[The role of hyponatremia in the rapid onset of coma after Cyclophosphamide]. / Rôle de l'hyponatrémie dans la survenue rapide d'un coma après Cyclophosphamide.

INTRODUCTION: Cyclophosphamide is an alkylating agent used in routine pulmonary practice, particularly in the management of connectivitis-related diffuse interstitial lung disease. Common side effects are gastrointestinal disorders and immunosuppression, and a sudden and exceptional adverse effect is severe hyponatremia. OBSERVATION: A 78-year-old female patient treated for NSIP-OP in the context of an anti-synthetase syndrome was treated with Cyclophosphamide 15mg/kg. Twenty-four hours after the end of the infusion, she was diagnosed at home in a coma with comitial seizures. Biological assessment revealed severe hyponatremia at 109 mmol/l with blood hypo-osmolarity. The patient's condition rapidly improved following correction of the ionic disorder. CONCLUSION: Hyponatremia induced by low-dose Cyclophosphamide is a rare but serious adverse effect that requires special attention.

[Emphysema, did you say emphysema?] / Emphysème, vous avez dit emphysème ?

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common condition that may initially look simple but may conceal other diseases capable of accelerating its natural history or even simulating it. We describe four cases presenting as COPD with emphysema that were reclassified on the basis of certain clinical characteristics and the radiological pattern. CASE REPORTS: A 52 year old never smoking woman presenting with emphysema was eventually diagnosed as having lymphangioleiomyomatosis on the basis of an abdominal CT scan showing kidney angiomyolipomas. A 44 years old smoker presenting with rapidly evolving emphysema was eventually diagnosed as having Langerhans cell histiocytosis on the basis of a previous chest CT (four years earlier) showing cavitating nodules. An airport refueler, 73 years old, with severe emphysema despite never having smoked, was eventually diagnosed as suffering from alpha-1 antitrypsin deficiency. The last patient was a 54 year old man, a never smoker, who presented with severe airflow limitation and multilobar hyperlucency, with bronchiectasis in the same areas. He was eventually diagnosed as having a severe form of the Swyer-James-MacLeod syndrome. CONCLUSION: These four case reports underline the importance of questioning the diagnosis of COPD when certain particular phenotypic characteristics are identified.

Pulmonary sarcoid-like granulomatosis induced by nivolumab.

The use of antibodies against programmed death (PD)1, such as nivolumab and pembrolizumab, has dramatically improved the prognosis of patients with advanced melanoma. Nivolumab is also approved in advanced squamous cell nonsmall-cell lung cancer. These immunotherapies are associated with a unique set of toxicities termed immune-related adverse events, which are different from toxicities observed with conventional cytotoxic chemotherapy. We report the case of a 56-year-old man who was diagnosed with metastatic melanoma and who received nivolumab. One week after the second infusion, he developed pulmonary symptoms, dry eye syndrome and a bilateral swelling of the parotid glands. Investigations were negative for infection. The bronchoalveolar lavage differential cell count showed 32% lymphocytes with an increased CD4 : CD8 ratio, and bronchial biopsies revealed noncaseating epithelioid granulomas, without malignant cells. The clinical and radiological courses were rapidly favourable with oral corticosteroid. This case illustrates that sarcoidosis can be induced by nivolumab treatment. With the increasing use of anti-PD1 inhibitors in patients with advanced melanoma and squamous cell nonsmall-cell lung cancer, clinicians should be aware of this potential associated immune-related adverse event.

Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.

Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C) + roxithromycin (RX) or AMX + ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p > 0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p < 0.001. An unfavorable outcome was less frequent in group 1: 5.4 % vs. 9.9 %, p = 0.001. In logistic regression models, concordant therapy was associated with a favorable outcome: adjusted odds ratio (AOR) [95 % confidence interval (CI)] 1.85 [1.20-2.88], p = 0.005. CAP therapy without RFQ and Ceph-3 use was associated with a shorter LOS and fewer unfavorable outcomes.

Occupational therapy and dementia: the experience of an Alzheimer special care unit.

This trial reports the outcomes of an occupational therapy (OT) program in a group of patients with moderately severe dementia, attending a day care center. Twenty-six patients were enrolled in this therapeutic program for a 12-month period. OT sessions were held for two hour a day, five days a week. The outcomes of the trial suggest that the introduction of OT and multidimensional assessment may improve management and mediate the psychophysical decline of persons with dementia. Indeed, the assessed performance indices remained relatively stable over time, as compared to the decline expected by the natural progression of disease. Moreover, behavioral disorders evaluated by the neuropsychiatric inventory (NPI) scores improved appreciably between treatment start and end. The day care center provides an opportunity for both the person with dementia and their family by optimizing therapy for the patient and providing medical assistance for morbid conditions that ensue during the course of disease and by lowering the burden of care and providing moral support for the family by a trained staff, with particular focus on behavioral disorders that are not amenable to pharmacological management.

Histological study on sinus lift grafting by Fisiograft and Bio-Oss.

The work aims to provide a histological investigation of Fisiograft, a PLA/PGA copolymer, used as filler for bone defects in humans. The study was performed on biopsies of sinus lifts where Bio-Oss and Fisiograft gel were applied as graft material. Bone regeneration was satisfactory in all sinus lifts, even when Fisiograft was applied alone. Due to remarkable osteoclast activity, Bio-Oss granules were cleared from the majority of biopsy cores. At histology, Fisiograft gel appeared as globes enveloped by fibroblasts, displaying an epithelial-like cell appearance. Due to its solubility in solvents, undegraded Fisiograft (recorded for 7 months or more) did not stain whereas degraded Fisiograft stained positive. The loose connective tissue, that surrounded Fisiograft and bone contained isolated mastocytes. Bone grew inside the loose connective and often reached the surface of Fisiograft by intervening cells. The results seem to indicate that Fisiograft may be considered both a polymer useful for fastening bone substitutes inside a defect and in addition a material capable of prompting bone regeneration, with or without the use of a bone substitute. In addition to space-former and space-maintainer functions, Fisiograft shows potential bone stimulation function, which may be labelled as osteopromotive capability.

Release of elements from retrieved maxillofacial plates and screws.

Vitallium appliances and surrounding tissues were investigated to evaluate the release and accumulation of elements. Four microplates, sixteen screws and surrounding tissues were removed from three patients presenting inflammation 4 to 6 years after surgery and were submitted to SEM and X-ray microprobe analysis. Histology was performed on paraffin or PMMA sections of tissues.A continuous release of elements from metallic appliances into soft tissues was observed. Cobalt, chromium, and nickel were detected in soft and boney tissues in close proximity to the appliance. Aluminium, as a component of screw coatings, accumulated in soft tissues, and a remarkable amount of aluminium was detected in the dense lamella of lamellar bone. The results suggest that coatings containing aluminium should be avoided and the time these appliances are allowed to remain in patients should be shortened. Further studies on element release and the fate of aluminium in bone are warranted.

As novas tecnologias telemáticas na rede dos serviços sociosanitários / Telemedicine in sociomedical care networking

A telemedicina é um campo de conhecimento emergente na relaçäo médico-paciente e na organizaçäo do sistema sanitário em geral; possui tecnologias para pesquisa clínica à distância e para a obtençäo das condiçöes pessoais e ambientais a partir de um centro de esculta e controle, colocado em uma sede distante em relaçäo ao paciente. Os idosos com perda das habilidades, frágeis e portadores de enfermidades obtém muitas vantagens com a Telemedicina, porque podem aderir com facilidade aos serviços sociais e sanitários dos quais säo frequentemente excluídos pela impossibilidade de acessá-los (por inabilidade), pelos excessivos custos, o tempo dispendido. O Centro de Avaliaçäo Geriátrica da Universidade de Modena - Itália, em colaboraçäo com os médicos de família e os administradores locais, ativaram um programa de Telemedicina no âmbito da assistência domiciliar integrada, com o intuito de avaliar a aceitaçäo, a influência no consumo social e sanitário (internaçäo hospitalar, institucionalizaçäo) sobre a mortalidade e a auto-suficiência

Experimental ischemic liver injury and regeneration over 3 months: histological observations in the rat.

Liver histopathology of segmental portal ischemia occurring over a long-term period has not been previously described. For these reasons histological changes in the rat liver were studied from 1 h to up to 90 days after a left lateral and middle segmental portal obstruction. Within 3 h, the hepatocytes showed glycogen depletion in Rappaport zones 1 and 2 and pericentral and central lobular congestion of sinusoids and veins, whereas within 3 days, vein thrombosis appeared in the center of the lobule and liver necrosis was observed in Rappaport zones 2 or 3 or both, followed by restitutio ad integrum of the liver lobule morphology after 20-40 days. These results can be explained in light of two conditions occurring in the rat liver: (i) the peculiar low sensitivity of the liver to O2 debit and the protective or vasoactive effects used during hypoxia; and (ii) the sinusoidal network as a collateral source of the hepatic vascular system. Therefore, morphological assessment of this arteriolar and sinusoidal system, implicated in assuring efficient collateral blood supply in the rat liver with portal ischemia, is essential for understanding the mechanisms behind a natural and timely repair of ischemic injuries in the human liver.

Treatment of postprandial hypotension in the elderly.

Food intake induces splanchnic vasodilation lasting for at least one hour, which can precipitate in postprandial hypotension, if systolic arterial blood pressure falls by more than 20 mmHg. Postprandial hypotension has a high prevalence in the elderly, above all in subjects receiving hypotensive drugs or in those with disorders of the autonomic nervous system. In our total case series of 567 subjects, the prevalence of postprandial hypotension evaluated by 24-hr blood pressure recording, was 14.5%, increasing to 28% in the oldest group. Since relevant cerebral ischemic symptoms may become manifest, a correct diagnosis of the disorder and both pharmacological and non-pharmacological therapeutical approaches are of great importance for the wellbeing of old patients.

Prospective population survey: do centenarians change?

Two groups of centenarians (32 subjects) were evaluated, residing in the same geographic area, in two sampling periods (1988 and 1992). The characteristics of the groups were compared to see how this age class changed over a 4 year period. Significant differences were found for the number of centenarians, their level of dependency and the use of drugs.

A survey of a centenarian population in Italy, focusing on self-sufficiency and cognition.

Eighty-six persons aged 100 years or older (20 males and 66 females) living in urban areas of different Italian regions were examined between 1985 and 1992, aimed at describing the characteristics of centenarians in an entire population. The female/male ratio was 4 to 1, and 69% of the centenarians lived at home. Body mass index was 21.3 in females and 24.5 in males. The subjects typically reported no major diseases, only a few hospital admittances (1.2/lifetime) and a limited use of regular medication (on average: 1.4 drugs). The mothers and fathers of the centenarians lived 76.2 and 74.2 years, respectively. The Activities of Daily Living scale revealed a decrease in instrumental activities, and an adequate self-maintenance in the majority of centenarians; a full score on the Physical Self Maintenance Scale was reached by 10% of the subjects; these scores were not significantly influenced by the isolated sensory deficits but were lower in patients with multiple impairments. The Mini Mental State Examination score was overall 17.7 +/- 8.3 for the group, reaching 24.1 in male and 20.2 in female literate subjects without major hearing or vision defects; these scores varied significantly in relation to sensory deficits and education. In our centenarian population males reached extreme old age less frequently, but with a better quality of life, than females. The good overall performance of the whole population, and especially of the subpopulation without impairments, suggests a selective survival of centenarians, as also demonstrated by the long lifespan of their immediate relatives.

Hormone levels in centenarians.

The serum profiles of total triiodothyronine (T(3)), free thyroxin (fT(4)), thyroid stimulating hormone (TSH), cortisol, prolactin (HPRL), parathormone (PTH), osteocalcin and growth hormone (GH) were measured in a group of 12 centenarians and compared to the values of a control group of twenty-nine subjects, aged 67-98 years. The study was aimed at revealing whether there are appreciable differences or age-related modifications in the hormone status of healthy control elderly and the centenarian population. In this series, the modifications in hormone levels were unremarkable, and the serum levels of the studied hormones in centenarians often fell within a range considered to be normal for the younger age classes.

Prevention and therapy of fractures in the elderly: costs and benefits.

Costs for health care, nursing and rehabilitation of bone fractures in the elderly, in particular, of fractures of the femur, are in continuous increase. The allocation of financial resources for their prevention have to take into account the costs and benefits of both drug and non-pharmacological treatments, which should be validated through experimental trials based on valid endpoints. These preventive measures must be applied to the population at highest risk of fracture, in particular, in women older than 60 years of age.

Influence of a double blind pharmacological trial on two domains of well-being in subjects with age associated memory impairment.

This random double-blind trial compares psychological well-being and perceived quality of life in 60 subjects (18 M, 42 F), mean age 61 years, with age-associated memory impairment (AAMI), who were administered a standardised ginseng-containing vitamin complex or placebo for 9 months. We evaluated psychological well-being, in terms of affective status and memory functioning using the Symptom Rating Test [SRT] (depression, anxiety, somatisation, inadequacy) and Randt Memory Test [RMT] (memory index [MI]), respectively, and the quality of life, using the Life Satisfaction in the Elderly Scale [LSES]. At final evaluation, SRT did not differ in the drug and placebo groups, whereas MI and LSES were significantly higher in the drug-treated group. Moreover, the negative correlation between the affective (SRT) and cognitive (MI) component of psychological well-being waned in the drug-treated but not placebo group. In the drug-treated group, a positive correlation emerged between the cognitive index and social contacts, mood and self-concept factors of the LSES. In both groups, the initial negative correlations between quality of life (LSES) and affection (SRT) persisted at the end of the study. Drug-treated AAMI subjects differ from controls in part by improved scores on objective cognitive tests but even more so by modifications of the correlations among indexes of psychological well-being and quality of life.

Improvement of ursodeoxycholic acid bioavailability by 2-hydroxypropyl-beta-cyclodextrin complexation in healthy volunteers.

Tablets containing the inclusion complex of ursodeoxycholic acid (UDCA) with 2-hydroxypropyl-beta-cyclodextrin were prepared by direct compression. Plasma concentrations of UDCA were determined in six healthy volunteers after oral administration of tablets containing the inclusion complex or UDCA alone (Ursacol). Following the administration of the complex tablets, the mean area under the plasma concentration curve (AUC) and the maximum UDCA plasma concentration (Cmax) were significantly higher than those obtained after the administration of the commercial ones. Moreover, the time of maximum plasma concentration (tmax) appeared at a shorter time. These results may be explained by the increase of the UDCA dissolution rate via complex formation.

Different resistance of mammalian red blood cells to hemolysis by bile salts.

To evaluate why hemolysis of red blood cells (RBC) by bile acids varies in different mammalian species, we determined the mean corpuscular volume (MCV), lipid content and the concentrations of the conjugates of deoxycholate and of NaCl inducing 50% hemolysis of RBC from healthy humans, pigs, horses, cows, sheep and jaundiced humans. A volume of 0.05 mL of washed RBC at 1% hematocrit, which has the same lipid content but different phospholipid composition and number of erythrocytes (owing to the variable MCV), was incubated in taurodeoxycholate (TDC) solution (0-5 mM) to determine the TDC concentration inducing 50% hemolysis (TDC50). The TDC50 was highest in RBC of sheep and decreased within the series sheep > pig > cow > horse > healthy human > jaundiced human, which have generally increasing MCV. The osmotic resistance followed an inverse order, with jaundiced human > healthy human > horse > cow > pig > sheep. Although we found no correlation between the TDC50 and phospholipid composition of the erythrocytes tested, the extent of bile salt-induced hemolysis seemed to depend on both the MCV and the number of erythrocytes in the incubation medium.

Urinary excretion of bile acids during acute administration in man.

Six healthy subjects, 45-72 years old, received a 10-day feeding of 750 mg of two of the following bile acids: deoxycholate (DCA), chenodeoxycholate (CDCA), cholate (CA), hyodeoxycholate (HDCA), ursodeoxycholate (UDCA), and ursocholate (UCA). The urinary excretion of total bile acids was low during administration of lipophilic bile acids (DCA and CDCA), when serum levels show low postabsorption peaks. Instead, hydrophilic bile acids (UDCA and above all HDCA) were heavily excreted in the urine as sulphates and glucuronides, and serum levels reach high values. Only UCA, strongly hydrophilic, was predominantly excreted as unconjugated fractions. Thus, the physicochemical properties of bile acids (as measured by both the partition between octanol and water, and the water solubility) were factors that influenced the route of bile acid elimination from the body, whereas their conjugation was not always requested for urinary excretion.