Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

AIMS: This study measured the insulin concentration (Ins[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). METHODS: Measurements included Ins[C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. RESULTS: In vials of NPH(R+) (assumed to be 100%), Ins[C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively. Likewise, in pen cartridges, Ins[C] in the clear phase of NPH(R-) was<1%, but 182±33%, 204±22% and 229±62% in the cloudy phases of Novo, Lilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). CONCLUSION: Ins[C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension.

Correlation between maternal body composition and haemodynamic changes in pregnancy: different profiles for different hypertensive disorders.

OBJECTIVES: To assess and correlate changes in body composition and haemodynamic function during pregnancy. To identify different haemodynamic profiles based on the onset of hypertensive diseases such as gestational hypertension and preeclampsia. METHODS: We enrolled 265 healthy, normotensive pregnant women throughout pregnancy (from 6+0 to 36+0weeks). They were subjected to assessment of body composition and haemodynamic function using non-invasive methods. We divided our population in three groups: group A with physiological pregnancy, group B with gestational hypertension and group C with preeclamptic patients. RESULTS: In patients who developed gestational hypertension we found lower total body water (TBW) percentage, higher Fat Mass (FM), associated with lower Cardiac Output (CO) and higher Total Vascular Resistance (TVR) during the second trimester. In the third trimester we didn't find haemodynamic differences, but a significative increase in extracellular water (ECW) percentage. In patients who developed preeclampsia we found since the first trimester significative higher TVR and hypodynamic circulation, associated with lower FM percentage. CONCLUSIONS: Assessment of body composition and maternal cardiac function may help to identify earlier in pregnancy, patients with different (mal) adaptations to pregnancy. Women with high TVR, hypodynamic circulation and low fat mass during the first trimester, might be at higher risk to develop preeclampsia. Patients with higher BMI and FM percentage, and increased TVR in the second trimester, might be at risk of gestational hypertension and excessive fluid retention at the end of pregnancy.

Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients.

OBJECTIVE: To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). METHODS: One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. RESULTS: One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. CONCLUSIONS: Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Questionnaire-based evaluation of occupational and non-occupational solar radiation exposure in a sample of Italian patients treated for actinic keratosis and other non-melanoma skin cancers.

BACKGROUND: An adequate evaluation of the ultraviolet (UV) cumulative exposure is a major problem in epidemiological studies on chronic skin damage. Questionnaires may be applied as useful tools. OBJECTIVE: We developed an original questionnaire to evaluate individual cumulative exposure to solar radiation (SR) in patients affected by actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHOD: The questionnaire, considering both working and leisure exposure, was applied to evaluate the whole life history of solar UV radiation exposure in a group of patients of the Dermatologic Clinic of UNIMORE. RESULTS: In outdoor workers (OW), the co-presence of AK/in situ SCC and invasive non-melanoma skin cancers (NMSCs) was increased compared to indoor workers (IW), as was the frequency of multiple skin lesions. The prevalence of skin lesions of the face was significantly higher in OW. Work 'sometimes' or 'often' in the shades was associated with an absence of skin lesions on the shoulders and neck, while workers adopting 'sometimes' or 'often' a downward bent position were more likely to develop lesions on the top of the head. Considering leisure activities, the use of tanning beds was associated to the presence of skin lesions on the shoulders, neck and chest. Considering vacation periods, subjects spending at least 2 h outdoor in the period 11 am to 1 pm presented earlier diagnoses of skin cancers. CONCLUSION: Results of the original questionnaire developed are coherent with current knowledge and confirm the important role of UV exposure, both occupational and recreational, in the development of AK and NMSCs. Data support the hypothesis that this questionnaire can be applied as useful tool for the evaluation of cumulative UV exposure in future epidemiological studies.

Disappointed Love and Suicide: A Randomized Controlled Trial of "Abandonment Psychotherapy" Among Borderline Patients.

To determine whether ambulatory psychotherapy targeted to abandonment experiences and fears can reduce suicidality and improve outcome in borderline patients referred to the emergency room with major depressive disorder and self-destructive behavior severe enough to require medical/surgical treatment and a brief psychiatric hospitalization. A total of 170 subjects were randomized at hospital discharge into three treatment groups: treatment as usual (TAU), abandonment psychotherapy delivered by certified psychotherapists, and abandonment psychotherapy delivered by nurses. Assessments were performed before randomization and at 3-month follow-up. Continued suicidality and other outcome measures were significantly worse in the treatment-as-usual as compared to both abandonment psychotherapy groups, but there were no differences between the two psychotherapy groups. These results suggest the efficacy of manualized psychotherapy that specifically targets the abandonment fears and experiences that are so common as precipitants to suicidal and self-destructive acts in borderline patients. It does not appear that formal psychotherapy training is associated with better outcomes.

Assessment of total vascular resistance and total body water in normotensive women during the first trimester of pregnancy. A key for the prevention of preeclampsia.

INTRODUCTION: Maternal cardiovascular system adapts to pregnancy, thanks to complex physiological mechanisms that involve cardiac output, total vascular resistance and water body distribution. Abnormalities of these adaptive mechanisms are connected with hypertensive disorders. OBJECTIVE: To identify patients at a high risk of developing hypertensive complications of pregnancy during the first trimester of pregnancy, through the use of non-invasive methods such as USCOM (Ultrasonic Cardiac Output Monitor) and Bioimpedance. MATERIALS AND METHODS: We enrolled 120 healthy normotensive women during the first trimester of pregnancy obtaining all measurements with the USCOM system and Bioimpedance. RESULTS: 20 patients were excluded for a bad USCOM signal. The remaining patients (n = 100) were retrospectively divided into two groups: Group A (n = 75) TVR<1200 dynes s cm(-5), Group B (n = 25) TVR>1200 dynes s cm(-5). No statistically significant difference was identified in terms of water distribution, Fat Free Mass, Systolic/Diastolic Blood Pressure, Heart Rate, Hematocrit, Flow Time Corrected and Water Balance Index between the two groups. In contrast, higher values of the Cardiac Output, Stroke Volume, Fat Mass and Inotropy Index have been highlighted in the Group A. Moreover, in the Group A we found a better maternal-neonatal outcome and a lower incidence of hypertensive complications. CONCLUSIONS: High TVR during the first weeks of gestation may be an early marker of cardiovascular maladaptation more than the evaluation of water distribution and, in particular, with respect to the single blood pressure assessment. Moreover lower values of Inotropy Index could be an indicative of the worst cardiac performance.

[Urticarial vasculitis associated with essential thrombocythaemia progressing to myelofibrosis]. / Vascularite urticarienne associée à une thrombocytémie essentielle avec myélofibrose secondaire.

BACKGROUND: Urticarial vasculitis (UV) is a rare form of leukocytoclastic vasculitis in which skin lesions resemble urticaria. UV comprises hypocomplementemic and normocomplementemic subtypes. To date, only 4 cases of UV associated with myeloproliferative disorders have been described, including 3 cases with essential thrombocythaemia (ET) and one case with polycythaemia vera. PATIENTS AND METHODS: We describe the case of a 59-year-old male patient with JAK2-positive TE and secondary myelofibrosis and who developed multiple urticarial papules persisting for more than 24hours. Skin biopsy showed perivascular neutrophilic infiltrate with margination of neutrophils in the lumen of vessels and some leukocytoclastic patterns, and with red cell extravasation consistent with UV. Treatment with ruxolitinib (a JAK2 inhibitor) induced transient and partial control of the haematological symptoms but did not prevent UV flare. Prednisolone 20mg once daily was added, with good clinical response. DISCUSSION AND CONCLUSION: To our knowledge, this is the fourth reported case of UV associated with ET and the first case associated with MF.

Ribosomal protein S6 is hyperactivated and differentially phosphorylated in epidermal lesions of patients with psoriasis and atopic dermatitis.

BACKGROUND: The ribosomal protein S6 is part of the translation machinery and is activated by phosphorylation via the mammalian target of rapamycin pathway, which is activated in psoriatic skin. OBJECTIVES: To investigate which S6 sites are phosphorylated in psoriasis and atopic dermatitis (AD), and to study whether S6 phosphorylation is associated with inflammation and/or keratinocyte hyperproliferation. METHODS: Healthy skin and skin lesions of patients with psoriasis and AD were investigated by immunostaining using antibodies that stain proliferating cells, leucocytes and distinct phosphorylated sites of S6. RESULTS: All psoriasis and AD lesions revealed abnormal S6 phosphorylation in the epidermis. The extent of S6 phosphorylation was diverse, generally stronger in psoriasis and correlated, in both diseases, with inflammation. S6 showed differential phosphorylation in distinct epidermal layers, which was most pronounced in hyperproliferative regions. CONCLUSIONS: Differential S6 phosphorylation may have a role in abnormal keratinocyte proliferation/differentiation.

The ALPPS procedure for hepatocellular carcinoma.

BACKGROUND: The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. METHODS: ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. RESULTS: The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. CONCLUSIONS: This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.

Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: a dose-response study.

BACKGROUND AND AIMS: After subcutaneous injection insulin glargine is rapidly metabolized to M1 and M2. In vitro, both M1 and M2 have metabolic effects and bind to IGF-1R similarly to human insulin, whereas glargine exhibits a higher affinity for the IGF-1R and greater mitogenetic effects. The present study was specifically designed to establish the dose-response metabolism of glargine over 24 h following s.c. injection in T2DM subjects on long-term use of glargine. METHODS AND RESULTS: Ten subjects with T2DM were studied during 24 h after s.c. injection of 0.4 (therapeutic) and 0.8 (high dose) U/kg of glargine on two separate occasions during euglycaemic clamps (cross-over design). Glargine, M1 and M2 over 24 h period were determined in appropriately processed plasma samples by a specific liquid chromatography-tandem mass spectrometry assay. Plasma M1 concentration (AUC0-24 h) was detected in all subjects and increased by increasing the glargine dose from therapeutic to high dose (p = 0.008). Glargine was detectable in 6 (therapeutic dose) and 9 (high dose) out of the 10 subjects and also increased by increasing the dose (p = 0.031). However, glargine concentration (AUC0-24 h--high dose) represented at most only 9.7% (4.6-15%) of the total amount of insulin measured in the blood. M2 was not detected at all. CONCLUSION: In T2DM people on long-term use of insulin glargine, even with higher doses (0.8 U/kg), glargine is nearly totally metabolized to the active metabolite M1. Glargine is often detectable in plasma, but its concentration remains well below that needed in vitro to potentiate IGF-1R binding and mitogenesis.

Long-term effect of exercise on bone mineral density and body composition in post-menopausal ex-elite athletes: a retrospective study.

OBJECTIVES: The aim of this retrospective study was to determine the long-term effect of exercise on bone mineral density (BMD), bone mineral content (BMC) and body composition (BC) in post-menopausal women who were elite athletes during their youth compared with sedentary controls. SUBJECTS/METHODS: It is a retrospective study and carried out in an outpatient clinic. A total of 48 post-menopausal women (54-73 years of age) were enrolled. Ex-elite athletes with long-term (>20 years) histories of significant training and performance were divided into two groups: weight-bearing sports (runners, n=12) and non-weight-bearing sports (swimmers, n=12). The athletes were age matched with sedentary controls (n=24). BMD, BMC and BC were measured using dual-energy X-ray absorptiometry. Healthcare and sport activity histories were evaluated using a questionnaire. RESULTS: No significant differences were found with regard to body weight, height, body mass index and hours of activity between the two groups of athletes. There were no significant differences in activity levels between athletes and controls at the time of this study. BMD and BMC were not significantly different between athletes; they were significantly higher in athletes than in controls (P<0.001). Although the ex-athletes did not significantly differ in BC, left and right lean arm mass and arm BMD were significantly higher in swimmers than in runners (P<0.0001). CONCLUSIONS: The high level of physical activity observed in female athletes is associated with improved muscle mass, BMD and BMC, and physical activity during youth seems to have a beneficial effect on bone mass and helps to prevent bone loss due to aging.

New trends in nutritional status assessment of cancer patients.

BACKGROUND: Nutritional status assessment and support should be considered a valuable measure within the overall oncology strategy. Despite extensive research in the field of clinical nutrition, definite guidelines to base rational nutritional assessment and support in cancer patients are still debated. This review examines different approaches to nutritional status in cancer patients. DESIGN: The assessment of nutritional status is usually based on anthropometric measures, biochemical or laboratory tests, clinical indicators and dietary assessment. At present, body composition (BC) is rarely measured in the clinical setting because it is thought to be too unmanageable and time-consuming. However, using new technologies, the estimation of fat, lean and body fluids, that is significant in the management of nutrition therapies in oncology, has become easy. The present study evaluates the different methods of nutrition assessment today available, especially body composition (BC) measurements. Furthermore, nutrition assessment, relevance of nutritional support and choice of nutritional strategy, in surgical patients, are discussed. DISCUSSION: Given the clinical relevance of nutritional intervention in patients' quality of life, the nutritional status assessment has a key role in oncological and surgical practice and should include BC assessment in order to tailor nutritional treatment to patients' individual requirements. Furthermore, administration of the supplemented diet before and after surgery seemed to be the best strategy to reduce complications and length of hospital stay.

Relationship between body composition, body mass index and bone mineral density in a large population of normal, osteopenic and osteoporotic women.

PURPOSE: The knowledge of factors modulating the behaviour of bone mass is crucial for preventing and treating osteoporotic disease; among these factors, body weight (BW) has been shown to be of primary importance in postmenopausal women. Nevertheless, the relative effects of body composition indices are still being debated. Our aim was to analyze the relationship between body mass index (BMI), fat and lean mass and bone mineral density (BMD) in a large population of women. Moreover, this study represents a first important report on reference standard values for body composition in Italian women. MATERIALS AND METHODS: Between 2005 and 2008, weight and height of 6,249 Italian women (aged 30-80 years) were measured and BMI was calculated; furthermore BMD, bone mineral content, fat and lean mass were measured by dual-energy X-ray absorptiometry. Individuals were divided into five groups by decades (group 1, 30.0-39.9; group 2, 40.0-49.9; group 3, 50.0-59.9; group 4, 60.0-69.9; group 5, 70.0-79.9). Differences among decades for all variables were calculated using a one-way analysis of variance (ANOVA) and Bonferroni test by the SPSS programme. RESULTS: Mean BW was 66.8±12.1 kg, mean height 159.1±6.3 cm and mean BMI 26.4±4.7 kg/m(2). According to BW and BMI, there was an increase of obesity with age, especially in women older than 50 years (p<0.001). Lean mass increased until 50 years of age but significantly decreased after this age (p<0.001). The percentage of osteopenia and osteoporosis in the examined population was 43.0% and 16.7%, respectively. CONCLUSIONS: Our data show that obesity significantly decreased the risk for osteoporosis but did not decrease the risk for osteopenia. It is strongly recommended that a strong policy regarding prevention of osteopenia and osteoporosis be commenced. An overall examination of our results suggests that both fat and lean body mass can influence bone mass and that their relative effect on bone could be modulated by their absolute amount and ratio to total BW.

[Borderline personality disorder is easy to treat: are we ready to accept this good news?]. / Le trouble de la personnalité borderline est facile à traiter: sommes-nous prêts à relever le défi?

Recent research indicated that the outcome of borderline patients is better than previously reported. We assessed the impact of co-morbid personality disorders (PD) on response to treatment and 1-year outcome among 206 borderline patients assigned to crisis intervention program. An overwhelming majority (89%) of borderline patients without supplementary Axis 11 psychopathology exhibited good to very good treatment response at acute treatment discharge as well as good to very good global outcome at 1-year followup (85%). Borderline patients meeting criteria for paranoid, schizotypal, antisocial, narcissistic and dependant personality disorder showed, contrarily, significantly more treatment failures.

[Reasons I liked DSM: the challenge of medical diagnosis in psychiatry]. / Pourquoi j'aimais le DSM: les défis du diagnostic médical en psychiatrie.

The first draft of the fifth version of the American Diagnostic and Statistical Manual (DSM-V) provides an opportunity to clarify the several issues associated with the debate on diagnostic process in psychiatry. Several peculiar aspects of the DSM approach showed stability over time suggesting that this project is rooted in an original conception of mental disease, innovative epistemology of medical judgement and empirically grounded choice of diagnostic categories. Attention will be paid to reasons for actual reject of this clinical philosophy in the US and long-lasting misunderstanding in French speaking countries.

[Medea syndrome: the sadistic fate of impaired mourning of love]. / Le syndrome de Médée, parcours sadique de la perte d'amour.

This work investigated the Medea syndrome, an harassment behaviour endorsed from a spouse suppressing access to children from his partner. The Medea myth adds a psychopathological background to the Parental Children Alienation construct focusing on using children to inflict a revenge, sadistic mourning of love, return of sacrificial rites associated with realm of primitive superego figures among people with severe personality disorder confronting traumatic love. The clinical, diagnostic and legal aspects of the disorder will be presented as well as a range of treatment strategies allowing valuable medical decision. Overall, the Medea syndrome appears to be an extremely destructive reaction with major negative impact on both children and adults. New law roles should be introduced to discourage such behaviour and improve victims protection.

[Expansion of the sphere of crisis: the question of the intrusiveness of the disease]. / Extension du domaine de la crise: la question de l'intrusion de la maladie.

The passage to ambulatory care of a patient with a long hospital stay due to a wrenching disease is not something obvious. The doctor and the care staff will have to take up the challenge of dealing with an important amount of care. The quality of life of the patient and his caregivers is influenced by the neuropsychiatric disorders, the illness intrusiveness and the depression that come along with them. The chronic disease intruding causes a crisis in their lives. In order to better evaluate these factors we are using the Illness Intrusiveness Rating Scale developed by Devins. This article addresses the high complexity of clinical situations handled in an environment of rehabilitation care with the support of the consultants, nurses and doctors, of the liaison psychiatry.

[Chronic pain and depression]. / Douleurs chroniques et dépression: un aller-retour?

Chronic pain and depression are frequently associated. Links between them are numerous and well documented. It is known for example that depression is associated with a greater number and higher intensity of pain symptoms. Similarly the presence of pain complicates the diagnostic evaluation and aggravates the prognosis of depression. The question of the causality link has no clear answer. Taking care of these patients implies to acknowledge the different aspects of their suffering in a holistic bio-psycho-social model. Treatment or medication, for instance antidepressants, should be a post-scriptum to the construction of a therapeutic relationship.