes/patient/30 days), incidence (% patients experiencing > or = 1 episode) of overall and nocturnal hypoglycaemia. RESULTS: At endpoint, A1c was lower with the insulin lispro mixture plus metformin compared with glargine plus metformin (7.54% +/- 0.87% vs. 8.14% +/- 1.03%, P < 0.001). Change in A1c from baseline to endpoint was greater with the insulin lispro mixture plus metformin (-1.00% vs. -0.42%; P < 0.001). Two-hour post-prandial BG was lower after morning, midday, and evening meals (P < 0.001) during treatment with the insulin lispro mixture plus metformin. The fasting BG values were lower with glargine plus metformin (P = 0.007). Despite lower BG at 03.00 hours (P < 0.01), patients treated with the insulin lispro mixture plus metformin had a lower rate of nocturnal hypoglycaemia (0.14 +/- 0.49 vs. 0.34 +/- 0.85 episodes/patient/30 days; P = 0.002), although the overall hypoglycaemia rate was not different between treatments (0.61 +/- 1.41 vs. 0.44 +/- 1.07 episodes/patient/30 days; P = 0.477). CONCLUSION: In patients with Type 2 diabetes and inadequate glucose control while on insulin or insulin and oral agent(s) combination therapy, treatment with a twice-daily insulin lispro mixture plus metformin, which targets both post-prandial and pre-meal BG, provided clinically significant improvements in A1c, significantly reduced post-prandial BG after each meal, and reduced nocturnal hypoglycaemia as compared with once-daily glargine plus metformin, a treatment that targets fasting BG.

Efficacy of Humalog injections before an afternoon meal and their acceptance by children and adolescents with type 1 diabetes.

AIMS: To evaluate the acceptability and efficacy of an injection of insulin lispro, before an afternoon meal. METHODS: The subjects, 43 patients with Type 1 diabetes, 16 boys and 27 girls, aged 12.4 +/- 2.4 years, were randomly assigned to the treatment (n = 20) or the untreated control group (n = 23). The treatment was an injection of insulin lispro immediately before the afternoon meal. The control group had no injection. The treatment and the control group consumed identical types of meals for 2 months. The mean before-dinner blood glucose was measured during the last 2 weeks of the study. RESULTS: Injection of insulin lispro resulted in a significant reduction in the before-dinner blood glucose compared with the untreated control group (10.4 +/- 3.8 mmol/l vs. 14.7 +/- 3.9 mmol/l, respectively). The number of days on which the blood glucose was > 10 mmol/l was reduced by half in the insulin lispro group. The difference in HbA1c between baseline and endpoint differed slightly but significantly between the two groups, in boys. Treated patients ate the meal less frequently (11.4 +/- 3.0 times per 15 days) than the control patients (14.4 +/- 0.6 times per 15 days) and injected themselves with insulin 8.9 +/- 3.6 times per 15 days. The HbA1c increased significantly with the number of meals taken without injection. There was no statistically significant difference in the frequency of hypoglycaemia or changes in weight between the two groups. CONCLUSIONS: We conclude that an injection of insulin lispro before the afternoon meal can effectively lower the before-dinner blood glucose, and in boys also lowers the HbA1c. Patients were satisfied with the lower blood glucose before dinner, and did not find the insulin lispro injection difficult. However, compliance with the protocol procedures decreased during a subsequent 6-month period.

Which are the insulin treatment regimens used in France? The "Schema survey".

OBJECTIVE: To examine how insulin therapy is used in France under real life conditions for type 1 and insulin-treated type 2 patients. MATERIAL AND METHODS: The "Schema survey" was a cross-sectional survey carried out for all the insulin-treated patients seen by participating physicians on a given day. All registered diabetologists in France were invited to participate, 934 initially agreed, 450 returned at least one questionnaire. These 450 physicians appeared to be representative of the whole. The reasons for which 484 physicians who had initially agreed to participate did not were collected by telephone and do not seem to introduce a bias. 1,263 patients were included in the analysis, type 1: 57.6%, type 2: 36.8%. RESULTS: Over 54% of type 1 patients were treated with 3 or more insulin injections per day. Among type 1 patients treated with 2 injections per day, 30% were younger than 18. Over 82% type 2 patients were treated with 1 or 2 insulin injections per day. A regimen combining oral agents and bed time NPH was used in 18% of type 2 patients. Premixed insulins were used by 45.5% of type 2 and 39.5% of type 1 patients. For patients under 3 or more injections per day, over 30 different regimens were identified. About 40% of patients, either type 1 or 2, were poorly controlled (HbA1c > 8.5%). The frequency of blood glucose monitoring appears to comply with recommendations. CONCLUSIONS: Under real life conditions, a majority of French type 1 patients are treated with intensified multiple injections but a lot are not, despite inadequate metabolic control. Only few type 2 patients are treated with intensified therapy.

[Frequency and costs of hospital stays for hypoglycemia in France in 1995]. / Fréquence et coûts des séjours hospitaliers pour hypoglycémie en France en 1995.

OBJECTIVES: Diabetes is a highly prevalent chronic disease causing serious complications. Hypoglycemia is the most frequent, the most serious, and the most feared by patients and families. Hospitalization may be necessary and can be costly. The main objective of this study was to determine the number of cases of hypoglycemia cared for annually in France in an inpatient setting and to estimate the annual financial impact of hospitalizations. PATIENTS AND METHODS: The number of hypoglycemias seen annually by physician s in France and the frequencies of hospitalizations for hypoglycemia were determined from a literature search. Complementary data on costs were obtained from the national PMSI mission. Our sample included 817 hospital stays between 1994 and 1995. RESULTS: In 1992, physicians in France cared for 40,000 episodes of hypoglycemia. There were 10,800 hospitalizations. In 9 out of 10 cases, the hospital stay lasted several days and, despite hospitalization, 1.9% of the patients died. Mean total medical cost of a hospital stay for hypoglycemia was 14,000 FF ($2,100) (median 10,000 FF, range 1,200-120,000 FF). Mean length of stay was 6.6 days. DISCUSSION: Mean unit cost for hospital stays for hypoglycemia is high. Based on the 1993 SESI survey, the probable annual cost for the society for hospital care of patients with hypoglycemia was an estimated 108 to 151 million FF ($16-22 million) in 1995. This figure only takes into account the visible cost of caring for hypoglycemia patients. Ambulatory care was not taken into consideration. Education, for the patient and family, is fundamental for the prevention and treatment of hypoglycemia. CONCLUSION: It is important to have this estimation due to the absence of a medicoeconomic study on ambulatory and hospital care for hypoglycemia. Complementary studies should be conducted to estimate the total annual cost of hypoglycemia in France.

[Results of international clinical trials with raloxifene]. / Résultats des études cliniques internationales du raloxifène.

A new drug class called Selective Estrogen Receptor Modulators (SERM) could combine ideal properties for a product designed for menopausal women. The most widely studied member of this class is raloxifene which is currently marketed in several countries for the prevention of osteoporosis in menopaused women. This product is a nonsteroidal derivative of benzothiophene which, like estrogens, has a preventive effect against bone loss involving the spine and peripheral skeleton and a cholesterol lowering effect, both in the ovariectomized rat and in menopausal women. Unlike estrogens, raloxifene does not stimulate breast or uterine tissue. These interesting properties make raloxifene a possible preventive treatment for osteoporosis and other menopause-related risks for menopausal women of all ages. Multicenter studies have been conducted in recently menopausal women who received either raloxifene at the doses of 30, 60, or 150 mg/day or a placebo in a randomized protocol. All subjects were also given calcium supplementation. Bone density was measured twice a year for 36 months by dual X-rays absorptiometry and showed a significant decrease at all sites in the placebo group while there was a significant increase in the spine, the hip and the overall skeleton for all three raloxifen groups. After 24 months of treatment, mean increase over placebo was 2.4% for 60 mg raloxifene measured on the spine and total hip and 2% for the overall skeleton. Markers of bone formation (serum osteocalcin and bone alkaline phasphatase) and resorption (urinary CrossLaps) decreased significantly reaching, after 3 to 6 months of treatment, the levels observed in non menopausal women. In addition, total serum cholesterol as well as LDL-cholesterol decreased significantly in a dose-dependent fashion in all groups treated with raloxifene. Serum HDL-cholesterol and triglycerides did not very significantly during treatment. Hot flashes were the most frequently observed undesirable effect, at a frequency slightly higher in the raloxifene group (25%) than in the placebo group (18%). This undesirable effect was of low intensity and generally occurred during the first months of treatment. It did not cause a higher drop out rate (raloxifen 1.5%; placebo 2.1%). The preliminary data at two years follow-up suggest that raloxifene is not associated with an increased risk of breast cancer. In conclusion, raloxifene is a particularly interesting drug for menopausal women showing very promising efficacy and clinical tolerance.

Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps.

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

[The medical treatment of condylomatosis of the lower genital tract. A multicenter outpatient study]. / Trattamento medico della condilomatosi del basso tratto genitale. Studio policentrico ambulatoriale.

Beta-interferone (Frone, Serono) has been used to treat 56 patients with clinical diagnosis of genital condylomatosis in quantity of 3 million UI/die. Controls have been effected at 3 months since the end of therapy. 30 patients were cured after 3 months of therapy, while at 6 months follow-up we have reported a complete regression in 78.6% of cases.

[New pharmacological approach to therapy of perimenopausal meno-metrorrhagia. Vaginal use of progesterone]. / Nuovo approccio farmacologico alla terapia delle meno-metrorragie peri-menopausali. Utilizzo del progesterone per via vaginale.

The authors evaluate the effectiveness of a therapy based on natural progesterone to be employed as a vaginal cream in the treatment of meno-metrorrhagia in peri-menopause in 40 patients who were not prepared to consider surgery as a solution for their problems. In the polycentric out-patient study this new preparation has proved to be efficacious and to induce a regression of the endometrial hyperplasia in more than 90% of patients subject to five months' treatment.

[Treatment with GnRH analogs in polycystic ovarian disease. A collaborative multicenter study. The preliminary results]. / Il trattamento con analoghi del GnRH della malattia policistica dell'ovaio. Studio policentrico collaborativo. Risultati preliminari.

The study evaluates the efficacy of tryptorelin treatment in cases of acne and hirsutism associated with polycystic ovarian (PCO) disease. This non-comparative open study in a sample population of 20 young patients who wished to have children demonstrates the reduction of the hirsutism and acne score after six months' treatment. Tryptorelin was even capable of normalizing the hematic hormonal levels examined and ovarian function following six months of treatment, as well as at an initial follow-up after three months. The authors state their intention of performing a larger trial in order to observe the real efficacy of tryptorelin in a study which includes a 12-month follow-up to assess the pregnancy rate.

[Therapy of simple endometrial hyperplasia with GnRH analogs. Evaluation of a multicentric ambulatory study. Preliminary results]. / Trattamento con GnRH analoghi della iperplasia endometriale semplice. Valutazione di uno studio policentrico ambulatoriale. Risultati preliminari.

Endometrial hyperplasia is a frequent pathology during menopause and involves the risk of malignant transformation of the lesions. In an attempt to avoid radical surgery, this study proposes the use of triptorelin which was used to treat 56 patients with histologically confirmed symptoms of endometrial hyperplasia without atypia. GnRH-analog was administered using the intramuscular route every 28 days for 6 months. Histological controls were carried out 30 days after the last injection and showed the resolution of histological symptoms, confirmed after three months.

[Correction of nose deviations using latero-septal grafts from irradiated bovine cartilage]. / Correction des nez déviés par greffes d'appui latéro-septal en cartilage bovin irradié.

Deviated noses corrective surgery is not without problems. Authors give the result obtained by the use of processed irradiated bovine cartilage (Chondroplast) as spreader graft in eighteen rhinoplasty, associated with a classical septorhinoplasty technique. The maximum background is five years. The future of the grafts can be appreciated on direct signs obtained by palpation, or indirect ones such as stability of the functional or aesthetic result, radiological visualisation of the bovine cartilage graft. Their volumetric stability is satisfactory and their guide role is excellent. This undisputed aid in the aesthetic and functional correction of deviated noses, associated with availability, easy use and a good tolerance, made the authors use spreader grafts in processed irradiated bovine cartilage as a choice technique in this indication, associated with bone and septal surgery, when local cartilage autografts are not available in sufficient quantities.

[Fluconazole in the treatment of vaginitis caused by Candida albicans]. / II Fluconazolo nel trattamento delle vaginiti sostenute da Candida albicans.

The authors verified the local activity and tolerance of the antimycotic drug Fluconazole in 125 cases of women suffering from clinical diagnosed vulvovaginitis caused by Candida albicans. Results were positive with regard to the efficacy and safety of the treatment.

[The effect of two contraceptive methods (EP vs. IUD) in relation to inflammatory changes and CIN]. / L'influenza di due metodiche contraccettive (EP versus IUD) nei confronti di alterazioni infiammatorie e CIN.

The authors examine Smear Test phlogistic picture repair processes, endometrial cells and preneoplastic lesions in women who used IUD and EP. The research has pointed out that infection due to Actinomyces is only (present) in IUD carriers. CIN affects for 4.2% of IUD carriers.

[Observations on bone mineral metabolism in natural and surgical menopause. Role of synthetic salmon calcitonin and calcium on bone turnover]. / Osservazioni sul metabolismo minerale osseo nella menopausa naturale e chirurgica. Ruolo della calcitonina sintetica di salmone e del calcio sul turnover osseo.

Loss of bone mass is a process which generally becomes manifest in women during the fourth decade of life and is considerably accelerated following the onset of menopause, especially if this in surgically induced. Bone mineral metabolism was studied in 104 women, subdivided into the following groups: group 1: 33 women with normal menstrual cycles; group 2: 30 women in pre-menopause; group 3: 38 women who had undergone ovariectomy but had not received any osteotrope treatment; group 4: 33 ovariectomised women who had been treated immediately after surgery with calcium (1 g/die per os) in addition to synthetic salmon calcitonin nasal spray (100 IU on alternate days). Patients in groups 2-4 were analysed on entry into the study (time 0) and after 6 and 12 months of menopause (natural or surgical) using biochemical tests (alkaline phosphatase, calcium and phosphorus metabolism, PTH and osteocalcin) and by calculating bone mineral content (BMC) using a single photon ray performed at 3 cm and 8 cm from the styloid apophysis of the radius. The groups were matched for age, body mass index, dietary and sexual habits, geographic area. The results obtained can be summarised as follows: a) the concentrations of the main biochemical parameters were found to be normal and substantially similar between all groups at time 0; however, after 12 months increments relating to alkaline phosphatase and osteocalcin were significantly higher in ovariectomised women who did not receive treatment compared to ovariectomised patients treated with calcium + calcitonin, thus indicating a lower bone turnover in the latter group. b) BMC values, measured at the distal radius.

[Allografts of cryo-preserved and radio-sterilized spongy bone tissue. Their use in orthognathic surgery]. / Les allogreffes de tissu osseux spongieux cryo-conservées et radio-stérilisées. Utilisation en chirurgie orthognathique.

In some circumstances, the orthognathic surgery creates inter-fragmentary spaces which have to be filled to ensure that the osteotomized segments are wedged and consolidated, and to avoid the appearance of unsightly subcutaneous contours. The authors report the results obtained through the use of cryo-preserved radio-sterilized cancellous bone allografts, coming from femoral heads, used as fillers, in diverse types of osteotomy. Thus, 19 centers of osteotomy have been filled. Follow-up periods ranged from 5 to 20 months. In 8 cases, evidence was made through radiology of the blending of the grafts. The stability of the correction was constantly noticed as well as the perfectly harmonious facial contours, which testifies the osteogenic qualities of this material. No sepsis was observed. It is a quantitatively available material, of easy shaping, the use of which does not lead to a lengthening of the operation, nor to the creation of cutaneous scars. The risk of viral transmission through allografts, specially H.I.V. and hepatitis non A - non B - non C virus is nil due to the radiosterilization.

GnRH receptors in human granulosa cells: anatomical localization and characterization by autoradiographic study.

The presence of receptors for GnRH in human ovary has been investigated by quantitative autoradiography. Simultaneous visualization and characterization of specific receptors on frozen sections were obtained on six pairs of human ovaries. Among them only one exhibited a large preovulatory follicle. This dominant follicle exhibited a specific and high affinity binding capacity for 125I-GnRHa exclusively localized on the granulosa cell layer. Analysis of saturation curve indicates a Kd value of 0.22 nM and Bmax of 9.6 fmol/mg protein. In contrast LH-hCG binding sites were present in all antral follicles. These data demonstrate for the first time the presence of high affinity GnRH receptors in human granulosa cells at a late stage of follicular maturation.

[Cancers of the soft palate. Results of repeat surgery]. / Cancers du voile du palais. Résultats de la chirurgie de rattrapage.

Between 1960 and 1983, 270 patients were treated at the CURIE Institute for a carcinoma of the soft palate, including 260 by radiotherapy (mean dose: 69 Gy). Most of these tumours were T1 T2 (201 cases, 76%). There was a high frequency of a past history of carcinoma (38 cases, 14%) as well as of simultaneous carcinomas (44 cases, 16%). Two months after radiotherapy, a velar tumor persisted in 29 patients whilst 1 patient had deep necrosis. 15 of these 30 patients underwent secondary surgical excision. This surgical series included 25 of 27 recurrences seen secondarily and 6 patients operated on for second velar carcinoma appearing in the irradiated zone (mean dose: 68 Gy). 45 of the 46 excisions were carried out by a buccal approach. Overall survival after surgery was 32% at 3 years. The 11 patients operated on for an extensive T3 T4 tumour died before 12 months. These poor results were related to the frequency of local recurrences (12 loco-regional failures amongst 36 deaths) as well as the number of deaths due to second carcinomas (11 deaths amongst the surgical patients). Later carcinomas were particularly frequent during the course of tumours of this site (69 cases out of 270), the problem of multiple malignant tumours finally affecting 122 patients out of 270, i.e. 45%.

Follow-up study of patients with respiratory disease due to toluene diisocyanate (TDI).

The outcome of the respiratory symptoms, pulmonary function tests and bronchial hyperresponsiveness was studied in forty-seven workers with respiratory disease due to toluene diisocyanate (TDI) (twenty-seven asthmatic and twenty non-asthmatic subjects) after about 2 years from the first examination. Eight of twelve asthmatic subjects who left the industry after the first examination complained at the follow-up of dyspnoea and wheezing, but pulmonary function tests were unchanged; bronchial hyperresponsiveness decreased in three, but most were still positive to challenge test with bethanechol at the follow-up. Fifteen subjects who continued their exposure to TDI showed at the follow-up a significant decrease of the spirometric parameters and an increase of the bronchial hyperresponsiveness, and symptoms of chronic bronchitis were more frequent at the second examination. Non-asthmatic subjects, both exposed and non-exposed to TDI at the second examination, showed a significant decrease of the pulmonary function tests but no relevant changes in bronchial hyperresponsiveness. Our data suggest that stopping occupational exposure to TDI frequently did not produce an improvement of the TDI bronchial asthma, and persistence of the occupational exposure causes a more rapid decline in the respiratory function.

[Validity of a specific bronchial provocation test with proteolytic enzymes in occupational bronchial asthma caused by enzymatic detergents]. / Validità di un test di broncostimolazione specifica con enzimi proteolitici nell'asma bronchiale professionale da detergenti enzimatici.

Six asthmatic subjects exposed to enzymatic detergents derived from B. Licheniformis were examined by means of a specific Bronchial Provocative Test (sBPT) with solutions of the enzyme. All subjects, except for one, were positive to prick tests with solutions of the "crude" enzyme and with Alcalase, and showed high levels of specific IgE by RAST. The sBPT with solutions of the enzyme, administered by means of a Bird Mark 7 nebulyzer in IPPB with measurement of the delivered dose, showed a positive response in all 6 subjects. No positive result was obtained in 5 normal subjects and in 5 non exposed asthmatic patients, even at much higher doses of the delivered enzyme. The occupational-type sBPT showed only two positive results out of the 6 examined. A good relationship was observed between bronchial hyperresponsiveness and provocative dose of the enzyme. Therefore, the sBPT with solutions of the enzyme is proved to be highly sensitive and specific in confirming the diagnosis of occupational asthma due to proteolytic enzymes.