Changes in bone mineral density in patients with prostate cancer treated with androgen deprivation therapy

Osteoporosis is a complication of permanent androgen deprivation in men with prostate carcinoma, following either bilateral orchiectomy or treatment with GnRH agonists. The present approach to the problem of osteoporosis includes prevention, adequate follow-up and appropriate treatment as an imperative of contemporary urological and endocrinological management of these patients. Bone densitometry was performed in 18 patients who were on GnRH agonists treatment during 1-3 years. The patients under therapy were followed clinically, PSA (prostate-specific antigen) values were determined and bone scintigraphy was performed. The bone mineral density values in 13 patients indicated osteopenia, whereas in one patient the finding was compatible with osteoporosis. Four patients had normal bone mineral density findings. Bone densitometry should be performed before initiation of treatment with GnRH agonists in order to quantify the therapy-related bone loss. Prevention of development of osteoporosis and its complications depends on the assessment of pharmacological treatment in this group of patients, including e.g. bisphosphonates and possible intermittent androgen deprivation.     

Comparison of digital rectal examination and prostate specific antigen in early detection of prostate cancer

This study compares the value of digital rectal examination (DRE) and prostate specific antigen (PSA) determination in the detection of prostate cancer. 1,000 men aged > or = 50 from the Osijek surroundings were examined. The subjects with prostatitis were excluded from the study. The subjects with elevated concentration of total prostate specific antigen and/or digital rectal examination suspect of carcinoma underwent prostate biopsy. The rate of prostate cancer detection showed to be 3.3% for PSA > 4 ng/ml, 2% for abnormal finding of DRE, and 3.7% for combination of the two methods. Out of 35 patients with prostate cancer detected, 19 had suspect DRE finding and 32 had PSA exceeding 4 ng/ml. Thus, PSA pointed to the diagnosis of prostate cancer in 91.4%, and abnormal finding of DRE in 54.2% of cases, the difference being statistically significant. The positive predictive value was 48.7% for abnormal finding of DRE, 47% for PSA > 4 ng/ml, and 80.0% for the combination of both. Although PSA determination detected a considerable proportion of tumors missed on DRE, the former alone was found to be insufficient as a screening method because of its inadequate sensitivity. When combined with digital rectal examination, the probability of prostate cancer detection increased considerably.     

Youth and AIDS--a study of attitudes,knowledge, behavior and risks in the post-war Croatia

According to the latest reports, the Eastern Europe currently exhibits the greatest relative increase in the number of newly registered HIV infections in the world. At the same time, Central Europe remains relatively spared from the epidemic, with reported rates significantly lower than those in both Eastern and Western Europe. Croatia geographically affiliates to Central Europe, but it has two specific potential risk factors in comparison to neighboring countries: recent War events and a summer season when immigration of large number of tourists from Central and Eastern Europe is expected. Therefore, it is critical to examine AIDS attitudes in young people, increase their knowledge, monitor their behavior and warn on risks in order to prevent larger spread of epidemics from Eastern Europe to Croatia. In this study, we report on a large related survey and education program among 17-year-old high school pupils that was conducted in years immediately following the War (1996-1999).     

Insulin-like growth factor family and combined antisense approach in therapy of lung carcinoma

BACKGROUND: Perturbation in a level of any peptide from insulin-like growth factor (IGF) family (ligands, receptors, and binding proteins) seems to be implicated in lung cancer formation; IGF ligands and IGF-I receptor through their mitogenic and anti-apoptotic action, and the mannose 6-phosphate/insulin-like growth factor II receptor (M6-P/IGF-IIR) possibly as a tumor suppressor. MATERIALS AND METHODS: To determine the identity, role, and mutual relationship of IGFs in lung cancer growth and maintenance, we examined IGF's gene (by RT-PCR) and protein (by immunohistochemistry) expression in 69 human lung carcinoma tissues. We also examined IGF-I receptor numbers (Scatchard analysis) and IGF-II production and release (by Western blot) in IGF-II/IGF-IR mRNA positive and negative lung carcinomas. Finally, the potential role of IGF-IR and IGF-II as growth promoting factors in lung cancer was studied using antisense oligodeoxynucleotides that specifically inhibit IGF-IR and IGF-II mRNA. RESULTS: Thirty-two tumors were positive for IGF-I, 39 for IGF-II, 48 for IGF-IR, and 35 for IGFBP-4 mRNA. Seventeen tumors were concomitantly positive for all four IGFs, whereas 34 were positive for IGF-II, IGF-IR, and IGFBP-4 mRNA. An elevated amount of IGF-II peptide was secreted into the growth medium of cell cultures established from five different IGF-II/IGF-IR mRNA positive lung cancer tissues. The cells also expressed elevated numbers of IGF-IR. Nine IGF-II-negative and 19 IGF-II-positive lung cancers of different stages were selected, and M6-P/ IGF-II receptor was determined immunohistochemically. Most of the IGF-II-negative tumors were strongly positive for M6-P/IGF-IIR. IGF-II-positive tumors were mostly negative for M6-P/IGF-II receptors. Antisense oligodeoxynucleotides to IGF-II significantly inhibited, by 25-60%, the in vitro growth of all six lung cancer cell lines. However, the best results (growth inhibition of up to 80%) were achieved with concomitant antisense treatment (to IGF-IR and IGF-II). CONCLUSION: Our data suggest that lung cancer cells produce IGF-IR and IGF-II, which in turn stimulates their proliferation by autocrine mechanism. Cancer cell proliferation can be abrogated or alleviated by blocking the mRNA activity of these genes indicating that an antisense approach may represent an effective and practical cancer gene therapy strategy.     

Proteomic investigation of natural killer cell microsomes using gas-phase fractionation by mass spectrometry

We have explored the utility of gas-phase fractionation by mass spectrometry (MS) in the mass-to-charge (m/z) dimension (GPF(m/z)) for increasing the effective number of protein identifications in cases where sample quantity limits the use of multi-dimensional chromatographic fractionation. A peptide digestate from proteins isolated from the membrane fraction of natural killer (NK) cells was analyzed by microcapillary reversed-phase liquid chromatography coupled online to an ion-trap (IT) mass spectrometer. Performing GPF(m/z) using eight narrow precursor ion scan m/z ranges enabled the identification of 340 NK cell proteins from 12 microg of digestate, representing more than a fivefold increase in the number of proteins identified as compared to the same experiment employing a standard precursor ion survey scan m/z range (i.e., m/z 400-2000). The results show that GPF(m/z) represents an effective technique for increasing protein identifications in global proteomic investigations especially when sample quantity is limited.     

Clinical importance of significant asimptomatic bacteriuria in newborns and infants during early postnatal period

The aim of the study was to detect newborns at risk for developing renal impairment, and to point out the importance of significant asimptomatic bacteriuria in perinatal period and early infancy. Severe urinary tract anomalies are very often accompanied only by asimptomatic bacteriuria in perinatal period. Three urinalysis ware done after delivery. 212 newborns with significant asimptomatic bacteriuria underwent ultrasound examination, and were followed up to three months. Those with normal findings and with passing bacteriuria in the first 2 months were excluded. Group of 52 newborns underwent radioisotope examination. Frequency of urinary tract anomalies in newborns was 34.6%. Increased risk for renal impairment had children with urinary tract anomalies in close family, urinary tract infection or bacteriuria, EPH gestosis and prepartal symptoms of febrile infection in mother, children with IUGR, strangulated umbilical cord, prolonged jaundice and attacks of peripheral cyanosis in perinatal period.     

Global analysis of the membrane subproteome of Pseudomonas aeruginosa using liquid chromatography-tandem mass spectrometry

Pseudomonas aeruginosa is one of the most significant opportunistic bacterial pathogens in humans causing infections and premature death in patients with cystic fibrosis, AIDS, severe burns, organ transplants, or cancer. Liquid chromatography coupled online with tandem mass spectrometry was used for the large-scale proteomic analysis of the P. aeruginosa membrane subproteome. Concomitantly, an affinity labeling technique, using iodoacetyl-PEO biotin to tag cysteinyl-containing proteins, permitted the enrichment and detection of lower abundance membrane proteins. The application of these approaches resulted in the identification of 786 proteins. A total of 333 proteins (42%) had a minimum of one transmembrane domain (ranging from 1 to14) and 195 proteins were classified as hydrophobic based on their positive GRAVY values (ranging from 0.01 to 1.32). Key integral inner and outer membrane proteins involved in adaptation and antibiotic resistance were conclusively identified, including the detection of 53% of all predicted opr-type porins (outer integral membrane proteins) and all the components of the mexA-mexB-oprM transmembrane protein complex. This work represents one of the most comprehensive proteomic analyses of the membrane subproteome of P. aeruginosa and for prokaryotes in general.     

Analysis of murine natural killer cell microsomal proteins using two-dimensional liquid chromatography coupled to tandem electrospray ionization mass spectrometry

This study describes the application of a single tube sample preparation technique coupled with multidimensional fractionation for the analysis of a complex membrane protein sample from murine natural killer (NK) cells. A solution-based method that facilitates the solubilization and tryptic digestion of integral membrane proteins is conjoined with strong cation exchange (SCX) liquid chromatography (LC) fractionation followed by microcapillary reversed-phase (microRP) LC tandem mass spectrometric analysis of each SCXLC fraction in second dimension. Sonication in buffered methanol solution was employed to solubilize, and tryptically digest murine NK cell microsomal proteins, allowing for the large-scale identification of integral membrane proteins, including the mapping of the membrane-spanning peptides. Bioinformatic analysis of the acquired tandem mass spectra versus the murine genome database resulted in 11,967 matching tryptic peptide sequences, corresponding to 5782 unique peptide identifications. These peptides resulted in identification of 2563 proteins of which 876 (34%) are classified as membrane proteins.     

Unexpected sudden death due to recreational swimming and diving in men in Croatia in a 14-year period

The article deals with 17 sudden deaths which occurred during recreational swimming and diving in men in Croatia in a 14-year period: from January 1, 1998 to December 31, 2011. The sample is taken out from the total number of 61 sudden deaths in men during or immediately after sport or recreational exercise. Included are also sudden deaths of 8 foreigners spending holidays at the Croatian Adriatic Coast. In all of them forensic medicine autopsy was done. Thirteen males from Croatia died during recreational swimming. Three of them were aged 15-29 yrs: one had signs of hypertrophic cardiomyopathy, the second suffered from chronic myopericarditis with left ventricular aneurysm, and the third had cardiomegaly and blood alcohol level of 1.7 per thousand. Five were aged 30-64 yrs: four of them have suffered from coronary atherosclerosis and left ventricular hypertrophy of 15-18-18-22 mm, and one with left ventricular hypertrophy drowned suddenly, probably because of malignant ventricular arrhythmia. The fifth suffered stroke and drowned. Five elderly men, aged 65-85 yrs, have suffered from coronary atherosclerosis, myocardial fibrosis or myocardial scars, and three of them had left ventricular hypertrophy of 19 mm. Four males died during recreational diving. One aged 26yrs drowned, at autopsy he had left ventricular hypertrophy of 17 mm. Three males were middle-aged: two had coronary atherosclerosis, two of them had a severe degree of coronary atherosclerosis and one had coronary atherosclerosis of medium degree but with myocardial fibrosis and left ventricular hypertrophy of 18 mm. Seven male foreigners died, five of them during swimming: two aged 30-64 and two aged 65-85. They all have had coronary atherosclerosis: one of them had an acute myocardial infarction of the posterior wall, and one hypertrophic cardiomyopathy as well. One middle-aged and one elderly man died during diving, and both had an acute myocardial infarction of the posterior wall. One elderly foreign woman died during swimming, she had coronary atherosclerosis and a myocardial scar. In Croatia, death rate during both swimming and diving in men aged 15-29 years amounted to 0.63/1,000.000 (p=1.0000); in those aged 30-64 it reached 0.56/1,000.000 (p=0.3698), and in those aged 65-85 it was 1.41/1,000.000 (p=0.1849). The death rate during swimming in men aged 15-29 amounted to 1.47/1,000.000 (p=0.9864), in men aged 30-64 it reached 0.35/1,000.000 (p=0.2245), and in those aged 65-85 it was 1.41/1,000.000 (the difference is significant, p=0.0472). The death rate during diving in men aged 15-29 was 0.16/1,000.000, and in men aged 30-64 the observed rate was 0.21/1,000.000 (p=1.0000).     

Tonsillolithiasis and orofacial pain

Tonsilloliths are rare calcified structures that usually result from chronic inflammation of the tonsils. Concretions show differences in size, shape and colour. They are usually asymptomatic but can be associated with halitosis, foreign body sensation, dysphagia and odynophagia, otalgia, and neck pain. A patient was referred because panoramic radiography performed by a general dentist revealed radiopaque shadows over the ascending rami of the mandible, located bilaterally: a solitary structure on the higher portion of the right side and two small structures on the left side. Paroxysmal attacks of orofacial pain and symptoms such as dysphagia and swallowing pain on the left side distributed within the tonsillar fossa and pharynx and the angle of the lower jaw were present. The computed tomography images revealed bilateral tonsilloliths. Clinically, there was no sign of inflammation, and the patient's past history revealed an approximately 2-year history of dysphagia, swallowing pain and left-sided neck pain. At the request of the patient, no surgical intervention was carried out. Glossopharyngeal neuralgia is a rare entity, and the aim of this report was to indicate the importance of tonsilloliths as a cause of orofacial pain.