Primary pulmonary hypertension

Justification of early treatment of nocturnal enuresis is founded in the negative psychological impact on the child. In fact nocturnal enuresis delays early autonomy and socialisation by decreasing in self-esteem and self-confidence. Nocturnal enuresis classification is the preliminary step to correct therapy. Enuresis must be classified as primary (never acquired nocturnal control) or secondary (at least 6 months of dry nights). A child is also classified as having monosymptomatic enuresis if she/he experienced only night wetting and symptomatic enuresis if she/he experienced night wetting associated with diurnal voiding symptoms (urinated > or = 7 times a day, urgency, damp pants, squatting, holding the perineum, sitting on one heel). Monosymptomatic patients must be treated with desmopressin nasal spray at the daily dose of 20 micrograms at bed time. If the reduction of at least the 50% of the basal number of the wet nights is not achieved, the dosage must be increased until 40 micrograms. For patients affected by rhinitis or asthma, desmopressin is now available in tablets. In symptomatic patients desmopressin therapy must be associated to oxybutinin (5 mg x 2). Therapy interruption must be gradual with desmopressin reduction of 10 micrograms every 30 days. In symptomatic patients oxybutinin must be introduced only at bed time. The efficacy of the drugs depends on the therapy length. The highest percentage of success is obtained if the treatment is protracted for at least six months. Antidepressants are also used for nocturnal enuresis especially imipramine. The dosage varies between 0.5-1.5 mg/ kg/daily. As plasmatic levels are achieved only in 30% of treated patients, a 3-5 fold increase in suggested. Nevertheless these levels result in near toxic threshold concentration. Sporadic treatment purposes include amytriptiline, diclofenac sodicum, viloxsazine and methilphenidate if giggle incontinence is present. Non responders may be treated with alarm. If after 16 weeks of treatment no success is obtained alarm use must be interrupted.     

Enalapril-induced renal artery thrombosis in unilateral renal artery stenosis

Intravascular adhesion of leucocytes plays a role in the pathogenesis of acute and chronic vascular disease. Regular aerobic exercise seems to protect against vascular disease. Since leucocyte adhesion is mediated by integrins, we tested the hypothesis that surface expression of the integrin adhesive receptors LFA-1 (cd11a/cd18), MAC-1 (cd11b/cd18), gp 150/95 (cd11c/cd18), and VLA-4 (cd29/cd49) is decreased by moderate endurance exercise. Surface expression of integrins was measured by FACS analysis in 19 healthy subjects (16 males, 3 females, 36.6 +/- 8.7 years, 177.1 +/- 7.5 cm, 70.3 +/- 8.1 kg) before and after submaximal exercise (3 h run) using monoclonal antibodies against cd11a, cd11b, cd11c, cd18, cd29 and cd49. In addition, we compared resting integrin expression in this group with a group of sedentary subjects (19 males, 6 females, 29.3 +/- 5.3 years). White blood cell count increased from 5300 ml(-1) to 9740 ml(-1) during exercise (P < 0.001). Nevertheless, the expression (indicated by the mean log fluorescence) of cd11a (94 +/- 24 vs. 78 +/- 14) and cd18 (128 +/- 31 vs. 102 +/- 21) on lymphocytes and of cd11a (104 +/- 25 vs. 85 +/- 16), cd11c (497 +/- 171 vs. 408 +/- 126) cd29 (109 +/- 16 vs. 89 +/- 16), cd49 (69 +/- 8 vs. 54 +/- 11) on monocytes was decreased after exercise (all P < 0.05). In contrast, integrin expression on granulocytes was not altered by exercise. Comparison of exercising and sedentary subjects showed a significantly decreased expression of integrins in exercising subjects. Our results demonstrate that moderate exercise leads to decreased expression of integrin receptors on leucocytes. This decreased expression of adhesion molecules may result in decreased adhesion and infiltration of leucocytes into the vessel wall. This phenomenon may play a role in the beneficial effect of moderate exercise in prevention of acute and chronic vascular disease.     

Limb development: marginal fringe benefits

Recent results show that in the developing Drosophila wing, the secreted pioneer protein Fringe regulates the sensitivity of the Notch signaling pathway to different ligands. This provides a likely mechanism by which Fringe-like molecules may control patterning in both Drosophila and vertebrates.     

Prognostic significance of tumour markers in endometrial cancer

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.     

Physiology of spinal anaesthesia and practical suggestions for successful spinal anaesthesia

There are numerous physiological effects of spinal anaesthesia. This chapter focuses on the physiological effects that are of clinical relevance to the anaesthesiologist, and provides suggestions for successful management of this simple and popular technique. The mechanisms and clinical significance of spinal-anaesthesia-induced hypotension, bradycardia and cardiac arrest are reviewed. The increasing popularity of ambulatory spinal anaesthesia requires knowledge that long-acting local anaesthetics, such as bupivacaine, impair the ability to void far longer than short-acting local anaesthetics, such as lidocaine. The importance of thermoregulation during spinal anaesthesia, and the clinical consequences of spinal-anaesthesia-induced hypothermia are reviewed. Effects of spinal anaesthesia on ventilatory mechanics are also highlighted. Lastly, the sedative and minimum-alveolar-concentration-sparing effects of spinal anaesthesia are discussed to reinforce the need for the judicious use of sedation in the perioperative setting.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

The kininogen gene family in obstructive uropathy

Because many patients present themselves for treatment with both craniofacial and craniocervical pain, 2 questions arise: (1) What are the sensory and motor consequences of dysfunction in either of these areas on the other? (2) Do craniofacial and craniocervical pain have a similar cause? These questions formed the impetus for this review article. The phenomenon of concurrent pain in craniofacial and cervical structures is considered, and clinical reports and opinions are presented regarding theories of cervical-to-craniofacial and craniofacial-to-cervical pain referral. Because pain referral between these 2 areas requires anatomic and functional connectivity between trigeminally and cervically innervated structures, basic neurophysiologic and neuroanatomic literature is reviewed. The published data clearly demonstrate neurophysiologic and structural convergence of cervical sensory and muscle afferent inputs onto trigeminal subnucleus caudalis nociceptive and non-nociceptive neurons. Moreover, changes in metabolic activity and blood flow in the brainstem and cervical dorsal horn of the spinal cord in both monkeys and cats have been demonstrated after electric stimulation of the V1-innervated superior sagittal sinus. In conclusion, the animal experimental data support the findings of human empiric and experimental studies, which suggest that strong connectivity exists between trigeminal and cervical motor and sensory responses.