Lay Perspectives on Receiving Different Types of Genomic Secondary Findings: a Qualitative Vignette Study.

Genome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics' perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease-cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li-Fraumeni syndrome). Participants (N = 29) wrote down their initial reactions, and discussed (N = 23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual's responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals' reactions to this information.

Effect of centralization on long-term survival after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Centralization of pancreatic surgery has resulted in improved short-term outcomes in a number of healthcare systems. The aim of this study was to see whether hospital volume influenced long-term prognosis, use of adjuvant therapy or histopathological evaluation of patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical resection of PDAC in Finland between 2002 and 2008 were identified from national registers. Demographic, histopathological, operative and oncological data were recorded, and the histopathological slides of patients who survived for more than 4 years were reviewed. Operative volume was defined according to the annual rate of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who had undergone resectional surgery for PDAC at 22 centres were included. Patient demographics and resection types did not differ between centres. Thirty- and 90-day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus 5·5 per cent (P = 0·001) and 2·5 versus 11·0 per cent (P = 0·003) respectively. Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage IIB: 65·7 versus 40·6 per cent respectively; P < 0·001), but with no greater use of adjuvant therapy. Significantly more patients survived for 2 years (43·3 versus 29·7 per cent; P = 0·034) and 3 years (25·4 versus 14·1 per cent; P = 0·045) after surgery in HVCs than in LVCs. More information was missing in the histopathological reports from LVCs and MVCs than in those from HVCs (P ≤ 0·002). CONCLUSION: Both short- and long-term survival was significantly better for patients operated on in HVCs. Histopathological analysis appears to be more comprehensive in HVCs.

Effects of seasonal acclimatization on temperature dependence of cardiac excitability in the roach, Rutilus rutilus.

Temperature sensitivity of electrical excitability is a potential limiting factor for performance level and thermal tolerance of excitable tissues in ectothermic animals. To test whether the rate and rhythm of the heart acclimatize to seasonal temperature changes, thermal sensitivity of cardiac excitation in a eurythermal teleost, the roach (Rutilus rutilus), was examined. Excitability of the heart was determined from in vivo electrocardiograms and in vitro microelectrode recordings of action potentials (APs) from winter and summer roach acclimatized to 4 and 18°C, respectively. Under heat ramps (3°C h(-1)), starting from the acclimatization temperatures of the fish, heart rate increased to maximum values of 78±5 beats min(-1) (at 19.8±0.5°C) and 150±7 beats min(-1) (at 28.1±0.5°C) for winter and summer roach, respectively, and then declined in both groups. Below 20°C, heart rate was significantly higher in winter than in summer roach (P<0.05), indicating positive thermal compensation. Cardiac arrhythmias appeared with rising temperature as missing QRS complexes, increase in variability of heart rate, episodes of atrial tachycardia, ventricular bradycardia and complete cessation of the heartbeat (asystole) in both winter and summer roach. Unlike winter roach, atrial APs of summer roach had a distinct early repolarization phase, which appeared as shorter durations of atrial AP at 10% and 20% repolarization levels in comparison to winter roach (P<0.05). In contrast, seasonal acclimatization had only subtle effects on ventricular AP characteristics. Plasticity of cardiac excitation appears to be necessary for seasonal improvements in performance level and thermal resilience of the roach heart.

Gill tissue lipids of salmon (Salmo salar L.) presmolts and smolts from anadromous and landlocked populations.

Composition of membrane lipids from the gills of juvenile Atlantic salmon (Salmo salar) in presmolt and smolt phases of development was compared among anadromous and non-anadromous populations. Three stocks migrating from spawning rivers to either lake (landlocked stock), brackish water or full strength sea water were grown under common garden conditions, and gill lipids and their acyl and alkenyl chains were examined in February (presmolts) and at the end of May (smolts) by mass spectrometry and gas-liquid chromatography. The most remarkable changes upon transition from the presmolt phase to the smolt phase were: (i) increase in the cholesterol/phospholipid ratio, (ii) decrease in the abundance of phosphatidylinositol (PI) content, (iii) increase in the amount of sulfatides, (iv) increase in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species with two highly unsaturated acyl chains, and finally (v) convergence of interstock differences in PC and PE species composition towards a similar lipid composition. Increases in the gill membrane content of cholesterol and sulfatides are discussed as pre-adaptation of salmon gills for salt-secretion, which may occur by increases in membrane microdomains (rafts) harboring ion channels and pumps. The decreases of PI were likely related to adjusting the gill membrane permeability to ions by diminishing prostanoid production. The similarity of those changes among three salmon stocks and the convergence of initially (presmolt phase) different PC and PE species profiles between the stocks towards similar lipid composition suggests that smoltification process of the gill epithelium is largely similar in anadromous and landlocked populations.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Large performance variation does not affect outcome in the Finnish cervical cancer screening programme.

OBJECTIVE: Cytology screening for prevention of cervical cancer can reduce incidence and mortality by more than 80% in settings with good organization and rigorous quality control. Audit studies are essential for reaching and maintaining a high quality of screening. The aim of this study was to evaluate variation in performance indicators by screening laboratory and assess the impact on the effectiveness of screening as indicated by cervical intraepithelial neoplasia grade 3 and above (CIN3+) rates after a negative screen. METHODS: Seven cytology screening laboratories operating during 1990-1999 with a total of 953 610 screening tests performed were included in the study. By linking screening and cancer register files, all cases of CIN3+ diagnosed in the screened population were identified. For 395 CIN3+ cases with a preceding negative screen and 787 controls, a re-evaluation of smears was undertaken to uncover false negative screening tests. Performance parameters and rates of CIN3+ after a negative screen were analysed for interlaboratory heterogeneity. RESULTS: The rates of follow-up recommendations and referrals varied by up to 3.6- (2.8-10.2%) and 4.0-fold (0.03-0.12%), respectively. CIN1, CIN2 and CIN3+ screen detection rates differed by up to 8.5- (0.02-0.17%), 5.4- (0.05-0.25%) and 3.3-fold (0.05-0.18%). False negative rates determined by re-evaluation showed up to 2.1-fold differences (29-62%). Rates of CIN3+ after a negative screen (0.023-0.048%) and as a proportion of total CIN3+ (15-31%) in the screened population were low and did not vary significantly. CONCLUSIONS: There were large variations in the sensitivity-specificity trade-off between laboratories, reflected in all performance indicators as well as in the test validity estimates of the re-evaluation phase, but not in screening effectiveness. Even though performance variations do not always have an impact on the effectiveness of screening, they lead to variations in cost, treatment and psychological burden, and should be addressed.

"I would like to discuss it further with an expert": a focus group study of Finnish adults' perspectives on genetic secondary findings.

Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people's support needs after receiving SFs have received less attention. We explored Finnish adults' perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome. Transcribed focus group discussions were analyzed using inductive thematic analysis. Major themes were immediate shock, dealing with worry and heightened risk, fear of being left alone to deal with SFs, disclosing to family, and identified support needs. Despite their willingness to receive SFs, participants were concerned about being left alone to deal with them. Empathetic expert support and timely access to preventive care were seen as essential to coping with shock and worry, and disclosing SFs to family. Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families.

Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole-genome mutation analysis of the DLBCL components from two composite lymphomas consisting of clonally related NLPHL and DLBCL as a means to identify candidate tumor suppressor genes and oncogenes in NLPHL. The analysis of LP cells for selected mutations of the DLBCL revealed that most mutations are also present in the LP cells, indicating a close relationship between the two components. The analysis of 62 selected genes in NLPHL by targeted ultra-deep sequencing revealed three novel highly recurrently mutated genes (each mutated in ~50% of cases), that is, DUSP2, SGK1 and JUNB. SGK1 was expressed in the LP cells of primary NLPHL cases and in the NLPHL cell line DEV. Administration of an SGK1 inhibitor induced apoptosis in the NLPHL cell line DEV and the DLBCL cell line Farage, suggesting a pathogenetic role of SGK1 in the LP and DLBCL cells. In summary, the present study identifies SGK1, DUSP2 and JUNB as novel key players in the pathogenesis of NLPHL.

Surgery in the air--evacuating Finnish tsunami victims from Thailand.

In connection with the Asian tsunami disaster on December 26, 2004, a specially equipped Finnair B-757 airplane capable of evacuating badly injured patients was remodeled into an ambulance airplane. The vehicle could take up to 22 severely injured or ill patients and intensive care and limited surgical procedures could be provided to the patients. The plane was manned with a civilian medical team of 37 physicians and nurses. The plane left for Thailand to evacuate the most severely injured Finnish citizens within 10 hours of the evacuation decision. A total of 14 patients including 4 critically ill (two on ventilator) were transferred to Helsinki within 32 hours of takeoff. The medical team included a general, an orthopedic and a plastic surgeon. Soft tissue wounds, some of them severely infected, were the most common injuries, followed by extremity fractures and head injuries. The surgical procedures that were performed mid-air included wound surgery, to remove necrotic tissue, and external fixation and fasciotomy for a lower extremity fracture. The facilities under these circumstances would allow performing life-saving procedures to maintain airway and breathing, and surgical procedures of the soft tissues, extremity and pelvic fractures. Cavitary surgery would require additional equipment and resources.

Contribution of sarcolemmal calcium current to total cellular calcium in postnatally developing rat heart.

OBJECTIVE: The aim was to determine the contribution of sarcolemmal Ca influx through L-type Ca current to total cellular Ca in newborn and postnatally developing rat heart. METHODS: Whole cell voltage clamp was used to study L-type Ca current in freshly isolated ventricular cells of 1, 6, 10, 15, 30-day-old and adult (120-150 days) rats. Amplitude, current density, inactivation rate and time integral of Ca current were determined at the experimental temperature of 36 degrees C. Width, length, surface area, volume and surface-to-volume ratio of the isolated cells were also determined. Using the time integral of Ca current and volume of the myocytes the increment in total cellular Ca was calculated for the six developmental stages. RESULTS: The amplitude of Ca current increased strongly during the postnatal maturation from 277 +/- 25 pA at day 1 to 1961 +/- 98 pA in the adult rat (P < 0.001). This increase was due to an almost proportional increase in cell size; accordingly the density of Ca current remained fairly constant, being 16.9 +/- 1.8, 17.0 +/- 1.8, 22.8 +/- 1.4, 21.2 +/- 1.5, 16.2 +/- 2.0 and 15.9 +/- 0.7 pA/pF for 1, 6, 10, 15, 30-day-old and adult rats, respectively. Charge transfer by Cd-sensitive Ca current during 200 ms voltage pulse from -45 mV to 0 mV increased from 7.18 +/- 1.00 pC at day one to 24.80 +/- 1.80 pC in the adult rat heart (P < 0.001). When normalized to the capacitive surface area of the myocytes the charge transfer by L-type Ca current was more than double in newborns (0.429 +/- 0.074 pC/pF) as compared to the adults (0.188 +/- 0.016 pC/pF) (P < 0.01). The difference is explained by slower inactivation rate of Ca current in newborn than adult rats. Time constant of the fast component was 5.92 +/- 0.62 ms and 4.5 +/- 0.4 ms (P < 0.05) for 1-day-old and adult rat, respectively. Time constant of the slow component decreased from 27.7 +/- 2.0 to 21.7 +/- 3.0, although the difference was not statistically significant (P = 0.26). The increment in total cellular Ca due to Ca influx through Ca channels was 54 +/- 9 mumol l-1 in 1-day-old rat and decreased steadily during postnatal maturation to 8 +/- 1 mumol l-1 in the adult rat (P < 0.001). The change is partly due to faster inactivation of Ca current in adults but mainly as a consequence of decreasing surface-to-volume ratio of growing myocytes. Sarcolemmal surface area increases almost 9 times from 1.001 x 10(3) microns2 at day 1 to 8.675 x 10(3) microns2 for the adult rat, whereas increase in cell volume is about 28-fold from 0.991 x 10(3) to 27.74 x 10(3) microns3: accordingly surface-to-volume ratio decreases from 1.05 +/- 0.02 at day 1 to 0.36 +/- 0.01 in the adult rat (P < 0.01). CONCLUSIONS: Contribution of sarcolemmal Ca influx through L-type Ca channels is over 6 times higher in newborn than mature rats. Therefore, the strong dependence of neonatal rat heart on extracellular Ca for contractile activation is, at least partially, explained by greater contribution of L-type Ca current to intracellular Ca.

Restitution of contractility in single ventricular myocytes of guinea pig heart.

OBJECTIVE: Our aim was to assess the extent to which changes in intracellular Ca2+ stores contribute to mechanical restitution in heart muscle. METHODS: Single, isolated guinea pig ventricular cells were voltage clamped at -45 mV and stimulated continuously at 0.5 or 2 Hz with 200 ms depolarizing pulses (35 degrees C). The recoveries of the peak of contraction force (Fp) and the calcium current (ICa) between beats were measured in contractions interpolated at various intervals (td) after a conditioning twitch. Recovery of SR Ca2+ load was inferred from the peak magnitude (Cp) of similarly interpolated contractures, induced by rapid application of 5 mM caffeine. RESULTS: For a conditioning stimulus rate of 0.5 Hz, both Fp and ICa were very small for small td and recovered along similar time courses with a t1/2 of about 50 ms. Cp was maximal at as early a time after a previous contraction as could be measured, at which time Fp was 56% of maximal. Cp declined throughout the stimulus interval to about 50% of its maximal value. Similar results were obtained for a conditioning stimulus rate of 2 Hz, at which rate both Fp and Cp were increased by a factor of 2. CONCLUSIONS: The time course of mechanical restitution is coincident with the recovery of ICa from inactivation. Caffeine-releasable intracellular calcium stores are fully recovered soon after a contraction and well before mechanical restitution is complete.

The rise in incidence of lymphomas in Europe 1985-1992.

A collaborative study was carried out of the descriptive epidemiology of the lymphomas from seven countries across Europe in the period 1985-1992. Careful attention was paid to sources of information and the data quality in close collaboration with expert histopathologists. The data were classified as non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). An attempt was made to put the data into a modified version of the Revised European American Lymphoma (REAL) classification. We observed an overall rise in total NHL throughout the time period in all European countries but no such trend in HD. The increase in NHL overall being 4.2% per annum, representing an increase of 4.8% in males and 3.4% in females per annum, was only marked in middle and old age. Such increases were observed in all participating areas except in Burgundy. Different countries, however, have different base rates, the rates being highest in Scandinavia and the Netherlands. The analysis by subcategory classification suggested that the increase in NHL was confined to the follicle centre cell type, extranodal B-cell, nodal T-cell and nodal lymphomas not otherwise specified, categories. These new observations present a picture of real increase in case incidence with no obvious explanation. The increases in NHL do not appear to be due solely to better diagnoses. Pending other explanations or refutation, these present a compelling picture of an inexorable rise in incidence of this disease.

Fiber capillarization relative to mitochondrial volume in diaphragm of shrew.

The objective was to examine fiber capillarization in relation to fiber mitochondrial volume in the highly aerobic diaphragm of the shrew, the smallest mammal. The diaphragms of four common shrews [Sorex araneus; body mass, 8.2 +/- 1.3 (SE) g] and four lesser shrews (Sorex minutus, 2.6 +/- 0.1 g) were perfusion fixed in situ, processed for electron microscopy, and analyzed by morphometry. Capillary length per fiber volume was extremely high, at values of 8,008 +/- 1,054 and 12,332 +/- 625 mm(-2) in S. araneus and S. minutus, respectively (P = 0.012), with no difference in capillary geometry between the two species. Fiber mitochondrial volume density was 28.5 +/- 2.3% (S. araneus) and 36.5 +/- 1.4% (S. minutus; P = 0.025), yielding capillary length per milliliter mitochondria values (S. araneus, 27.8 +/- 1.5 km; S. minutus, 33.9 +/- 2.2 km; P = 0.06) as high as in the flight muscle of the hummingbird and small bats. The size of the capillary-fiber interface (i.e., capillary surface per fiber surface ratio) per fiber mitochondrial volume in shrew diaphragm was also as high as in bird and bat flight muscles, and it was about two times greater than in rat hindlimb muscle. Thus, whereas fiber capillary and mitochondrial volume densities decreased with increased body mass in S. araneus compared with S. minutus Soricinae shrews, fiber capillarization per milliliter mitochondria in both species was much higher than previously reported for shrew diaphragm, and it matched that of the intensely aerobic flight muscles of birds and mammals.

Na+/Ca2+ exchange current in ventricular myocytes of fish heart: contribution to sarcolemmal Ca2+ influx

Influx of extracellular Ca2+ plays a major role in the activation of contraction in fish cardiac cells. The relative contributions of Na+/Ca2+ exchange and L-type Ca2+ channels to Ca2+ influx are, however, unknown. Using a physiological action potential as the command pulse in voltage-clamped heart cells, we examined sarcolemmal Ca2+ influx through Na+/Ca2+ exchange and L-type Ca2+ channels in crucian carp (Carassius carassius L.) ventricular myocytes. When other cation conductances were blocked, a Ni2+-sensitive current with the characteristic voltage- and time-dependent properties of the Na+/Ca2+ exchange current could be distinguished. At the maximum overshoot voltage of the ventricular action potential (+40 mV; [Na+]i=10 mmol l-1), the density of the Na+/Ca2+ exchange current was 2.99+/-0.27 pA pF-1 for warm-acclimated fish (23 degrees C) and 2.38+/-0.42 pA pF-1 for cold-acclimated fish (4 degrees C) (means +/- s.e.m., N=5-6; not significantly different, P=0.26). The relative contributions of the Na+/Ca2+ exchanger and L-type Ca2+ channels to Ca2+ influx were estimated using two partly different methods. Integration of the Ni2+-sensitive Na+/Ca2+ exchange current and the verapamil- and Cd2+-sensitive L-type Ca2+ current suggests that, during the action potential, approximately one-third of the activating Ca2+ comes through Na+/Ca2+ exchange and approximately two-thirds through L-type Ca2+ channels. An alternative method of analysis, using the inward tail current as a measure of the total sarcolemmal Ca2+ flux from which the Ni2+-sensitive Na+/Ca2+ exchange current was subtracted to obtain the Ca2+ influx through the channels, suggests that L-type Ca2+ channels and Na+/Ca2+ exchange are almost equally important in the activation of contraction. Furthermore, the time course of cell shortening is not adequately explained by sarcolemmal Ca2+ influx through the channels alone, but is well approximated by the sum of Ca2+ influx through the channels and the exchanger. The present results indicate that reverse Na+/Ca2+ exchange in crucian carp ventricular myocytes has sufficient capacity to trigger contraction and suggest that the exchange current makes a significant contribution to contractile Ca2+ during the physiological action potential. The relative significance of channels and exchanger molecules in sarcolemmal Ca2+ entry into crucian carp ventricular myocytes was unaffected by thermal acclimation when determined at 22 degrees C.

Contractile properties of atrial and ventricular myocardium of the heart of rainbow trout oncorhynchus mykiss: effects of thermal acclimation

Atrial and ventricular myocardium perform different tasks in the pumping work of the vertebrate heart, which are reflected in their contractile properties. Although atrial contraction is assumed to have an important role in the function of fish heart, the contractile properties of atrial and ventricular myocardium have not been directly compared in any fish species. The objective of this study was to clarify any contractile differences in the heart of teleost fish and, in particular, to elucidate the contribution of myofibrillar ATPase and intracellular Ca(2+) stores to the characteristics of atrial and ventricular contraction. Experiments were conducted on thermally acclimated rainbow trout Oncorhynchus mykiss to determine whether the effects of temperature adaptation are the same in atrial and ventricular tissue. It was shown that the rate of isometric contraction is much faster in atrial than in ventricular tissue of the fish heart and that acclimation to cold increases the rate of contraction in both cardiac compartments. The rapid contraction kinetics of the atrial tissue were associated with higher myofibrillar ATPase activity and faster Ca(2+) uptake rate of the sarcoplasmic reticulum (SR) compared with ventricular tissue. Similarly, the faster kinetics of contraction following cold acclimation could be attributed to enhancement of the myofibrillar and/or SR function. The atrio-ventricular and temperature-induced differences were also expressed in the recovery of force from inactivation, i.e. in the mechanical restitution. The refractory period and the rate constant of force restitution were shorter in atrial than in ventricular muscle tissue. Similar differences also existed between the tissues of cold-acclimated (CA, 4 degrees C) and warm-acclimated (WA, 17 degrees C) fish. The fast recovery of force from inactivation in the heart of the CA trout was, at least in part, due to more active SR. Furthermore, it was shown that the force of atrial contraction in the CA trout is sensitive to ryanodine (10 (&mgr;)mol l(-)(1)), a Ca(2+)-release channel blocker of SR, at physiological body temperature (4 degrees C) and at a physiological pacing rate (0.6 Hz). This finding indicates that the Ca(2+) stores of SR contribute to activation of cardiac contraction in the fish heart, and that the SR of fish heart is able to retain its Ca(2+) load at low body temperatures, i.e. the Ca(2+ )release channels of SR are not leaky in the cold. The present data show that in the atrial tissue of CA trout, the SR directly contributes to the cytosolic Ca(2+) and that in the atrium and ventricle of CA trout, the SR significantly accelerates the recovery of contractility from inactivation. The fast recovery from inactivation allows relatively high heart rates and therefore adequate cardiac outputs at low environmental temperatures for the cold-active rainbow trout.

Prevalence of gastric metaplasia in the duodenal bulb is low in Helicobacter pylori positive non-ulcer dyspepsia patients.

BACKGROUND: Gastric metaplasia in duodenum is a common phenomena in duodenal ulcer patients. However, the role of gastric metaplasia in patients with non-ulcer dyspepsia is not clear. It is not known either whether Helicobacter pylori infected non-ulcer patients who are CagA-seropositive have gastric metaplasia in duodenum more often than CagA-negative patients. AIMS: To compare prevalence of gastric metaplasia in duodenum in non-ulcer dyspepsia patients according to Helicobacter pylori status. PATIENTS AND METHODS: A series of 400 unselected dyspeptic patients in primary care were investigated. Patients with no endoscopic evidence of organic disease (n=236) were enrolled in the study. Duodenal bulb and gastric biopsies were collected, as well as blood samples for Helicobacter pylori determination. RESULTS: There were no differences between CagA-seropositive and -seronegative Helicobacter pylori infected patients as far as concerns gastric metaplasia in duodenal bulb (20% vs 25%). Helicobacter pylori negative non-ulcer patients more often had gastric metaplastic changes (46%, p<0.0001) in duodenum. CONCLUSION: Helicobacter pylori infection has no major role in development of gastric metaplasia in duodenal bulb in non-ulcer dyspeptic patients. Furthermore, it does not result in positive CagA-serology, an increased risk for gastric metaplasia compared with CagA-seronegative cases.

Kikuchi's disease: report of three cases and an overview.

We describe, to our knowledge, the first native Finnish patients with Kikuchi's histiocytic necrotizing lymphadenitis. The diagnosis was based in all cases on histopathological findings in open biopsy. The disease was first detected in Japan in 1972, but in Scandinavia, until this decade, there had been no cases reported. Our patients were young, otherwise healthy women who had cervical lymphadenopathy, fever, and fatigue as their main symptoms. In two of them, the disease was mild and subsided spontaneously within 2-6 months. One patient with more fulminant lymphadenopathy was treated with antimicrobial and antiinflammatory drugs. She became symptomless in 3 months. The cause of Kikuchi's disease is unknown. A viral or postviral hyperimmune reaction has been proposed as its etiology. Malignant lymphoma and systemic lupus erythematosus are differential diagnoses. Histopathological findings are pathognomonic and pathologists must be aware of its typical characteristics.

Reduction of bone retropulsed into the spinal canal in thoracolumbar vertebral body compression burst fractures. A prospective randomized comparative study between Harrington rods and two transpedicular devices.

STUDY DESIGN: This was a prospective, randomized study. OBJECTIVE: To compare the ability of three methods of internal fixation (Harrington rods, AO internal fixator, posterior segmental fixator) to obtain reduction of intracanal fragments in thoracolumbar vertebral compression burst fractures. SUMMARY OF BACKGROUND DATA: Sixty-seven acute thoracolumbar compression burst fractures of T12 or L1 were randomized into three groups that were treated using one of the three methods. Reduction was accomplished indirectly by distraction applied using the fixation device. METHODS: The spinal canal encroachment was calculated as a percentage of the estimated pre-injury value from serial transverse computed tomographic scans obtained on admission and immediately after surgery. RESULTS: The median preoperative sagittal encroachment of the spinal canal was 37% (range, 0-90%) of the normal diameter. All three methods of internal fixation produced a spinal canal clearance provided that the patient was operated on within 4 days after trauma. The median postoperative encroachment varied from 13% (range, 0-37%) to 22% (range, 0-37%), the best reduction being attained using Harrington rods and the poorest with the posterior segmental fixator. There was a suggestive statistical significance between these two. CONCLUSION: The differences in postoperative spinal canal encroachment and ability to obtain spinal canal clearance observed between the devices studied were small. There seems to be no reason to base the choice of the operative method in thoracolumbar fractures on any hypothetical differences in reductive power between Harrington rods and the AO internal fixator.

Acute temperature change modulates the response of ICa to adrenergic stimulation in fish cardiomyocytes.

The purpose of this study was to investigate how the endogenous catecholamine adrenaline protects sarcolemmal Ca(2+) flux through the L-type Ca(2+) channel (I(Ca)) during acute exposure to cold in the fish heart. We examined the response of I(Ca) to adrenergic stimulation at three temperatures (7 degrees, 14 degrees, and 21 degrees C) in atrial myocytes isolated from rainbow trout acclimated to 14 degrees C. We found that I(Ca) amplitude varied directly with test temperature and was increased by adrenergic stimulation (AD; 5 nM and 1 microM) at all temperatures. However, I(Ca) was significantly more sensitive to adrenergic stimulation at the coldest test temperature. In fact, at 7 degrees C in the absence of AD, I(Ca) was extremely low. The addition of 1 microM AD increased peak I(Ca) 7.2-fold at 7 degrees C, 2.6-fold at 14 degrees C, and 1.6-fold at 21 degrees C and ameliorated the temperature-dependent difference in Ca(2+) influx across the cell membrane. We suggest that this increased adrenergic sensitivity is a critical compensatory mechanism that allows the rainbow trout heart to maintain contractility during acute exposure to cold temperatures. In particular, the tonic level of adrenergic stimulation provided by circulating plasma catecholamines (i.e., in the nM concentration range) may be crucial for effective excitation-contraction coupling in the cold cardiomyocyte.

Computer analysis and plotting of physiologic signals in cardiac muscle research.

A program (Caphys) for IMB-compatible microcomputers is described which facilitates off-line analysis of muscle physiologic signals. Caphys was written as an analysis tool for data acquired through AxoTape program (Axon Instruments). Parameters for time course and amplitude of isometric contractions and intracellularly recorded action potentials are calculated by the program. The features of Caphys include low-pass filtering and derivation of the measured signals. The programs allows also screen display and printer output of the analyzed physiological tracings. Caphys is a suitable extension for the commercially available acquisition software, making the analysis and plotting of primary physiologic data faster and more efficient.