Primary cutaneous interdigitating dendritic cell sarcoma (IDCS): Report of a new case and literature review.

Interdigitating dendritic cell sarcoma is a very rare entity in the spectrum of histiocytic and dendritic cell neoplasms that mostly occurs in lymph nodes, generally presenting as solitary lymphadenopathy, but may affect every organ. Among extra nodal sites, cutaneous interdigitating dendritic cell sarcoma is exceedingly rare; to date, only 9 cases have been described in English literature. The mean age at diagnosis was 60 years, with a male-female ratio of 1,5 to 1; clinically, two different modalities of skin presentation have been reported: solitary, represented by a single red-brownish nodular lesion, or diffuse, characterized by multiple nodular lesions in one or more body districts. The extreme rarity of this sarcoma and its morphological similarity to other poorly differentiated tumors may lead to a delay in diagnosis; in particular, cutaneous localization may be difficult to differentiate from follicular dendritic cell sarcoma, Langerhans cell sarcoma, poorly differentiated squamous cell carcinoma and more generally sarcomatoid carcinoma, atypical fibroxanthoma, malignant melanoma and several sarcomas. Immunohistochemistry plays an important role in identifying this rare entity and formulating a correct histological diagnosis, fundamental requirement for choosing the best therapeutic approach. We report herein a further case of an 81-year-old Caucasian woman who presented to the Dermatology Department to remove an asymptomatic skin papule in the left temporal region, clinically diagnosed as dermatofibroma. The overall pathological and immunohistochemical features supported the diagnosis of a malignant dendritic cell tumor, consistent of interdigitating dendritic cell sarcoma.

A case of dysgraphia induced by sertraline and a review of official spontaneous adverse reaction databases.

WHAT IS KNOWN AND OBJECTIVES: The occurrence of dysgraphia after sertraline intake has never been reported. The objective was to describe a case of this adverse drug reaction and present a review of similar cases held in international databases with a discussion of the possible pharmacological mechanisms. CASE SUMMARY: We observed a 60-year-old man who experienced resting tremors, dyskinesia and dysgraphia 2 months after a stepwise increase in sertraline dosing from 50 to 200 mg/day. WHAT IS NEW AND CONCLUSION: Dysgraphia is a possible adverse drug reaction to sertraline, and we suggest that inhibition of extrapyramidal dopaminergic activity might be the pharmacological mechanism.

Imaging techniques and combined medical and surgical treatment of perianal Crohn's disease.

Crohn's disease is a chronic inflammatory disease which may involve any segment of the gastrointestinal tract, most frequently the terminal ileum, the large intestine, and the perianal region. The symptoms of perianal Crohn's disease include skin disorders, hemorrhoids, anal ulcers, anorectal stenosis, perianal abscesses and fistulas, rectovaginal fistulas and carcinoma of the perianal region. The perianal manifestations of Crohn's disease cause great discomfort to the patient and are among the most difficult aspects to treat. Management of perianal disease requires a combination of different imaging modalities and a close cooperation between gastroenterologists and dedicated surgeons.

Variation in the energy and macronutrient contents of texture modified hospital diets / Variación en la energía y contenido de macronutrientes de dietas hospitalarias con textura modfiicada

Objective: To compare the nutritional content of the main meals of a normal hospital diet with those of texture modified diets (soft, puréed and liquid). Methodoloogy: The ash, moisture, macronutrient and energy contents of the foods comprising the main meal of the hospital diets were determined. The values were calculated per capita for each food item comprising the diets and then added up in order to estimate the total amount of energy and macronutrients supplied by main meal. Results: Compared with the normal diet, the puréed and liquid diets presented higher moisture content as well as reduced content of energy (31.4% and 39.9%, respectively), protein (45.4% and 79.8% ,respectively) and lipid (41% and 76%, respectively). Conclusion: Texture modified diets exhibit lower energy and macronutrient content, the main changes being detected for the liquid diet, which might imply an insufficient micronutrient supply.

Objetivo: Comparar la composición nutricional de las comidas principales en la dieta hospitalaria en general con los de las dietas modificadas para la consistencia (blanda, puré y líquida). Metodología: Se determinó el contenido de cenizas, humedad, nutrientes y energía de los alimentos de la comida principal de las dietas hospitalarias recogidas. Los valores fueron convertidos a cantidades per cápita establecidas para cada alimento de cada dieta y sumados con el fin de estimar el total ofrecido por la comida principal. Resultados: Las dietas líquida y puré tuvieron más humedad, reducción de 41 a 76.0% del contenido de grasas, reducción de 45.4 a 79.8% del contenido proteico y de 31.9 a 39.9% de la energía total. Conclusión: Las dietas de consistencia modificada presentaron una reducción en el contenido de energía y macronutrientes, encontrándose los principales cambios en la dieta líquida, lo que culminó en una probable disminución de la ingesta de micronutrientes.

[Complications of leg diaphyseal fracture in a pediatric patient: case report]. / Complicanze di una frattura diafisaria di gamba in un paziente in età pediatrica. Caso clinico.

Fractures in pediatric age have a prominent role when the growth plates are involved, which represent the point of least resistance of the skeleton in children. Traumas in these regions can, therefore, cause chondroepiphysary detachments and alterations of vascularisation which can result in growth anomalies. The aim of this paper is to stress how an early diagnosis combined with a correct therapeutic approach can avoid the onset of deformations and serious disabilities. The case of a 14-year-old boy with an evident deformation and functional impotence of the ankle joint associated with a 7.5 cm heterometry is described. Clinically limping, widespread muscular hypotrophy and a vast zone of trophic suffering of the skin were observed. Anamnesis revealed combined a tibia/fibula fracture due to a trauma caused by crush at the age of 4 years, treated in another hospital by the implant of an intramedullary nail. Upon removal of the nail, relatives referred a progressive deformation of the articulation. Radiographic view showed the presence of an antero-medial epiphysiodesis zone of the distal tibial physis. For this condition the patient underwent a double osteotomy associated with elongation of the same limb by way of Ilizarov external fixator which was removed after 7 months resulting in an evident correction of the axis and the length of the limb. The patient was kept under observation for a follow-up of 2 years with clinical and radiographic controls.

Sensor applications of attenuated total reflection infrared spectroscopy.

Attenuated total reflection Fourier transform infrared spectroscopy is one of the most powerful methods for recording infrared spectra of biological materials in general, and of biological membranes in particular. It is fast, yields a strong signal with only a few micrograms of sample and recent ATR devices allow the recording of nanogram quantities. Importantly, it allows information about the orientation of various parts of the molecules under study to be evaluated in an oriented system. While mid-infrared radiation has been most used for fundamental research on molecular structure, it is becoming an interesting alternative for sensor research. In addition to the usual sensor response, one of its advantages is its sensitivity to molecular conformation. In turn, the binding of a drug onto a receptor may be monitored as for other detection methods but in addition the evaluation of the structural response of the receptor to this binding is likely to bring invaluable information on the mechanism of action of the drug. The present review focuses only on the ATR-mid IR spectroscopy with a special interest for proteins and biological membranes.

Proton motive force mediates a reorientation of the cytosolic domains of the multidrug transporter LmrP.

LmrP from Lactococcus lactis is a 45-kDa membrane protein that confers resistance to a wide variety of lipophilic compounds by acting as a proton motive force-driven efflux pump. This study shows that both the proton motive force and ligand interaction alter the accessibility of cytosolic tryptophan residues to a hydrophilic quencher. The proton motive force mediates an increase of LmrP accessibility toward the external medium and results in higher drug binding. Residues Asp128 and Asp68, from cytosolic loops, are involved in the proton motive force-mediated accessibility change. Ligand binding does not modify the protein accessibility, but the proton motive force-mediated restructuring is prerequisite for a subsequent accessibility change mediated by ligand binding. Asp142 cooperates with other membrane-embedded carboxylic residues to promote a conformational change that increases LmrP accessibility toward the hydrophilic quencher. This drug binding-mediated reorganization may be related to the transition between the high- and low-affinity drug-binding sites and is crucial for drug release in the extracellular medium.

Hydrogen-deuterium exchange in membrane proteins monitored by IR spectroscopy: a new tool to resolve protein structure and dynamics.

As more and more high-resolution structures of proteins become available, the new challenge is the understanding of these small conformational changes that are responsible for protein activity. Specialized difference Fourier transform infrared (FTIR) techniques allow the recording of side-chain modifications or minute secondary structure changes. Yet, large domain movements remain usually unnoticed. FTIR spectroscopy provides a unique opportunity to record (1)H/(2)H exchange kinetics at the level of the amide proton. This approach is extremely sensitive to tertiary structure changes and yields quantitative data on domain/domain interactions. An experimental setup designed for attenuated total reflection and a specific approach for the analysis of the results is described. The study of one membrane protein, the gastric H(+),K(+)-ATPase, demonstrates the usefulness of (1)H/(2)H exchange kinetics for the understanding of the molecular movement related to the catalytic activity.

Detection of structural and functional asymmetries in P-glycoprotein by combining mutagenesis and H/D exchange measurements.

During the last few years, Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR) has become one of the most powerful methods to determine the structure of biological materials and in particular of components of biological membranes, like proteins which cannot be studied by X-ray crystallography and NMR. Indeed, ATR-FTIR method requires little amount of material, gives valuable information about the secondary structure, orientation and tertiary structure changes in peptides and proteins. Moreover, this technique can be used in the presence of lipids and hence provides an excellent tool to study membrane proteins in their natural environment. In this review, we describe how structural information about the catalytic cycle of membrane proteins can be gained by combining ATR-FTIR spectroscopy and mutagenesis. In particular, results obtained about the structure and function of the nucleotide binding domains (NBD) of P-glycoprotein (Pgp), a multidrug transporter involved in cancer cells resistance to chemotherapy, are described.

Delayed infection, late tonsillectomy or adenoidectomy and adult leukaemia: a case-control study.

In a population-based case-control study among adults in Italy, of 261 lymphoid and 313 myeloid leukaemias and 1718 controls, a later age at adenoidectomy and tonsillectomy (after age 10 years) increased considerably the risk of lymphocytic (but not myeloid) leukaemia (odds ratio 4.2, 95% confidence interval 1.1-16.2). We propose that late infection is a proliferative stimulus for B-cells.

Structure and dynamics of the membrane-embedded domain of LmrAinvestigated by coupling polarized ATR-FTIR spectroscopy and (1)H/(2)H exchange.

Bacterial LmrA, an integral membrane protein of Lactococcus lactis, confers multidrug resistance by mediating active extrusion of a wide variety of structurally unrelated compounds. Similar to its eucaryotic homologue P-gp, this protein is a member of the ATP-binding cassette (ABC) superfamily. Different predictive models, based on hydropathy profiles, have been proposed to describe the structure of the ABC transporters in general and of LmrA in particular. We used polarized attenuated total reflection infrared spectroscopy, combined with limited proteolysis, to investigate the secondary structure and the orientation of the transmembrane segments of LmrA. We bring the first experimental evidence that the membrane-embedded domain of LmrA is composed of transmembrane-oriented alpha-helices. Furthermore, a new approach was developed in order to provide information about membrane domain dynamics. Monitoring the infrared linear dichroism spectra in the course of (1)H/(2)H exchange allowed to focus the recording of exchange rates on the membrane-embedded region of the protein only. This approach revealed an unusual structural dynamics, indicating high flexibility in this antibiotic binding and transport region.

Smoking and hematolymphopoietic malignancies.

OBJECTIVE: Tobacco use is the most prominent cause of respiratory cancers. Little is known, however, about the influence of smoking on hematolymphopoietic malignancies. To evaluate this relation, a population-based case-control study was carried out in 12 areas of Italy. METHODS: Detailed interviews on tobacco smoking habits were administered to 1450 non-Hodgkin's lymphoma (NHL), 365 Hodgkin's disease (HD), 270 multiple myeloma (MM), and 649 leukemia (LEU) patients occurring from 1990 to 1993, and 1779 population controls. RESULTS: We found a slightly increased risk for NHL in smokers (odds ratio 1.2, 95% confidence interval 1.0-1.4 for ever smokers), but a consistent positive association was shown only for follicular NHL. In this subtype, a significant excess risk was observed for ever versus never smokers, after adjustment for gender, age, geographic residence, education, and respondent (OR = 1.8, 95%, CI 1.3-2.7), with a positive exposure-response gradient for smoking duration (p < 0.01). The risk for follicular NHL was significantly elevated only among women, with ever smokers showing OR = 2.3 (CI 1.4-3.8), while for men we found OR = 1.3 (CI 0.69-2.3). No major differences were shown according to age. Female subjects also showed significant positive exposure-response trends for duration. CONCLUSION: Cigarette smoking could be a risk factor for follicular NHL among women. For HD, MM, or LEU, no clear association was observed.

A multicenter case-control study in Italy on hematolymphopoietic neoplasms and occupation.

We conducted a population-based, case-control study on hematolymphopoietic malignancies in 12 areas in Italy to investigate associations between different hematolymphopoietic malignancies and exposure to solvents and pesticides. We collected all incident cases 20-74 years of age from 12 areas, with a combined population of approximately 7 million residents. The control group was formed by a random sample of the study population. Data presented in this paper refer to 2,737 interviewed cases of 3,357 eligible cases and to 1,779 of 2,391 eligible controls. We analyzed risks associated with occupation using job-title information to evaluate disease pattern according to job category. An earlier publication presented results for women; here, we report the findings for men and discuss the overall patterns in both genders. The most consistent overall finding was an approximate doubling in relative risk for all four types of malignancies among male managers and related occupations. Several additional occupations were associated with elevated risk of one or more malignancies among men. These included cooks, waiters, and bartenders, and building caretakers and cleaners, for non-Hodgkin's lymphoma; textile workers and machinery fitters for Hodgkin's lymphoma; metal processors, material handlers, rubber workers, and painters for leukemia; and hairdressers, metal processors, tailors, electrical workers, and plumbers for multiple myeloma. The finding of increased risk of non-Hodgkin's lymphoma among both male and female cooks, waiters, and bartenders has not been previously reported; nor has the elevated risk of leukemia among material handlers. Among people engaged in agriculture, those employed as tractor drivers and as "orchard, vineyard, and related tree and shrub workers" appeared to be at increased risk for hematolymphopoietic malignancies.

Delayed infection, family size and malignant lymphomas.

BACKGROUND: The annual incidence of non-Hodgkin's lymphomas (NHL) is increasing by 3%-4% in different parts of the developed world. Excesses of NHL have been observed in populations exposed to immunosuppressants and to HIV, but these causes do not explain the increasing trends. It is suggested that delayed infection could explain NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. METHODS: In a population-based study on 1388 patients with NHL, 354 with Hodgkin's disease (HD) and 1718 healthy controls, the age of first occurrence of bacterial and viral diseases was investigated. Clinical records were perused in one centre to check the anamnestic data. FINDINGS: The age of occurrence of bacterial and viral diseases was significantly higher among NHL patients than in the controls. The association between later age at first bacterial or viral disease was limited to small families (OR= 1.95; 95% confidence intervals 1.26, 3.00, for age 4-8 at first infection; OR=1.91; 1.19, 3.06, for age 9+, compared with less than 4). The association was more obvious for bacterial diseases (possibly for the lower degree of misclassification). High grade lymphomas showed the strongest association. The later age of occurrence of bacterial or viral diseases in NHL patients is consistent with a higher incidence of lymphomas observed in higher social groups. No clear association was found between HD and age at first bacterial or viral diseases. INTERPRETATION: It is proposed that delayed infection could explain the increasing NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. The model of delayed infection has been proposed also to explain increasing prevalence rates of asthma.

Haematopoietic cancer and medical history: a multicentre case control study.

BACKGROUND: Viruses (such as Epstein-Barr virus) and pathological conditions (mainly involving immunosuppression) have been shown to increase the risk of haematolymphopoietic malignancies. Other associations (diabetes, tonsillectomy, autoimmune diseases) have been inconsistently reported. METHODS: The association between different haematolymphopoietic malignancies (lymphomas, myelomas and leukaemias) and the previous medical history has been studied in a population-based case-control investigation conducted in Italy, based on face to face interviews to 2669 cases and 1718 population controls (refusal rates 10% and 19%, respectively). Controls were a random sample of the general population. RESULTS: Previous findings were confirmed concerning the association between non-Hodgkin's lymphoma (NHL) and lupus erythematosus (odds ratio, OR=8.4; 95% CI 1. 6, 45), tuberculosis (OR=1.6; 1.05, 2.5) and hepatitis (1.8; 1.4, 2. 3). An association was found also between NHL and maternal (OR=2.8; 1.1, 6.9) or paternal tuberculosis (OR=1.7; 0.7, 3.9). Odds ratios of 4.0 (1.4, 11.8) and 4.4 (1.1, 6.6) were detected for the association between NHL and Hodgkin's disease, respectively, and previous infectious mononucleosis, but recall bias cannot be ruled out. No association was found with diabetes, tonsillectomy and adenoidectomy. An association with malaria at young age and "low grade" lymphatic malignancies is suggested. One interesting finding was the observation of four cases of poliomyelitis among NHL patients, one among Hodgkin's disease and one among myeloid leukaemia patients, compared with none among the controls (Fisher's exact test for NHL and Hodgkin's disease, p= 0.03, one tail). CONCLUSIONS: Some of these findings are confirmatory of previous evidence. Other observations, such as the putative role of the polio virus and of malaria are new. A unifying theory on the mechanisms by which previous medical history may increase the risk of haematolymphopoietic malignancies is still lacking.

Serum liver enzymes in Turner syndrome.

UNLABELLED: Increased serum concentrations of liver enzymes are sometimes observed, in the absence of clinical symptoms of liver disease, in patients with Turner syndrome. The purpose of this study was to evaluate, in our Turner patients, serum liver enzyme levels and to find a cause for their increase. In 70 Turner patients, serum AST, ALT, GGT levels were evaluated every 6 months during a period of 0. 8-21.9 years. In patients in whom increased values of liver enzymes were found, serological markers for infectious hepatitis, serum hepatitis C virus RNA and virus genotype, IgG and IgA antibodies to gliadin and endomysium, coeruloplasmin, copper, alpha(1)-antitrypsin, total proteins and electrophoresis, IgG, IgA, IgM, fibrinogen, prothrombin, alkaline phosphatase, creatine kinase and total and direct bilirubin were also determined. Antinuclear, anti-smooth muscle and anti-liver-kidney microsome antibodies together with antithyroglobulin and anti-thyroid peroxidase antibodies were determined in all patients and in 166 age-matched female controls. In 22 patients, increased liver enzymes were observed, not related to karyotype. Follow-up showed that the hepatic disorder did not worsen with the time. Serological markers of hepatitis C virus were positive in three patients. When the serum liver enzyme increase was first observed in the other 19 patients with high enzyme levels (group A), 14 patients had never been submitted to hormonal treatment, 4 were on oestrogen/gestagen treatment and 1 was being treated with both growth hormone and oestrogen. Coeliac disease, alpha(1)-antitrypsin deficiency and Wilson disease were ruled out by appropriate investigations. In 8/19 group A patients, antinuclear and/or anti-smooth muscle antibodies were present versus 6/48 of patients with normal liver enzymes (group B). Thyroid antibodies were found in 8/19 patients in group A and in 13/48 in group B. Weight excess SDS was significantly higher in Turner girls with liver enzyme increase. Ultrasonography, performed in 17 patients of group A, showed mild hepatomegaly in 4 and increased echogenicity with fatty infiltration in 6. CONCLUSION: Hepatic abnormalities in Turner syndrome are not progressive. Oestrogen should not be considered the main cause of increased liver enzymes in Turner syndrome since most of our patients with this finding had not been previously treated with oestrogens. An auto-immune pathogenesis might be considered in some cases, whereas the association with weight excess seems the most frequent cause of liver disorder in Turner syndrome.

Attenuated total reflection IR spectroscopy as a tool to investigate the structure, orientation and tertiary structure changes in peptides and membrane proteins.

During the last few years, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) has become one of the most powerful methods to determine the structure of biological materials and in particular of components of biological membranes, like proteins that cannot be studied by x-ray crystallography and NMR. ATR-FTIR requires a little amount of material (1-100 microg) and spectra are recorded in a matter of minutes. The environment of the molecules can be modulated so that their conformation can be studied as a function of temperature, pressure, pH, as well as in the presence of specific ligands. For instance, replacement of amide hydrogen by deuterium is extremely sensitive to environmental changes and the kinetics of exchange can be used to detect tertiary conformational changes in the protein structure. Moreover, in addition to the conformational parameters that can be deduced from the shape of the infrared spectra, the orientation of various parts of the molecule can be estimated with polarized IR. This allows more precise analysis of the general architecture of the membrane molecules within the biological membranes. The present review focuses on ATR-IR as an experimental approach of special interest for the study of the structure, orientation, and tertiary structure changes in peptides and membrane proteins.

Secondary and tertiary structure changes of reconstituted LmrA induced by nucleotide binding or hydrolysis. A fourier transform attenuated total reflection infrared spectroscopy and tryptophan fluorescence quenching analysis.

LmrA, a membrane protein of Lactococcus lactis, extrudes amphiphilic compounds from the inner leaflet of the cytoplasmic membrane, using energy derived from ATP hydrolysis. A combination of total reflection Fourier transform infrared spectroscopy, (2)H/H exchange, and fluorescence quenching experiments was used to investigate the effect of nucleotide binding and/or hydrolysis on the structure of LmrA reconstituted into proteoliposomes. These measurements allowed us to describe secondary structure changes of LmrA during the catalytic cycle. The structure of LmrA is enriched in beta-sheet after ATP binding, and the protein recovers its initial secondary structure after ATP hydrolysis, when P(i) has been released. (2)H/H exchange and fluorescence quenching studies indicate that the protein undergoes two distinct tertiary structure changes during the hydrolysis process. Indeed, the protein alone is poorly accessible to the aqueous medium but adopts a more accessible conformation when ATP hydrolysis takes place. After ATP hydrolysis, but when P(i) is still associated with the protein, the accessibility is intermediate between these two states.