Anticholinergic medications in patients admitted with cognitive impairment or falls (AMiCI). The impact of hospital admission on anticholinergic cognitive medication burden. Results of a multicentre observational study.

WHAT IS KNOWN AND OBJECTIVE: Drugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. METHODS: This is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. RESULTS AND DISCUSSION: 21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naïve patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR = 1.82, 95% CI for OR: 1.36-2.45, P < .001). WHAT IS NEW AND CONCLUSION: There was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.

No evidence of association between subclinical thyroid disorders and common carotid intima medial thickness or atherosclerotic plaque.

BACKGROUND AND AIMS: Increased carotid artery intima-media thickness (IMT) and the presence of plaques have been shown to be predictors of cardiovascular disease. The cardiovascular risk in patients with overt thyroid diseases is related to increased risk of atherosclerosis, but there has been no clear evidence about subclinical disorders. We have assessed whether subclinical thyroid dysfunction is associated with arterial thickening and plaque. METHODS AND RESULTS: The SardiNIA study is a population-based survey on the Italian island of Sardinia. We reviewed data from 5815 subjects (aged 14-102 years), none of whom had overt hyperthyroidism or hypothyroidism or was taking thyroid medication. Serum thyrotropin (TSH), free thyroxine, together with carotid ultrasound IMT and the presence of common carotid plaques were analysed in all subjects. Possible association of IMT and carotid plaques with thyroid parameters was evaluated by univariate and multivariate analyses. IMT was significantly associated with age, sex, smoking, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol, pulse pressure (PP), history of arterial hypertension, diabetes, and previous cardiovascular events (p = 0.001 or lower, R(2) = 0.47). Carotid plaques were predicted by age, sex, LDL, PP, history of diabetes, previous cardiovascular events, and the use of statins (p = 0.029 or lower). Thyroid hormone was not predictive of carotid atherosclerosis when adjusted for confounders. CONCLUSION: Thyroid hormone is not associated with increased IMT or with the presence of carotid artery plaque. Our data do not support the idea that treating subclinical disorders might help to prevent arterial remodelling or carotid atherosclerosis.

Age- and gender-specific awareness, treatment, and control of cardiovascular risk factors and subclinical vascular lesions in a founder population: the SardiNIA Study.

AIM: We investigated the gender-specific control of cardiovascular (CV) risk factors and subclinical vascular lesions in a founder population in Italy. METHODS AND RESULTS: 6148 subjects were enrolled (aged 14-102 years) from four towns. Hypertension (HT), diabetes mellitus (DM) and dyslipidemia (LIP) were defined in accordance with guidelines. A self-reported diagnosis defined awareness of these conditions, and the current use of specific medications as treatment. Prevalence was HT 29.2%, DM 4.8%, LIP 44.1% and was higher in men than in women. Disease prevalence increased with age for every CV risk factor. Men were less likely than women to take anti-HT drugs and to reach BP control (9.9% vs. 16%). Only 17.6% of HT > 65 years had a BP < or =140/90 mmHg, though 48.5% were treated. The use of statins was very low (<1/3 of eligible subjects > 65 years, those with the highest treatment rate). The ratio of control-to-treated HT was lower in subjects with, than in those without, thicker carotid arteries (31.5% vs. 38.8%, p < 0.05) or stiffer aortas (26.0% vs. 40.0%, p < 0.05) or carotid plaques (26.3% vs. 41.1%, p<0.05). CONCLUSION: A large number of subjects at high CV risk are not treated and the management of subclinical vascular lesions is far from optimal.

Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors.

Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP-induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined.

Degradation and leaching of the herbicides metolachlor and diuron: a case study in an area of Northern Italy.

In this work the degradation of the herbicides metolachlor, diuron, monuron and of the metabolites 2-ethyl-6-methylaniline (EMA), and 3,4-dichloroaniline (DCA) was assessed in laboratory experiments on microbiologically active and sterilized soils. Their leaching potentials were calculated, using Gustafson's equation, by determining their mobility (as Koc) and persistence (expressed as DT50). Lysimeter experiments were also conducted to assess the actual leaching of the studied herbicides in a cereal crop tillage area vulnerable to groundwater contamination. The data obtained from the field were compared to the laboratory results. Moreover, some compounds of particular concern were searched for in the groundwater located near the experimental area in order to evaluate actual contamination and to test the reliability of the leaching potential. The GUS index, computed on data from microbiologically active soil, shows monuron as a leacher compound, EMA and DCA as non-leachers, metolachlor and diuron as transient ones. The presence of metolachlor in the groundwater monitored, even at concentrations up to 0.1 mug/l, confirms the possibility that transient compounds can be leached if microbial activity has not completely occurred in active surface soil.

Melatonin enhances the luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the follicular, but not in the luteal, menstrual phase.

Exogenous melatonin enhances LH pulse amplitude and mean LH levels in women during the follicular, but not the luteal, menstrual phase. In this study we investigated whether an increased pituitary response to GnRH is involved in the stimulatory effect of melatonin. Eight normal cycling women were studied on 2 consecutive days during the follicular stage (days 4-6), and eight were studied during the luteal phase (days 19-21) of the menstrual cycle. On 2 consecutive days, each women received, randomly and in a double blind fashion, placebo or 3 mg melatonin (1 mg at 0800, 1000, and 1200 h), whereas the pituitary LH and FSH responses to GnRH were tested by the iv administration of three submaximal doses of GnRH (1 microgram at 0900 h, 5 micrograms at 1100 h, and 10 micrograms at 1300 h). In the follicular phase, melatonin administration enhanced the LH and FSH responses to all three GnRH stimuli, whereas in the luteal phase, melatonin administration was ineffective. The present data indicate that an enhancing effect of melatonin on the LH and FSH responses to submaximal GnRH stimuli is evident in the follicular, but not the luteal, phase of the menstrual cycle and infer an endocrine window for the effect of melatonin on gonadotropin secretion.

Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel.

Oral contraceptives slightly deteriorate insulin sensitivity. The present study investigated whether they may further unbalance the glucose metabolism of lean women with polycystic ovary syndrome (PCOS). Women with PCOS were assigned to receive for 6 months the biphasic association of 40/30 micro g ethinyl estradiol (EE) and 25/125 micro g desogestrel (DSG; n = 10) or the monophasic association of 35 micro g EE and 2 mg cyproterone acetate (CPA; n = 10). Glucose tolerance was investigated by an oral glucose tolerance test (OGTT). Glucose utilization dependent [insulin sensitivity (SI)] or independent (Sg) of insulin was investigated by the minimal model method applied to a frequently sampled iv glucose tolerance test. EE/DSG increased the response of C peptide to OGTT (1413 +/- 113 vs. 2053 +/- 213 area under the curve; P < 0.009) and the C peptide/insulin ratio (0.085 +/- 0.01 vs. 0.134 +/- 0.01 area under the curve; P < 0.003). It also increased the Sg (0.026 +/- 0.002 vs. 0.034 +/- 0.003; P < 0.04) and decreased the SI (2.40 +/- 0.26 vs. 1.68 +/- 0.27; P < 0.01). EE/CPA did not modify responses to OGTT of glucose, insulin, C peptide, or C peptide/insulin ratio. It did not modify Sg and significantly increased SI (1.47 +/- 0.38 vs. 3.27 +/- 0.48; P < 0.04). The present study indicates that EE/CPA improves SI, whereas EE/DSG impairs SI, but improves insulin clearance. The long-term metabolic effects of these two compounds on women with PCOS require further investigations.

Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause.

The psychological symptoms assessed with a validated psychometric scale, SCL-90, were significantly higher in postmenopausal women (PMW; 60 subjects) than in premenopausal women (20 subjects). In the same PMW, the activity of the dopaminergic system, assessed with the PRL response to the dopamine-blocking agent sulpiride, was significantly lower than that in premenopausal women. During a period of 12 weeks the 60 PMW were randomly divided into 3 groups: no treatment (group A; n = 20), treatment with estradiol (E(2)) alone (patches with a E(2) release of 50 microg/24 h; group B; n = 20), and treatment with hormonal replacement therapy [estradiol valerate (EV) at a daily dose of 2 mg for 11 days and EV at the same daily doses plus cyproterone acetate (CPA) at a daily dose of 1 mg/day for 10 days; group C; n = 20). At the 12th week of the observation, only in group C women were the psychological symptoms significantly decreased, and the indirect evaluation of the dopaminergic system activity through PRL response to sulpiride showed a significant increase. During the same period, no changes in testosterone levels were observed in any group of PMW, whereas a significant increase in E(2) levels was found in both groups B and C. Although it is likely that the improvement in psychological symptoms with EV and CPA was due to progestin, we cannot rule out the possibility that greater estrogen exposure may have played a role.

Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy.

OBJECTIVE: To evaluate the effectiveness of vaginal danazol as progestin supplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), estrogen alone, and placebo. METHODS: Forty healthy women at least 12 months after natural menopause were randomly divided into four treatment groups: Group 1 (n=10), continuous transdermal estradiol (TE) (50 microg/day), plus a monthly 10-day course of MPA (10 mg/day); Group 2 (n=10), continuous TE plus a monthly 10-day course of vaginal danazol (200 mg/day); Group 3 (n=10), TE alone; Group 4 (n=10), placebo. At baseline and during the first, third, and sixth month of treatment, the endometrial thickness was assessed by transvaginal ultrasonography, while the pulsatility index (PI) of the carotid and uterine arteries was assessed by color Doppler. An endometrial biopsy was also performed before and after the treatment. RESULTS: At baseline, no significant differences between ages and other evaluated parameters were present in the four groups. In groups 1, 2, and 3, the values of carotid and uterine PI decreased significantly and similarly during the treatment, while in group 4 they were unchanged. In group 3 only, the endometrium was significantly thicker during treatment than before. No endometrial hyperplasia was present in the four groups at the end of the treatment. CONCLUSIONS: Vaginal danazol seems to be capable of counteracting the mitogenic effect of estrogen on the endometrium without reducing the effectiveness of estrogens to improve peripheral arterial perfusion.

Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism.

OBJECTIVE: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. PATIENT(S): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). INTERVENTION(S): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. MAIN OUTCOME MEASURE(S): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. RESULT(S): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. CONCLUSION(S): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.

The chronic administration of cabergoline normalizes androgen secretion and improves menstrual cyclicity in women with polycystic ovary syndrome.

OBJECTIVE: To investigate whether the administration of the long-lasting dopaminergic drug, cabergoline, improves endocrine and clinical features of women with polycystic ovary syndrome (PCOS). PATIENTS: Twenty-nine women participated in the study: 14 women with clinical and endocrinologic features of PCOS and 15 age- and weight-matched normal cycling women. Each subject was assigned randomly to receive either a tablet of cabergoline at the dose of 0.5 mg/wk or placebo for 4 months. Sixteen subjects (PCOS: n = 8; controls: n = 8) received cabergoline, whereas 13 (PCOS: n = 6; controls: n = 7) received placebo. INTERVENTIONS: Both before and during the 4th month of treatment, blood samples were collected every 10 minutes from 9:00 A.M. to 3:00 P.M., 3 to 7 days after spontaneous or medroxy-progesterone acetate (MPA; 5 mg daily for 5 days)-induced menses. Follicle-stimulating hormone and androgen levels were measured in the basal samples, whereas LH levels were measured in all samples. MAIN OUTCOME MEASURES: Menstrual cyclicity, LH pulsatility, and circulating levels of FSH, PRL, E2, total T, free T, androstenedione, 17 alpha-hydroxyprogesterone, DHEAS, and sex hormone-binding globulin. RESULTS: Both in controls and in PCOS-affected women, cabergoline administration blunted plasma PRL levels without affecting LH pulsatility. Androgen levels were reduced in controls and normalized in PCOS. Cabergoline, but not placebo, induced menses reappearance in amenorrheic and a normalization of menstrual cyclicity in oligoamenorrheic women with PCOS. CONCLUSIONS: The administration of cabergoline is capable to normalize androgen levels and to improve menstrual cyclicity in PCOS-affected women. Cabergoline may represent an useful treatment for menstrual irregularities of PCOS patients.

Evidence that an altered prolactin release is consequent to abnormal ovarian activity in polycystic ovary syndrome.

OBJECTIVE: To investigate whether endogenous dopaminergic activity is impaired in polycystic ovary syndrome (PCOS)-affected women and is normalized by medical ovariectomy. PATIENTS: Women with PCOS untreated (n = 23) and treated for 3 months with GnRH analogue (GnRH-a) administration (n = 10) and normal cycling young women (n = 23) as controls. INTERVENTIONS: Acute blockade of dopaminergic receptors by the IV administration of 5 mg of the dopaminergic receptor blocking agent sulpiride (sulpiride test) was performed 3 to 7 days after the initiation of spontaneous menses in cycling women or medroxyprogesterone acetate-induced menses in PCOS women. In PCOS women treated with GnRH-a administration (goserelin depot, 3.6 mg SC every 28 days), the sulpiride test was repeated 10 to 15 days after the third GnRH-a administration. MAIN OUTCOME MEASURE: Basal PRL levels and PRL increase induced by sulpiride. RESULTS: Basal PRL levels and the PRL response to sulpiride were increased in women with PCOS. In women with PCOS medical ovariectomy induced by GnRH-a administration reversed to normal both basal and sulpiride-stimulated PRL levels. CONCLUSIONS: In women with PCOS the abnormal regulation of PRL and presumably of hypothalamic neurotransmitters controlling PRL secretion is not a primary alteration but it is likely dependent on abnormal ovarian functionality.

Psychopharmacological treatment of depression, anxiety, irritability and insomnia in patients receiving interferon-alpha: a prospective case series and a discussion of biological mechanisms.

We studied 60 patients receiving a 1-year course of interferon (IFN)-alpha therapy for chronic viral hepatitis. Patients underwent psychiatric assessment before starting the IFN-alpha therapy, and monthly throughout the therapy, using the Structured Clinical Interview for the DSM-III-R, the 17-item Hamilton Depression Rating Scale, the Beck Depression Inventory and the Spielberg State and Trait Anxiety Inventory. Five patients had a baseline diagnosis of major depression and 18 (30%) developed an IFN-alpha-induced psychiatric adverse effect; 12 of these 23 patients received psychopharmacological treatment (patients and clinicians jointly decided the need for treatment). Two of the five patients with baseline depression started an antidepressant treatment (paroxetine) together with the IFN-alpha and successfully completed the IFN-alpha therapy. Ten patients received treatment for the IFN-alpha-induced psychiatric adverse effects (depression in five patients, anxiety in two patients, severe irritability in two patients and insomnia in one patient). Depression was treated with paroxetine, amisulpride or levosulpiride; anxiety and insomnia were treated with benzodiazepines; and irritability was treated with thioridazine. Individual response to medications was measured with the Clinical Global Impression scale. Of the patients with IFN-alpha-induced depression, two received paroxetine (one showed a good response), two received amisulpride (one showed a good response) and one did not respond to levosulpiride but responded to paroxetine. The patients experiencing anxiety or insomnia responded well to benzodiazepines. One patient showed a good response, and one a poor response, to thioridazine for irritability. Only one patient interrupted the therapy because of psychiatric adverse effects. Overall, the 12 patients that received psychopharmacological treatment developed less severe psychopathological symptoms during the IFN-alpha therapy compared to the 11 patients who had untreated baseline depression or untreated IFN-alpha-induced psychiatric adverse effects. Thus, psychopharmacological management can successfully treat psychiatric symptoms in patients who are receiving IFN-alpha.

Evidence that treatment with monophasic oral contraceptive formulations containing ethinylestradiol plus gestodene reduces bone resorption in young women.

The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound (gestodene, GES, 75 microg) but different doses of ethinylestradiol (EE2) (20 or 30 microg) differently influences specific markers of bone resorption (urinary levels of pyridinoline (PYR) and dexoxypyridinoline (D-PYR)). During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women (subjects of the same age group with normal menstrual cycle who did not use contraception). In women taking pills with 20 or 30 microg EE2, the levels of sex hormone-binding globulin (SHBG) significantly increased during treatment in comparison with baseline, whereas in the same time period no changes occurred in control women. These findings suggest that similar to the pill containing 30 microg EE2, the lower dosage of the EE2 pill (20 microg) is also capable of reducing bone resorption. Twenty and 30 microg EE2 pills exert the same biological estrogenic effect. In fact, SHBG levels significantly increased with both pills. However, an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone cannot be excluded. Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects, these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice.

PIP: The aim of this study was to evaluate if a pill containing the same dose of the same type of progestin compound (gestodene, GES, 75 mcg) but different doses of ethinyl estradiol (EE2) (20 or 30 mcg) differently influences specific markers of bone resorption (urinary levels of pyridinoline (PYR) and dexoxypyridinoline (D-PYR). During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young postadolescent women taking the pills with 20 or 30 mcg EE2 in comparison with control women (subjects of the same age group with normal menstrual cycles who did not use contraception). In women taking pills with 20 or 30 mcg EE2, the levels of sex hormone-binding globulin (SHBG) significantly increased during treatment in comparison with baseline, whereas in the same time period no changes occurred in control women. These findings suggest that similar to the pill containing 30 mcg EE2, the lower dosage of the EE2 pill (20 mcg) is also capable of reducing bone resorption. 20 and 30 mcg EE2 pills exert the same biological estrogenic effect. In fact, SHBG levels significantly increased with both pills. However, an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone cannot be excluded. Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects, these findings further suggest that a pill containing 20 mcg EE2 would be the best choice for young postadolescent women.

Solubility and thermal stability of some amino-mellitate compounds.

By reaction between the anion of mellitic acid (benzenehexacarboxylic acid) and some protonated linear polyamines (diethylenetriamine, triethylenetetramine, tetraethylene-pentamine, pentaethylenehexamine, spermidine, and spermine), fairly insoluble complexes have been obtained, with the general formula (amine)(x)(mellitate)H(6) (diethylenetriamine and spermidine, x=1; triethylenetetramine and spermine, x=0.75; tetraethylenepentamine, x=0.6 and 0.8; pentaethylenehexamine, x=0.5). K(s0) values for these complexes have been determined at I=0 mol dm(-3) and T=25 degrees C (logK(s0) ranges between -48.2 and -56.6). The solubility has been studied as a function of pH and of ionic strength. The thermal analysis, performed using air or argon flow, showed that all the solids behave in a similar way. In the range 20-120 degrees C the loss of hydration water occurs, and in the range 150-350 degrees C the first step of non oxidative decomposition takes place, with complete decomposition at 650 degrees C in air flow, whilst in argon flow the decomposition is still incomplete at 900 degrees C. Preliminary results of a parallel diffractometric study are also reported.

Detection of isoniazid and rifampin resistance in Mycobacterium tuberculosis strains by single-strand conformation polymorphism analysis and restriction fragment length polymorphism.

Anti-Mycobacterium tuberculosis drug-resistance, mainly multi-drug resistance (MDR-TB), represents an important public health problem in several countries. Aim of our study is to identify the presence of these mutations in M. tuberculosis isoniazid- and rifampin-resistant strains isolated in our Institute; to evaluate linkage between type of mutation and level of resistance; to determine the usefulness of easy molecular techniques for rapid detection of such mutations on body specimens. Isoniazid- and rifampin-resistance was tested on 67 M. tuberculosis strains by Single-Strand Conformation Polymorphism (SSCP) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assays, using HaeIII, PstuI, BsteII, BstuI enzymes. Drug-resistance of control strains was determined by cultural techniques (fluorimetry- BACTEC 9120). Cultural assay showed isoniazid- and rifampin-resistance in 6.12 and 2%, respectively (data confirmed by SSCP assay). Mutation of katG, linked to isoniazid resistance, was detected using BstuI enzyme, and mutation of rpoB, expression of reduced sensitivity to rifampin, using HaeIII. 15 body specimens, M. tuberculosis-positive to conventional assays, were tested by SSCP technique. Epidemiologic reports of numerous cases of tuberculosis due to MDR strains induce to detect quickly both Mycobacteria and drug-resistance, in order to start prompt effective therapy. On this basis, molecular assays are useful for a rapid therapeutic decision.

[Early diagnosis of endometrial carcinoma and its precursors in asymptomatic postmenopausal women. Proposal of a diagnostic protocol]. / Diagnosi precoce del carcinoma endometriale e dei suoi precursori in donne asintomatiche in postmenopausa. Proposta di un protocollo diagnostico.

BACKGROUND: Endometrial carcinoma is presently the most frequent malignant tumor of the female genital tract. In most cases it concerns menopausal women mostly affected by chronic hyperestrogenism not balanced by progesterone. Among the useful techniques for early diagnosis in asymptomatic postmenopausal patients, only echography and hysteroscopy have obtained high reliability levels. Particularly the echographic evaluation of the endometrial thickness is the technique on which the screening of asymptomatic patients should concentrate. Nonetheless its employment on so many people would involve too expensive a social cost. METHODS: In the attempt to identify a limited group of patients to undergo the echographic test, the authors have determined, in a group of 330 asymptomatic postmenopausal women, the maturation degree of squamous cells in PAP-Smear executed for the prevention of the cervical carcinoma, in order to select subjects through a suitable estrogenic stimulation. In cases of high maturation degree (16%) and in a compared group of examinations, a progestin test (MAP-Test) has been carried out to verify the presence of possible pathological endometrial proliferation. They have thus identified a small group of asymptomatic women (6%) to undergo transvaginal echography. In this way 1.8% of the examined patients have undergone hysteroscopy with guided biopsy because of a high risk of carcinoma. RESULTS: The prevalence of endometrial carcinoma so detected was 3/1000. CONCLUSIONS: The authors, intend to continue their experience, end by hoping that protocol adopted by them, should become part of a global prevention program for gynecological oncology.

The treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women in reproductive age. As for the treatment of this disease the lack of a clear etiology for PCOS has led to a symptom-orientated treatment. However, the overall aims of treatment are to induce ovulation for women desiring conception, to reduce androgen levels, to reduce body weight and to reduce long-term health risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is recommended as first line treatment for induction of ovulation in patients with PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives for CC-resistant patients include gonadotrophin therapy (better with low-dose step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH (rFSH) has been introduced in clinical practice and it seems more effective than urinary FSH as demonstrated by a significantly higher number of follicles recruited and embryos obtained with a shorter treatment period. The addition of GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce premature luteinization and increase cycle fecundity. Other drugs under investigation are metformin and cabergoline. Hirsutism is the manifestation of hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is central or peripheral androgen suppression using 3 groups of drugs: inhibitors of androgen production (oral contraceptives, GnRH analogues), peripheral androgen blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and insulin-sensitizing agents (metformin). Weight reduction and exercise could also improve not only menstrual disturbances and infertility, but also insulin resistance and its adverse metabolic con-sequences.

Prognostic value of hCG, progesterone, 17-beta estradiol and the echoscopic examination in threatened abortion during the first trimester.

The Authors refer on the validity of echoscopic examination and hCG, progesterone and 17-beta estradiol values in the prognosis of threatened abortion during the first trimester of pregnancy in 62 patients. The echoscopic examination allowed a prognosis to be made in accordance with the clinical evolution of threatened abortion in 90% of the cases; the plasma levels of hCG and progesterone in 87% of the cases; 17-beta estradiol in 83% of the cases. The Authors conclude that the simultaneous assay of hCG, progesterone and 17-beta estradiol plasma levels does not improve the prognostic validity of echoscopy but, in some cases, can provide essential details on the etiology of threatened abortion itself.

[Multiple sclerosis and major depression resistant to treatment. Case of a patient with antidepressive therapy-induced mood disorder, associated with manic features]. / Sclerosi multipla e depressione maggiore resistente al trattamento. Il caso di una paziente con disturbo dell'umore indotto dalla terapia antidepressiva, con caratteristiche maniacali.

Patients with multiple sclerosis show higher prevalence of psychiatric disorders compared to general population, that are hardly managed by pharmacotherapy. In the present report a female patient, 44 years old, with diagnosis (according to DSM-IV) of 340 multiple sclerosis, 296.32 major depressive disorder, recurrent, moderate, 292.84 antidepressant-induced mood disorder, with manic features, is described. In this patient depressive symptoms did not respond to a number of drugs, including tricyclic antidepressants, selective serotonine re-uptake inhibitors hand lithium. Moreover, she had hypomanic and manic episodes induced by two different antidepressant, hydroxy-tryptophan and clorimipramine. Until today, only amisulpride (50 mg/die for four months, then 50 mg every two days for two months) has shown a significant effect on depressive symptomatology, moreover, this drug has not induced the occurrence of manic symptoms.