The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Comparison of methylprednisolone and ketoprofen after multiple third molar extraction: a randomized controlled study

In a prospective, double blind, and randomized study, we compared methylprednisolone and ketoprofen after anesthesia for multiple third molar extraction. In addition to paracetamol, 90 patients were allocated to receive intravenously either ketoprofen 100 mg or methylprednisolone 1 mg/kg. Severity of pain was measured with visual analogue scale (VAS) in recovery room. Sixty-three percent of patients receiving methylprednisolone had a VAS score <30 mm compared with 42% of those receiving ketoprofen (P = 0.04), with no difference in the consumption of morphine. We observed only marginal difference between methylprednisolone and ketoprofen to relieve pain after this surgery.     

The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing

Cross talk between fibroblasts and keratinocytes, which maintains skin homeostasis, is disrupted in chronic wounds. For venous leg ulcers and diabetic foot ulcers, a bilayered living cellular construct (BLCC), containing both fibroblasts and keratinocytes that participate in cross talk, is a safe and effective product in healing chronic wounds. To show the importance of both cell types in BLCC, constructs were generated containing only fibroblasts or only keratinocytes and compared directly to BLCC via histology, mechanical testing, gene/protein analysis, and angiogenesis assays. BLCC contained a fully differentiated epithelium and showed greater tensile strength compared with one‐cell‐type constructs, most likely due to formation of intact basement membrane and well‐established stratum corneum in BLCC. Furthermore, expression of important wound healing genes, cytokines, and growth factors was modulated by the cells in BLCC compared with constructs containing only one cell type. Finally, conditioned medium from BLCC promoted greater endothelial network formation compared with media from one‐cell‐type constructs. Overall, this study characterized a commercially available wound healing product and showed that the presence of both fibroblasts and keratinocytes in BLCC contributed to epithelial stratification, greater tensile strength, modulation of cytokine and growth factor expression, and increased angiogenic properties compared with constructs containing fibroblasts or keratinocytes alone.     

Safety and antiviral activity of emtricitabine (FTC) for the treatment of chronic hepatitis B infection: a two-year study

BACKGROUND/AIMS: The aim of this study was to evaluate long term safety and antiviral activity of different doses of emtricitabine given once daily to patients chronically infected with hepatitis B. METHODS: Eligible patients were randomized in a double-blind, parallel study to evaluate 25, 100 or 200 mg once daily doses of emtricitabine for 48 weeks. Patients were then followed for an additional 48 weeks on open-label 200 mg emtricitabine. Serum HBV DNA, ALT, and hepatitis B serology were measured at regular intervals over the 2 years. Resistance surveillance was performed after 1 and 2 years on viremic samples, i.e. > 4700 copies/mL. RESULTS: Emtricitabine was well tolerated and produced a dose proportional antiviral response. After 2 years, 53% of the patients had serum HBV DNA < or = 4700 copies/mL, 33% seroconverted to anti-HBe and 85% had normal ALT. Eighteen percent of the patients who had received 200 mg emtricitabine for 2 years developed resistance mutations. CONCLUSIONS: Emtricitabine was well tolerated and demonstrated a potent antiviral response for up to 2 years in patients with chronic hepatitis B infection. Based on these data, 200 mg emtricitabine once daily was chosen as the optimal dose for future hepatitis B studies.     

Lignocaine in experimental myocardial infarction: failure to prevent neutrophil accumulation and ventricular fibrillation and to reduce infarct size

Growing evidence supports the concept that neutrophils accumulating in reperfused ischaemic myocardium play a detrimental role in evolving infarction. Lignocaine, an antiarrhythmic drug commonly used clinically, interferes with neutrophil function in vitro and potentially in vivo. To test the hypothesis that lignocaine may influence infarct size by reducing neutrophil accumulation in reperfused ischaemic myocardium, 31 dogs underwent a 2 h occlusion of the left anterior descending coronary artery, followed by 6 h of reperfusion. One group of dogs received saline (controls) the other a perfusion of lignocaine 0.06 mg.kg-1.min-1 starting 30 min before coronary occlusion and lasting for the duration of the experiment. Blood lignocaine concentrations at the onset of reperfusion were 3.3(0.6) micrograms.ml-1. 111Indium labelled autologous neutrophils were injected at the time of occlusion and their accumulation in the myocardium measured by digital scintigraphy of heart slices. The area at risk and infarct size were evaluated by planimetry of the heart slices (7 mm) after perfusion of Evans blue dye and triphenyltetrazolium staining. Ventricular fibrillation occurred in six controls and in five dogs receiving lignocaine. The phenomenon occurred early during the occlusion period in the lignocaine group (five dogs) and at reperfusion in controls (five dogs; p less than 0.05). In the remaining 20 dogs, 10 in each group, a linear correlation was found between myocardial 111In labelled neutrophil and circulating neutrophil counts at the onset of reperfusion (r = 0.076, p less than 0.05) and with infarct size (r = 0.96 and 0.74, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurohormones in patients with ischemic left ventricular dysfunction

Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown that in patients with left ventricular dysfunction, several neurohormonal systems were activated, even in the absence of symptoms of congestive heart failure. This suggested that the cardiovascular system was not in a steady state and pointed out potential culprits for the progression of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an important prognostic value. Another value of neurohormonal studies obviously is the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of these neurohormonal systems, such as with the use of the angiotensin-converting enzyme (ACE) inhibitors, particularly captopril and enalapril, and to a lesser extent, with beta-blockers. It can therefore be expected that, in the future, most patients with severe ischemic dysfunction will be treated with an ACE inhibitor. Nonetheless, neurohormonal control is not complete with these drugs; powerful vasoconstrictor forces, such as endothelin-1, remain activated, and an escape of angiotensin II from the control of ACE inhibition may exist. Thus, morbidity (e.g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In the search for further improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action, coupled with powerful coronary vasodilation, might hypothetically delay the progression of ischemic LV dysfunction. In addition, the improved pharmacokinetic profile of these drugs avoiding wide peak and trough variations in plasma levels may avoid triggering some neurohormonal reflexes.     

Action ofin situ nitroglycerin on upper anal canal pressure of patients with terminal constipation

Nitroglycerin (NTG) in situ reduces the pressure of the upper anal sphincter (UAS). We have tested the effects of NTG on the UAS of patients with terminal constipation. We studied two groups of constipated patients. Group 1 consisted of 11 patients (nine females and two males) with hypertonicity of the UAS (>70 mm Hg); age was 49.5±15.6 years. Group 2 consisted of 10 patients (nine females and one male) without hypertonicity; age was 40.1±14.1 years. Group 3 consisted of eight asymptomatic controls (four females and four males); age was 51.7±6.9 years. After a 10-minute resting pressure recording of the UAS with a water-filled balloon, the probe was pulled through the outside and the UAS was assessed after spreading 5 mg of placebo and then 5 mg of NTG on the balloon. Resting pressure (RP), delay of the pressure decrease (DP), pressure after five minutes either during the NTG (PN5) or placebo (PP5) period, and mean duration of the pressure decrease (MD) were measured. None of the subjects experienced a decrease of PP5 vs.RP. All patients in Group 1 (106.2 vs.38.4 mm Hg), Group 2 (57.9 vs.31.4 mm Hg), and controls (62.2 vs.33.7 mm Hg) experienced a significant decrease of pressure of the UAS (P <0.005). Delay of the pressure decrease was less than two minutes, with wide interindividual variability of duration of the pressure decrease. Mild side effects—anal pain and transient headache—were reported in five patients.In situ NTG significantly reduced UAS Pressure in all groups. NTG has to be evaluated in anal pathology, especially in patients with hypertonic sphincter terminal constipation or acute hypertonicity of the sphincter due to a fissure.     

Coronary arteriography in acute transmural myocardial infarction

Coronary arteriography was performed 16 ± 3 days (range 7 to 21 days) in 106 patients with acute transmural myocardial infarction (61 posterior infarct, 45 anterior infarct). Coronary arteriography was performed without serious complications. Only 44 per cent of patients with anterior infarct had total occlusion of the left anterior descending artery while a significant stenosis of the vessel was observed in the others ?27 per cent had a single vessel disease, 49 per cent had two lesions and 22 per cent had three lesions; one patient had angiographically normal coronary arteries. Among the patients with posterior infarction, 21 per cent had one vessel disease and double or triple lesions accounted for 39 per cent of each.Sixty per cent of patients with anterior infarction and 45 per cent with posterior infarction had no collateral vessels. In the others patients collateral circulation had a protective effect only in anterior infarction. Age has no effect on the distribution and number of lesions nor on the development of a collateral circulation. The location and severity of the lesions were not different in patients who presented with arrythmias and those who did not.