Significance of malperfusion syndromes prior to contemporary surgical repair for acute type A dissection: outcomes and need for additional revascularizations.

OBJECTIVE: The aim of this study was to assess the significance of malperfusion syndromes in patients with acute type A aortic dissection following a contemporary surgical management algorithm and the effects on morbidity, hospital mortality, and long-term survival. We believe that obliteration of the primary tear site with restoration of flow in the true aortic lumen results in decreased need for revascularization of malperfused organ systems. METHODS: Our operative approach aims at replacing the entire ascending aorta, resuspension of the aortic valve with repair or replacement of the sinus segment, and routine open replacement of the arch under hypothermic circulatory arrest with retrograde cerebral perfusion with obliteration of false lumen at the distal arch/proximal descending thoracic aorta, thus reestablishing normal flow in the descending thoracic true lumen. From January 1993 to December 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our institution. Data were collected retrospectively and prospectively. Various types of malperfusion syndromes were present in 26.7% of patients. The organ systems with malperfusion were as follows: cardiac, 7.2%; cerebral, 7.2%; ileofemoral, 12.7%; renal, 4.1%; mesenteric, 1.4%; innominate, 5.4%; and spine, 2.2%. RESULTS: Coronary malperfusion required coronary revascularization in 62.5% of cases. Distal revascularization was needed in 42.9% of patients with ileofemoral malperfusion. Patients with malperfusion were more likely to suffer perioperative myocardial infarction (p<0.001), postoperative coma (p=0.012), delirium (p=0.011), sepsis (p=0.006), acute renal failure (p=0.017), dialysis (p=0.018), and acute limb ischemia (p<0.001). The in-hospital mortality was 30.5% in patients presenting with any malperfusion syndrome while only 6.2% in patients without malperfusion syndrome (p<0.001). Both cardiac (p=0.020) and cerebral malperfusions (p<0.001) were risk factors for in-hospital mortality. The actuarial long-term survival in patients with malperfusion syndrome was estimated by Kaplan-Meier methods to be 67.8%+/-6.1% at 1 year, 54.0%+/-7.0% at 5 years, and 43.1%+/-8.0% at 10 years and for patient without malperfusion 82.7%+/-3.0% at 1 year, 66.3%+/-3.9% at 5 years, and 46.1%+/-6.7% at 10 years (log rank 2.55, p=0.110). Cerebral malperfusion was a significant risk factor for decreased long-term survival (p=0.0002). CONCLUSIONS: The occurrence of malperfusion in patients with acute type A dissection is associated with significant increased risk of in-hospital mortality and complications. Additional revascularization is generally needed in patients with coronary malperfusion and ileofemoral malperfusion. Patients presenting with cardiac and cerebral malperfusions have a high hospital mortality and preoperative cerebral malperfusion is associated with dismal long-term survival.     

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.     

The bladder cooling reflex and the use of cooling as stimulus to the lower urinary tract

PURPOSE: We review the physiology of bladder cooling response in experimental animals and humans, and present its clinical usefulness. MATERIALS AND METHODS: We describe experimental studies of the bladder cooling response, and more recent clinical retrospective and prospective studies of the bladder cooling test in adults and children. RESULTS: Studies indicate the existence of a segmental spinal bladder cooling reflex that originates from specific cold receptors in the bladder and urethral walls supplied by unmyelinated C-afferents. The reflex is positive in neurologically normal infants and children until about age 4 years. It becomes negative with further maturation of the nervous system but may be unmasked by pathological processes that disturb the descending neuronal control of normal voiding. A positive test in a patient with an overactive bladder requires further neurourological evaluation. CONCLUSIONS: The bladder cooling response originates from cold receptors within the walls of the lower urinary tract. The cooling response represents a neonatal reflex that may be unmasked by central neuropathology, analogous to the appearance of the Basbinki sign in pyramidal tract lesions. The bladder cooling test is a simple and valuable tool to support the diagnosis of neurourological disorders.     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

Development of a placental cell culture system for studying the control of mouse placental lactogen II secretion

Fetal placental tissue from 11 days pregnant mice was dissociated in collagenase and DNase solution and then separated on a 40 per cent Percoll gradient. Trophoblast cells banded at a density of 1.05 g/ml. When cultured on rat tail collagen, these cells formed colonies of mono- and binucleate cells varying in size from 40 to 70 microns. At the time of plating, about 13 per cent of the trophoblast cells secreted mouse placental lactogen II (mPL-II) as determined by reverse haemolytic plaque assay. The ratio of mPL-II-producing cells increased significantly in culture and reached 63 per cent after 48 h. The secretion of mPL-II increased continuously during six days of culture, whereas the total protein release was highest after the first day, declined the second day and then remained relatively constant for the last four days of culture. The DNA content of the cells did not change significantly during the six-day period. When the trophoblast cells were incubated with insulin (1 ng/ml to 5 micrograms/ml), a modest but significant reduction in mPL-II secretion was observed. No change in the mPL-II secretion was seen when epidermal growth factor was administered to the culture in concentrations from 1 ng/ml to 10 micrograms/ml. It is concluded that this in vitro culture system is suitable for studying both mPL-II secretion and the differentiation of mPL-II-producing cells.     

Do lipids,blood pressure,diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study

BACKGROUND: Studies on coronary risk factors in men and women are mainly based on mortality data and few compare results of both sexes with consistent study design and diagnostic criteria. This study assesses the major risk factors for coronary events in men and women from the Reykjavik Study. DESIGN: Within a prospective, population-based cohort study individuals without history of myocardial infarction were identified and the relative risk of baseline variables was assessed in relation to verified myocardial infarction or coronary death during follow-up. METHODS: Of the 9681 women and 8888 men who attended risk assessment from 1967-1991, with follow-up period of up to 28 years, 706 women and 1700 men suffered a non-fatal myocardial infarction or coronary death. RESULTS: Serum cholesterol was a significant risk factor for both sexes, with hazard ratios (HR) decreasing with age. Systolic blood pressure was a stronger risk factor for women as was ECG-confirmed left ventricular hypertrophy (women HR 2.89, 95% confidence interval [CI] 1.67-5.01; men HR 1.11 [CI 0.86-1.43]). Fasting blood glucose > or =6.7 mmol/L identified significantly higher risk for women (HR 2.65) than men (HR 2.08) as did self-reported diabetes. Triglyceride risk was significantly higher for women and decreased significantly with age. Smoking increased risk two- to five-fold, increasing with dose, for women, which was significantly higher than the doubling in risk for men. CONCLUSIONS: This large study of the major risk factors compared between the sexes demonstrates similar relative risk of myocardial infarction associated with cholesterol for both sexes, however, the relative risk is higher in women for many other risk factors such as smoking, diabetes, elevated triglycerides and left ventricular hypertrophy.     

Low mannose binding lectin predicts poor prognosis in patients with early rheumatoid arthritis. A prospective study

OBJECTIVE: To determine whether low mannose binding lectin (MBL) is associated with poor prognosis in rheumatoid arthritis (RA) and whether patients with RA have increased frequency of MBL deficiency. METHODS: Patients with recent onset symmetric polyarthritis (< 1 year, median 3 mo) were recruited if they had not been treated longer than 2 weeks with disease modifying drugs. They were reevaluated after 6 months and their disease activity and progression were correlated with their MBL concentration, rheumatoid factor (RF) isotypes, and C-reactive protein (CRP). Sixty-three female patients with advanced RA were also analyzed. RESULTS: Sixty-five patients with early arthritis fulfilled American College of Rheumatology criteria for RA and 52 were followed for 6 months or longer. Low MBL was associated with raised RF, IgA RF in particular (p = 0.02). and also with a combined elevation of IgM and IgA RF (p = 0.035). Patients with low MBL (lowest 25th percentile) showed less improvement after 6 months of treatment than patients in the highest MBL quartile. This applied to the Thompson joint score (p = 0.03) and grip strength (p = 0.004). Low MBL was also significantly associated with radiological joint erosions at recruitment and at 6 month followup (p = 0.039); and the group with advanced RA also showed a significant association between low MBL concentration and radiological damage (p = 0.036). However. neither patient group had increased frequency of MBL deficiency compared to healthy controls. CONCLUSION: Low MBL predicts poor prognosis in patients with early RA.