Improving adherence to and persistence with oral therapy of osteoporosis.

UNLABELLED: Osteoporosis treatment has low adherence and persistence. This study evaluated if greater patient involvement could improve them. At 12 months, only 114 out of 344 participants were "fully adherent and persistent" (all drug doses taken throughout the study). Only frequency of drug administration had a significant influence on adherence. INTRODUCTION: Osteoporosis affects millions of individuals worldwide. There are now several effective drugs, but adherence to and persistence with treatment are low. This 12-month multicenter, prospective, randomized study evaluated the efficacy of two different methods aimed at improving adherence and persistence through greater patient involvement, compared with standard clinical practice. METHODS: Three hundred thirty-four post-menopausal women, receiving an oral prescription for osteoporosis for the first time, were recruited and randomized into three groups: group 1 (controls, managed according to standard clinical practice) and groups 2 and 3 (managed with greater patient and caregiver involvement and special reinforcements: group 2, instructed to use several different "reminders"; group 3, same "reminders" as group 2, plus regular phone calls from and meetings at the referring Center). All enrolled women had two visits (baseline and 12 months). RESULTS: Of 334 enrolled women, 247 (74%) started the prescribed therapy. Of those who started, 219 (88.7%) persisted in therapy for at least 10 months. At final evaluation, only 114 women were considered as "fully adherent and persistent" (all doses taken throughout the 12 months). There were no significant differences regarding "full adherence" among the three randomized groups. The frequency of drug administration had a significant influence: weekly administration had a >5-fold higher adherence and monthly administration an 8-fold higher adherence (p < 0.0001) than daily administration. CONCLUSIONS: The special effort of devising and providing additional reminders did not prove effective. Additional interventions during the follow-up, including costly interventions such as phone calls and educational meetings, did not provide significant advantages.

Immunohistochemical expression study of proapoptotic BH3-only protein bad in canine nonneoplastic tissues and canine lymphomas.

The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. These findings warrant further investigations of the functional status, the involvement of partner proteins, and a possible impact of Bad on prognosis in canine lymphoma.

Cognitive remediation and functional improvement in schizophrenia: Is it a matter of size?

BACKGROUND: Cognitive Remediation represents the best available tool to treat cognitive deficits in schizophrenia and evidence suggests an effect also on global functioning. However, the relationship between cognitive and functional improvement is not yet fully elucidated: do cognitive changes need to be of a definite size and/or encompass a certain number of domains in order to impact on daily functioning? This study aims to explore the role of cognitive improvement, evaluated both quantitatively and qualitatively through the use of Italian equivalent scores, on the daily functioning of patients. As secondary goal, the influence of demographic, clinical and neuropsychological variables on functional outcome was also systematically investigated. METHODS: One hundred subjects with a diagnosis of schizophrenia underwent 36 sessions of Cognitive Remediation and were evaluated at baseline and after the training with the Brief Assessment of Cognition in Schizophrenia and the Quality of Life Scale. RESULTS: A total of 70% of patients improved in at least one cognitive domain and over 50% obtained a normalized score. Among the clinical and neurocognitive factors examined, the only significant predictor of quality of life's improvement was the proportion of cognitive functions that reached an equivalent score of "normal". CONCLUSIONS: This study suggests that improvements in daily functioning depend on the achievement of a cognitive profile as much as possible "normal", harmonious and balanced, supporting the idea that a qualitative leap in cognition is needed in order to gain an advantage in real life activities.

Sequence and partial functional analysis of canine Bcl-2 family proteins.

Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy. We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins.

An experimental model of diabetes and cancer in rats.

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.

Total respiratory system, lung, and chest wall mechanics in sedated-paralyzed postoperative morbidly obese patients.

OBJECTIVE: To study the relative contribution of the lung and the chest wall on the total respiratory system mechanics, gas exchange, and work of breathing in sedated-paralyzed normal subjects and morbidly obese patients, in the postoperative period. SETTING: Policlinico Hospital, University of Milan, Italy. METHODS: In ten normal subjects (normal) and ten morbidly obese patients (obese), we partitioned the total respiratory mechanics (rs) into its lung (L) and chest wall (w) components using the esophageal balloon technique together with airway occlusion technique, during constant flow inflation. We measured, after abdominal surgery, static respiratory system compliance (Cst,rs), lung compliance (Cst,L), chest wall compliance (Cst,w), total lung (Rmax,L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the component due to viscoelastic phenomena of the lung tissue and time constant inequalities (pendelluft). Functional residual capacity (FRC) was measured by helium dilution technique. RESULTS: We found that morbidly obese patients compared with normal subjects are characterized by the following: (1) reduced Cst,rs (p < 0.01), due to lower Cst,L (55.3 +/- 15.3 mL x cm H2O-1 vs 106.6 +/- 31.7 mL x cm H2O-1; p < 0.01) and Cst,w (112.4 +/- 47.4 mL x cm H2O-1 vs 190.7 +/- 45.1 mL x cm H2O-1; p < 0.01); (2) increased Rmin,L (4.7 +/- 3.1 mL x cm H2O x L-1 x s; vs 1.0 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01) and DR,L (4.9 +/- 2.6 mL x cm H2O x L-1 x s; vs 1.5 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01); (3) reduced FRC (0.665 +/- 0.191 L vs 1.691 +/- 0.325 L; p < 0.01); (4) increased work performed to inflate both the lung (0.91 +/- 0.25 J/L vs 0.34 +/- 0.08 J/L; p < 0.01) and the chest wall (0.39 +/- 0.13 J/L vs 0.18 +/- 0.04 J/L; p < 0.01); and (5) a reduced pulmonary oxygenation index (PaO2/PAO2 ratio). CONCLUSION: Sedated-paralyzed morbidly obese patients, compared with normal subjects, are characterized by marked derangements in lung and chest wall mechanics and reduced lung volume after abdominal surgery. These alterations may account for impaired arterial oxygenation in the postoperative period.

Performance of a hydrophobic heat and moisture exchanger at different ambient temperatures.

OBJECTIVE: To evaluate the effect of different room temperatures on hydrophobic heat and moisture exchangers (HME) humidifying capability and efficiency. METHODS: Stock HMEs were tested in vitro using an already described test model, with separation of inspiratory and expiratory gas. Absolute humidity (AH) was measured by means of dry-wet dual thermocouple, and HME efficiency was computed as the ratio between expired to inspired AH, at room temperature of 20 and 26 degrees C. RESULTS: Inspired gas temperature and AH were significantly higher at 26 than at 20 degrees C; since expired AH remained substantially unchanged, HME efficiency was also higher in warmer environment. CONCLUSIONS: Hydrophobic HMEs appear to be affected by room temperature, increasing their humidifying ability and their efficiency with its rise.

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients.

The effects of inspiratory flow and inflation volume on the mechanical properties of the respiratory system in eight sedated and paralyzed postoperative morbidly obese patients (aged 37.6 +/- 11.8 yr who had never smoked and had normal preoperative seated spirometry) were investigated by using the technique of rapid airway occlusion during constant-flow inflation. With the patients in the supine position, we measured the interrupter resistance (Rint,rs), which in humans probably reflects airway resistance, the "additional" resistance (delta Rrs) due to viscoelastic pressure dissipation and time-constant inequalities, and static respiratory elastance (Est,rs). Intra-abdominal pressure (IAP) was measured by using a bladder catheter, and functional residual capacity was measured by the heliumdilution technique. The results were compared with a previous study on 16 normal anesthetized paralyzed humans. Compared with normal persons, we found that in obese subjects: 1) functional residual capacity was markedly lower (0.645 +/- 0.208 liter) and IAP was higher (24 +/- 2.2 cmH2O); 2) alveolar-arterial oxygenation gradient was increased (178 +/- 59 mmHg); 3) the volume-pressure curve of the respiratory system was curvilinear with an "inflection" point; 4) Est,rs, Rint,rs, and delta Rrs were higher than normal (29.3 +/- 5.04 cmH2O/l, 5.9 +/- 2.4 cmH2O.l-1.s, and 6.4 +/- 1.6 cmH2O.l-1.s, respectively); 5) Rint,rs increased with increasing inspiratory flow, Est,rs did not change, and delta Rrs decreased progressively; and 6) with increasing inflation volume, Rint,rs and Est,rs decreased, whereas delta Rrs rose progressively. Overall, our data suggest that obese subjects during sedation and paralysis are characterized by hypoxemia and marked alterations of the mechanical properties of the respiratory system, largely explained by a reduction in lung volume due to the excessive unopposed IAP.

[Caloric intake and distribution of the main nutrients in a population of obese children]. / Introito calorico e ripartizione dei principali nutrienti in una popolazione infantile obesa.

Calorie intake and the main nutrient contents were assessed in a population of 152 obese (OB) children (86 M; 66 F; age 7-11) and 153 normal weight (NW) peers (87 M; 66 F). The following method was used: a) an interview using a food dictionary to assess food intake during the 2 days prior to the study and on one holiday: and b) a weekly questionnaire. The mean food intake of OB did not exceed that of NW, but on the contrary was lower (OB: 1812.9 +/- 39.6 kcal/die; NW: 1928.5 +/- 39.4 kcal/die; p less than 0.05). The population studied consumed approximately 50% of calories as carbohydrates (CHO), 35% as fats (F) and 15% as protein (P), and no difference was noted between OB and NW. The percentage of CHO was lower than that recommended by LARN, whereas the percentages of F and P were higher. A significant increase with age was noted in F and P intake as was a significant reduction of CO. 70% of OB and 80% of NW matched or exceeded the calorie intake recommended by LARN. 30% of OB and 24% of NW consumed 30% less than the daily calorie intake recommended by LARN.

Characterization of the immunophenotype and the metastatic properties of a murine T-lymphoma cell line. Unexpected expression of cytoplasmatic CD4.

We report the first characterization of a mouse T-lymphoma cell line that surprisingly expresses cytoplasmatic (cy) yCD4. Phenotypically, LBC cells are CD5+, CD8+, CD16+, CD24+, CD25+, CD2-/dim, CD3-/dim, TCRbeta-/dim, TCRgammadelta, CD154 , CD40-, and CD45R. Coexpress cyTCRbeta, cyCD3, cyCD4, and yet lack surface CD4 expression. Transplantation of LBC cells into mice resulted in an aggressive T-lymphoblastic lymphoma that infiltrated lymph nodes, thymus, spleen, liver, ovary, and uterus but not peripheral blood or bone marrow. LBC cells display a modal chromosome number of 39 and a near-diploid karyotype. Based on the characterization data, we demonstrated that the LBC cell line was derived from an early T-cell lymphocyte precursor. We propose that the malignant cell transformation of LBC cells could coincide with the transition stage from late double-negative, DN3 (CD4- CD8 CD44-/low, CD25+) or DN4 (CD4-low, CD8-/low, CD44-, CD25-) to double-positive (DP: CD4+CD8+) stage of T-cell development. LBC cells provide a T-lymphoblastic lymphoma model derived from a malignant early T-lymphocyte that can be potentially useful as a model to study both cellular regulation and differentiation of T-cells. In addition, LBC tumor provides a short latency neoplasm to study cellular regulation and to perform preclinical trials of lymphoma-relatel clisorders.

High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions.

Arterial hypertension is widely applied to improve regional cerebral blood flow (rCBF). We measured local brain tissue O2 pressure (PtiO2) in low density lesions at computerized tomography (CT) of the head before and after manipulation of mean arterial pressure (MAP) in order to increase cerebral perfusion pressure (CPP). Nine patients, 7 subarachnoid hemorrhage (SAH), 1 severe head injury, 1 meningeoma, were included in our study. A flexible polarographic microcatheter for PtiO2 measurement was placed at the border of the low density area found at CT. PtiO2 was continuously measured for 615 hours. Hypoperfusion in low density areas was detected by perfusional single photon emission computed tomography (SPECT). We recorded 22 episodes of induced or spontaneous increase of MAP. Initial PtiO2 regularly improved after the CPP increase (r2 0.74 in induced episodes). Low PtiO2 showed a greater percent increase for unitary changes of CPP than normal-high PtiO2. Baseline PtiO2 below 20 mm Hg was associated with normal CPPs; 5 readings of PtiO2 below 20 mm Hg normalized when a higher CPP was obtained. Our results show that in ischemic areas PtiO2 is dependent on CPP suggesting both a derangement of pressure autoregulation and high regional cerebrovascular resistences (CVRs). Low PtiO2 was associated with normal CPP, thus indicating that CPP could be an inadequate estimate of rCBF in focal ischemic areas. Arterial hypertension, capable of increasing CPP above normal values, appeared useful in normalizing tissue oxygenation in ischemic areas.

Epidemiological associations between arsenic and cancer in Argentina.

The population of a large central area of Argentina is affected by a syndrome designed as "regional and endemic chronic hydroarsenicism." A number of types of neoplasms, especially of skin, urinary bladder, and of digestive system, occur with higher frequency in these areas. Drinking water in some of the affected areas contains from 0.1 to 1.2 mg/L of As.

[Video laparoscopic cholecystectomy in a female patient with cholelithiasis in Steinert's myotonic dystrophy]. / Colecistectomia videolaparoscopica in paziente affetta da colelitiasi in distrofia miotonica di Steinert.

Steinert's disease (SD) is a rare (3-5/100000) myotonic myopathy responsible for chronic restrictive respiratory insufficiency and dilatative myocardiopathy. The authors report the case of a 52-years-old female patient with SD who underwent laparoscopic cholecystectomy for cholelithiasis. Postoperative course was uneventful and the patient was discharged after 4 days. Laparoscopic surgery was effective and safe in the treatment of this pathology.

Radioprotective potential of histamine on rat small intestine and uterus.

The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239 ± 12 vs 160 ± 10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radioprotective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.

Binge eating disorder in obesity: comparison of different therapeutic strategies.

The aim of this study (duration: 12 months) was to compare different integrated therapeutic approaches for the therapy of Binge Eating Disorder (BED). A sample of 65 female severely obese BED was randomly divided into 3 groups: the first one was treated by Cognitive-Behavioural Therapy (CBT) alone; the second one was treated by SSRI antidepressant therapy (fluoxetine) alone; the remaining was treated by a combination of CBT plus fluoxetine. All groups received group nutritional training and individual dietary counselling. The initial fluoxetine dose (20 mg/day) was adjusted (up to 60 mg/day) according to frequency of binge eating. During the first 4 weeks, all subjects underwent an in-patient dietary treatment aimed to achieve at least a 5% weight loss, which was continued during the out-patient treatment phase. At the beginning and at the end of the therapy the patients were evaluated by the Minnesota Multiphasic Personality - 2 and by the Eating Disorder Inventory - 2. The results showed that the two groups which underwent psychotherapy resulted in a better outcome - in terms of number of bingeing episodes, maintenance of weight loss reduction from baseline and psychological well being - than the group treated with pharmacological therapy alone. Finally, the study underlines the importance of a multidisciplinary approach to the treatment of Binge Eating Disorder.

[Assisted ventilation: experimental evaluation in vitro]. / Ventilazione assistita: valutazioni sperimentali in vitro.

OBJECTIVE: During assist-control mode ventilation (AMV), patients perform external excess work (Wex) to activate the mechanical ventilator itself. Aim of the study was to quantitate such a Wex and evaluate the best ventilator setting in order to minimize it. SETTING: In vitro study, connecting several commercially available mechanical ventilators, with different settings, to an active model lung, developed in our department. METHODS: Gas flow and volume, and airway pressure were measured and digitally recorded; Wex was computed by pressure-volume loops. The maximum negative pressure attained in the circuit (delta Pmax), before the endotracheal tube, the time necessary to reach such a pressure [t(delta Pmax)], from the start of the model lung inspiration, and the time to return to atmospheric pressure [t(P = 0)] after mechanical ventilator activation were also recorded. Different inspiratory flow waveforms (sinusoidal, square and inverted ramp) were tested. RESULTS: Wex was not different between ventilators. However, it was significantly (F8,24 = 2.697, p < 0.05) affected by different flow waveforms: Wex was markedly higher (p < 0.01) with sinusoidal (16.50 +/- 12.12 mJ) than with either square (1.17 +/- 0.96 mJ) or inverted ramp (0.60 +/- 0.70 mJ) inspiratory flow curve. Furthermore, Wex was significantly correlated (p < 0.001) with delta Pmax, t(delta Pmax) and t(p = 0). Those variables are dependent, although not uniquely, upon the trigger mechanism's sensitivity and the ventilator's response time; thus, Wex can be loosely correlated to them as well. CONCLUSIONS: Since AMV is targeted at farily critical patients, whose oxygen consumption might be marginal, every excess work has to be minimized, in order to avoid respiratory fatigue appearance, and worsening of respiratory failure. Prerequisites of a correct AMV application are thus sensitive trigger mechanism, rapid ventilator response to patient's inspiratory effort, and high initial inspiratory flow (inverted ramp or square waveform).

The compliance of hypocaloric diet in type 2 diabetic obese patients: a brief-term study.

In studies of the effect of diets in obese type 2 diabetic patients, information about the degree of compliance or non-compliance is generally lacking or incomplete, though their poor long-term success rate is widely recognized. We have quantified the degree of short-term compliance with a personalized hypocaloric diet (800-1500 kcal) in 77 obese type 2 diabetic patients (mean age 60, mean BMI 34.4) three months after explaining their dietary schedule and its expected advantages by means of simple but essential nutritional advice lasting about 20 minutes of the type currently used for such patients attending diabetes care institutions or outpatient departments. Even though a mean 14% reduction in daily food intake was achieved, the mean daily energy intake at the interview (assessed by means of the 3-day recall method) still exceeded the prescribed diet by 40-50%. The worst compliance in terms of total excess energy intake or carbohydrate and fat intake was found in the older patients. The greater the excess of food intake, the poorer the metabolic control, as expected.