Soldier's social adaptation during the military service

Soldier's social adaptation includes his interpersonal relationships with his environment integration into the military community and the ability to fulfill his role in the military environment and to function adequately outside of it. The aim of this study was to establish the dynamics of soldier's social adaptation during the military service. The study involved soldiers of two platoons of the Armed Forces of Serbia and Montenegro, divided into three groups according to the period of the study: after the first month, after the basic training and at the end of the military service. The instruments applied for the study were sociodemografic questionnaire and Social Adaptation Self-evaluation Scale. Statistical analysis of the obtained data was done using Stident's t-test. The results of the study that soldier's contentment with his professional role and with the quality of his interpersonal relations was highest during the basic training, but the quality of leisure activities was lowest at the end of the military service.     

Pharmacokinetics of modified oral calcitonin product in healthy volunteers

STUDY OBJECTIVE: To assess the preliminary pharmacokinetics, pharmacodynamics, safety, and tolerability of single oral doses of a chemically modified salmon calcitonin product, CT-025, in healthy volunteers. DESIGN: Phase I, exploratory, five-way, open-label, nonrandomized, crossover study. SETTING: Clinical research center. SUBJECTS: Twelve healthy volunteers aged 22-44 years. INTERVENTION: A single oral dose of CT-025 was administered on 5 separate days with a 72-hour washout period between doses. Each dose consisted of CT-025 160 or 320 microg in varying relative concentrations of a mixture of excipients (formulations A, B, and C). MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected for determination of plasma CT-025, total serum calcium, and ionized serum calcium concentrations during the 4-hour period after dose administration. The data are the results from four of the five dosing days, when subjects received CT-025 in high and low concentrations of excipients. The data indicate that CT-025 was rapidly absorbed from the gastrointestinal tract. Mean peak plasma concentrations ranging from 51+/-51-110+/-59 pg/ml were observed 36-54 minutes after administration. Mean terminal elimination half-lives ranged from 54-76 minutes. There was a trend for the mean maximum concentration and area under the plasma concentration-time curve (AUC) from time zero to the time of the last quantifiable plasma concentration to increase with dose. Single oral doses of CT-025 160 and 320 microg were pharmacologically active, inducing a statistically significant decrease in total and ionized serum calcium concentrations. The rate of decrease in ionized serum calcium concentration was significantly related to the CT-025 dose. Single ora doses were well tolerated; some subjects experienced mild and transient nausea. CONCLUSION: Single doses of CT-025 were absorbed into the systemic circulation after oral administration and were well tolerated in healthy volunteers at doses up to 320 microg. These data suggest that oral delivery of salmon calcitonin becomes feasible with this product and support further clinical investigation of CT-025 as a treatment for osteoporosis and osteoporotic bone pain.     

Hormone replacement therapy update: who should we be prescribing this to now?

PURPOSE OF REVIEW: To summarize results from the Women's Health Initiative trial and other recent randomized placebo-controlled trials of hormone replacement therapy, which fundamentally changed our understanding of its risks and benefits. RECENT FINDINGS: The Women's Health Initiative study for the first time provided evidence of harmful effects of hormone replacement therapy on the cardiovascular system and also confirmed significantly increased risk of breast cancer which was previously documented in a metaanalysis. Most recent studies indicate a particularly harmful effect of combined estrogen/progestin regimens in terms of increased breast cancer risk. SUMMARY: The effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, gallbladder, diabetes, cognitive function, health-related quality of life, colorectal cancer, osteoporosis and menopausal symptoms are discussed briefly. The emphasis is on providing concise clinical guidelines for hormone replacement therapy use in new circumstances. We also discuss some alternative therapeutic modalities for women who have menopausal symptoms, but contraindications for hormone replacement therapy.     

Cultivation in rotating bioreactors promotes maintenance of cardiac myocyte electrophysiology and molecular properties

We tested the hypothesis that cardiomyocytes maintained their phenotype better if cultured as three-dimensional tissue constructs than if cultured as confluent monolayers. Neonatal rat cardiomyocytes were cultured on biomaterial scaffolds in rotating bioreactors for 1 week, and resulting tissue constructs were compared with confluent monolayers and slices of native ventricular tissue with respect to proteins involved in cell metabolism (creatine kinase isoform MM), contractile function (sarcomeric myosin heavy chain), and intercellular communication (connexin 43), as well as action potential characteristics (e.g., membrane resting potential, maximum depolarization slope, and action potential duration), and macroscopic electrophysiological properties (maximum capture rate). The molecular and electrophysiological properties of cardiomyocytes cultured in tissue constructs, although inferior to those of native neonatal ventricles, were superior to those of the same cells cultured as monolayers. Construct levels of creatine kinase, myosin heavy chain, and connexin 43 were 40-60% as high as ventricle levels, whereas monolayer levels of the same proteins were only 11-20% as high. Construct action potential durations were 1.8-fold higher than those in ventricles, whereas monolayer action potential durations were 2.4-fold higher. Pharmacological studies using 4-aminopyridine showed that prolonged action potential duration and reduced maximum capture rate in tissue constructs as compared with native ventricles could be explained by decreased transient outward potassium current.     

Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a primary lymphoproliferative T-cell disorder, currently classified as a peripheral T-cell non-Hodgkin's lymphoma. AILD is characterized by generalized lymphadenopathy, hepatosplenomegaly, immunological abnormalities, polyclonal hypergammaglobulinemia and anemia. We report a case of AILD in an 80-year-old male who presented with a generalized pruritic maculopapular eruption and fever following doxycycline administration. The maculopapular rash progressed to formation of confluent nodules, plaques and finally erythroderma with lymphadenopathy and hepatosplenomegaly. Blood analysis revealed an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Lymph node biopsy showed almost complete effacement of the nodal architecture with diffuse proliferation of small vessels forming an arborizing network, surrounded by atypical lymphocytes, usually CD3+ CD4+ and occasionally CD3+ CD8+. There were also larger cells (immunoblastic shape) that displayed CD20 positively, some scattered plasma cells, and eosinophils. Histology of a cutaneous lesion showed spongiosis and infiltration of the epidermis by atypical lymphocytes with large hyperchromatic nuclei, perivascular dermal lymphocytic infiltrate (CD3+) mixed with plasma cells and occasional large immunoblasts (CD20+). During hospitalization the patient developed hemolytic anemia (Coombs positive) and lung metastases. The prognosis of AILD is generally poor, with a median survival of less than 20 months. Our patient died two and a half months after the diagnosis was made due to sepsis caused by Staphylococcus aureus isolated in hemoculture.     

Patterns of metastases in familial and non-familial melanoma

Family history is a strong risk factor for the development of primary melanoma and is associated in a subset with inherited mutations in melanoma susceptibility genes. This study sought to determine whether differences in metastatic pattern exist between patients with a positive family history (FH+) and those with a negative family history (FH-). Such differences could have importance for clinical management and in the determination of the function of both known and putative melanoma susceptibility genes. A retrospective, nested case-controlled study was performed. Of the FH+ cohort (n = 38), 26 were from kindreds with two histologically verified affected first-degree relatives and 12 were from kindreds with three or more affected members, at least two of whom were first-degree relatives. Three FH- controls from the Sydney Melanoma Unit database were matched to each case for age, sex, stage at diagnosis, number of primary melanomas and year of diagnosis (n = 114). There were no statistically significant differences between the two groups with regard to overall survival from initial diagnosis (FH+, 57.4 months; FH-, 50.0 months; P = 0.99), median survival from time of first metastasis (FH+, 15.4 months; FH-, 15.9 months; P = 0.94), or median disease-free interval (FH+, 26.4 months; FH-, 29.7 months; P = 0.73). On multivariate conditional logistic regression analysis, there was no statistically significant difference between the two groups in the probability of developing initial metastases or of ever developing metastases at specific sites. Survival, disease-free interval and distribution of metastatic sites are similar in both familial and non-familial melanoma. Genetic susceptibility for melanoma may lower the threshold for entering an otherwise common molecular pathway for tumour development and evolution.     

Activation of tyrosine kinases in cancer

Receptor and nonreceptor tyrosine kinases (TKs) have emerged as clinically useful drug target molecules for treating certain types of cancer. Epidermal growth factor receptor (EGFR)-TK is a transmembrane receptor TK that is overexpressed or aberrantly activated in the most common solid tumors, including non-small cell lung cancer and cancers of the breast, prostate, and colon. Activation of the EGFR-TK enzyme results in autophosphorylation, which drives signal transduction pathways leading to tumor growth and malignant progression. Randomized clinical trials of the EGFR-TK inhibitor gefitinib have demonstrated clinical benefits in patients with advanced non-small cell lung cancer whose disease had previously progressed on platinum- and docetaxel-based chemotherapy regimens. Bcr-Abl is a constitutively activated nonreceptor TK enzyme found in the cytoplasm of Philadelphia chromosome-positive leukemia cells. STI571 (imatinib mesylate) inhibits the Bcr-Abl TK, blocks the growth of these leukemia cells, and induces apoptosis. STI571 also inhibits other TKs, including the receptor TK c-kit, which is expressed in gastrointestinal stromal tumors. As TK inhibitors become available for clinical use, new challenges include predicting which patients are most likely to respond to these targeted TK inhibitors. Additional clinical trials are needed to develop the full potential of receptor and nonreceptor TK inhibitors for cancer treatment.