Common Genetic Variants in the Myeloperoxidase and Paraoxonase Genes and the Related Cancer Risk: A Review

Modern approaches in health care are moving toward the model of “personalized medicine.” Today, current research in molecular biology and medicine is focused on developing genomic markers with predictive, therapeutic, and prognostic significance. One of the most widespread and significant genomic markers is the single nucleotide polymorphism (SNP), which represents a variation in DNA sequence when a single nucleotide differs between members of a biological species or paired chromosomes in an individual. Antioxidant defense enzymes break down dangerous reactive compounds, called reactive oxygen species, and prevent DNA strand from carcinogen-specific mutations. It is well known that inherited variations in genes that encode antioxidant defense enzymes may modulate individual susceptibility to cancer. In our previous study we have determined the predictive significance of several SNPs of superoxide dismutase (SOD) and glutathione peroxidase gene families in the context of cancer risk. The present review includes a summary and discussion of the current findings evaluating the role of SNPs of the myeloperoxidase (MPO) and paraoxanase (PON) genes in cancer occurrence and development. We suggest that rs2333227 (MPO_ -463G/A) and rs854560 polymorphisms have a great predictive significance; they could probably be utilized as cancer predictors in the future. Also, we recommend further in-depth research for rs11079344 (MPO), rs8178406 (MPO), rs2243828 (MPO), rs662 (PON1), rs705379 (PON1), and PON1_304A/G polymorphisms. These SNPs may become significant cancer-associated biomarkers.     

Variation in urologists' opinions on treatment choice in benign prostatic hyperplasia

The aim of this study was to examine the extent of agreementin a panel of urologists with respect to therapy choice in patientswith benign prostatic hyperplasia (BPH). From a prospectivestudy on treatment choice for BPH (n=670), a stratified sampleof 16 patients was drawn, 4 each from the following actual treatmentgroups: surgery, 5-a-reductase-inhibitor, a-blocker and watchfulwaiting. Detailed information on the results of the variousdiagnostic procedures of these patients was presented to a panelof 58 urologists. Subsequently, they were asked to give theirindividual opinions on the most suitable therapy for each patient.When the information presented was considered as insufficientto make a choice, each urologist was asked to write down whichadditional data were required. In 23% of all cases, the informationwas considered to be insufficient for making an adequate choice.For these cases, urodynamic study (44%) and cystoscopy (24%)were most frequently mentioned as necessary additional procedures.Agreement between the panel members was low. The k value foragreement amongst multiple raters was 0.29 (SE 0.003), whentaking into account all categories and 0.48 (SE 0.005) whenthe category ‘no choice’ was excluded. Analyseson agreement by the extent of the urologist's experience andwork setting showed no large differences between the subgroups.The overall agreement between actual treatment decisions andpanel opinions was highest for surgery (86%), followed by watchfulwaiting (66%) and medical therapies (53% and 28% respectively).Variation in opinions on therapy choice for BPH among urologistsis significant. Given the differing effectiveness, side-effectsand clinical sequelae of the various treatment options, consensusdevelopment and subsequent quality assurance are obviously desirable.     

Laparoscopic drainage of nocardial adrenal abscess in an HIV positive patient

We report a rare case of a nocardial adrenal abscess in an HIV patient that underwent the first drainage of adrenal abscess by laparoscopy. Adrenal abscesses are exceedingly rare in adults and prove to be a diagnostic challenge. Laparoscopic adrenal exploration is both a diagnostic and therapeutic modality with low perioperative morbidity that should be considered in the management of indeterminate adrenal masses and abscesses.     

Effect of Recombinant Human Growth Hormone Therapy on Bone and Clinical Parameters in Girls with Turner's Syndrome

Ferrández, A., Mayayo, E., Arnal, J.M., Garcia, C., Buduel, C., Lasarte, J.J., Anton, R., hyuelo P., and The Spanish Collaborative Group (Endocrine Unit, Children's Hospital, Miguel Servet, Zaragoza, Spain). Effect of recombinant human growth hormone therapy on bone and clinical parameters in girls with Turner's syndrome. Acta Paediatr Scand [Suppl] 356: 87, 1989.
Forty-eight girls with Turner's syndrome were assigned to one of three treatments; recombinant human growth hormone (rhGH) alone, rhGH plus oxandrolone, and rhGH plus ethinyloestradiol. Treatment with rhGH alone or in combination with oxandrolone induced catch-up growth. Older girls treated with rhGH plus ethinyloestradiol showed less marked improvement. The gain in height was associated with a gain in bone diameter and cortical thickness (reflecting increased bone mass). There was a rapid loss of subcutaneous fat. These effects of growth hormone are similar to those observed in patients with growth hormone deficiency.     

A COMPARISON OF NSP-RETICULONS WITH CONVENTIONAL NEUROENDOCRINE MARKERS IN IMMUNOPHENOTYPING OF LUNG CANCERS

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM. © 1997 John Wiley & Sons, Ltd.     

Microcirculatory Dysfunction Induced by Cigarette Smoking

This review deals with the deleterious effects of cigarette smoking on the microcirculation, both in terms of morphological (i.e., vessel wall injury, capillary loss) and functional aspects. The latter concerns predominantly changes in tissue perfusion and its regulatory mechanisms (i.e., reactive hyperemia, sequestration of blood cells in the microcirculation). The mechanisms of action of cigarette smoking on the microcirculation include compromised endothelial‐dependent vasorelaxation, platelet aggregation, endothelial cell dysfunction, and the activation of circulating leukocytes. Through these mechanisms, cigarette smoking elicits the aggregation and adhesion of leukocytes and/or platelets to the microvascular endothelium in venules and arterioles, as assessed by intravital fluorescence microscopy in the hamster skinfold chamber model. This model has allowed us to learn more about the participation of reactive oxygen species, inflammatory mediators, and adhesion molecules in the orchestration of microcirculatory dysfunction after cigarette smoking. In the final part of this review, the clinical consequences of microcirculatory dysfunction are discussed and an outlook is offered on potential prophylactic interventions (i.e., antioxidant vitamins) aimed at abrogating the deleterious action of cigarette smoking on the microcirculation. Microcirculation (2000) 7, 367–384 .     

Clinical Evaluation of a Thin Bipolar Pacing Lead

The main disadvantages of bipolar pacing leads have traditionally been related to their relative thickness and stiffness compared to unipolar leads. In a new "drawn filled tube" plus "coated wire" technology, each conductor strand is composed of MP35N tubing filled with silver core and coated with a thin ETFE polymer insulation material. This and parallel winding of single anode and cathode conductors into a single bifilar coil resulted in a bipolar lead (ThinLine, Intermedics) with a body diameter and flexibility similar to unipolar leads. The lead is tined. polyurethane. with the cathode and the anode made of iridium-oxide-coated titanium (IROX). The slotted 8-mm² cathode tip is coated with polyethylene glycol. a blood soluble material. We present the clinical evaluation results from four pacemaker clinics, where 47 leads (23 atrial-J model 432–04 and 24 ventricular model 430–10) were implanted in 25 patients and followed for up to 2 years. The lead handling characteristics were found to be very satisfactory. Electrical parameters of the leads were measured at implant and noninvasively on postoperative days 1, 2, 21, 42. and months 3, 6, 12, and 24. Mean chronic pulse width thresholds at 2.5 V were 0.14 ± 0.05 ms in the atrium and 0.10 ± 0.02 ms in the ventricle, pacing impedances 443 ± 104 Ω and 520 ± 241 Ω. while median electrogram amplitudes were ≥ 3.5 mV and ≥ 7 m V, respectively. Pacing impedances and thresholds were found to be slightly but statistically significantly higher in unipolar than in bipolar configuration—the findings are explainable bv the lead construction. One of 47 leads failed 3 weeks after implant; the conductors were short circuited due to an error during the manufacturing process. We conclude that the new lead thus far has demonstrated appropriate mechanical and electrical characteristics.     

The Dynamic Behavior of the Diastolic Slope of Monophasic Action Potential Can be Related to the Occurrence and Maintenance of Delayed Afterdepolarization Dependent Arrhythmias

We have described the value of the diastolic slope of the MAP recording at the end of a pacing train as a qualifying marker for the induction of delayed afterdepolarization (DAD) dependent arrhythmias. In the present study (1) the behavior of the slope at different time points during a pacing train was quantified and related to the arrhythmogenic outcome (group A) and (2) termination of DAD dependent VT was related to changes in the slope steepness (group B). In dogs with chronic complete AV block, a MAP was recorded during (1) ventricular pacing, before and after ouabain administration (group A) and (2) 6 spontaneous and 6 lidocaine induced VT terminations (group B). During control (group A), the slope at the end of pacing train was 5 ± 3 mV/s (mean ± SD), independent of the pacing duration. During ouabain, this increased to 20 ± 15 mV/s (P < 0.05), varying with the duration of pacing. The slope was steeper after pacing for 4 seconds, compared to 20 seconds (26 ± 12 mV/s vs 16 ± 13 mV/s, P < 0.05) which corresponded with more frequent VT induction. In spontaneously terminating VTs (group B), CL increased from 353 ± 54 ms at the start to 434 ± 78 ms (P < 0.05) before VT termination. This corresponded with a decreasing steepness of the slope from 19 ± 10 mV/s to 6 ± 5 mV/s (P < 0.05). In lidocaine induced VT termination, the CL and the steepness of the slope showed an identical behavior. There is a dynamic variation in the steepness of the diastolic slope during pacing, which depends on the duration of pacing and predicts arrhythmogenic outcome. Furthermore, a decrease in steepness of the slope during DAD dependent VT can be used to predict VT termination.