Sample carryover and cleaning procedures for asymmetrical flow field-flow fractionation instrument.

Asymmetrical flow field-flow (AF4) fractionation aims in separation of sample components to yield elution of homogenous fractions identified as well-defined peaks in the chromatograms. Separation that occurs in matrix-free open channel potentiates high recovery that can be close to 100%. However, sample properties and separation conditions may induce carryover of sample components during AF4 analysis and in sample sequences. This compromises the quality of the data collected from the online detectors and the downstream offline analytics of the collected fractions. In this study, we followed sample carryover in AF4 using model viruses and analyzed various cleaning solutions and rinse methods to reduce carryover. We introduce an SDS-NaOH -based rinsing and decontamination protocol for the AF4 instrument enabling high-quality data collection.

Posterior Spinal Fusion Extended to Stable Vertebra Provides Similar Outcome in Juvenile Idiopathic Scoliosis Patients Compared with Adolescents with Fusion to the Touched Vertebra.

BACKGROUND AND AIMS:: To compare outcomes between posterior spinal fusion of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis patients with a minimum of 2-year follow-up. The juvenile idiopathic scoliosis patients were fused to the stable vertebra and adolescent idiopathic scoliosis to the touched vertebra. We hypothesized that extending the spinal fusion to the stable vertebra in juvenile patients would provide similar outcomes compared with fusion to the touched vertebra in adolescents. MATERIALS AND METHODS:: A prospective comparative study of 21 consecutive children with juvenile (Risser 0) and 84 adolescent (Risser ⩾2) idiopathic scoliosis (1:4 ratio) undergoing bilateral segmental pedicle screw instrumentation and direct vertebral derotation with a minimum of 2-year follow-up. RESULTS:: Juvenile patients had a significantly larger main curve (58° vs 53°, p = 0.003), more fused levels (p = 0.012) and posterior column osteotomies (p = 0.014) than adolescent patients. Distal adding-on (>10°) was observed in one (4.7%) juvenile and three (3.6%) adolescent patients (p = 0.80), without the need for revisions. Scoliosis Research Society 24 total score averaged 101 in juvenile and 97 in adolescent group at 2-year follow-up (p = 0.047). CONCLUSION:: Posterior spinal fusion with bilateral segmental pedicle screw instrumentation to the stable vertebra provides similar clinical and radiographic outcomes in juvenile patients as compared with adolescents with fusion to the touched vertebra in idiopathic scoliosis. Health-related quality of life as measured using the Scoliosis Research Society 24 questionnaire at the end of follow-up was better in the juvenile as compared with the adolescent group.

Outcomes of growing rod surgery for severe compared with moderate early-onset scoliosis: a matched comparative study.

Aims: The aim of this study was to compare the outcomes of surgery using growing rods in patients with severe versus moderate early-onset scoliosis (EOS). Patients and Methods: A review of a multicentre EOS database identified 107 children with severe EOS (major curve ≥ 90°) treated with growing rods before the age of ten years with a minimum follow-up of two years and three or more lengthening procedures. From the same database, 107 matched controls with moderate EOS were identified. Results: The mean preoperative major curve was 101° (90 to 139) in the severe group and 67° (33° to 88°) in the moderate group (p < 0.001), which was corrected at final follow-up to 57° (10° to 96°) in the severe group and 40° (3° to 85°) in the moderate group (p < 0.001). T1-S1 height increased by a mean of 54 mm (-8 to 131) in the severe group and 27 mm (-4 to 131) in the moderate group at the initial surgery (p < 0.001), and by 50 mm (-17 to 200) and 54 mm (-11 to 212), respectively, during distraction (p = 0.84). The mean number of complications per patient was 2.6 (0 to 14) in the severe group and 1.9 (0 to 10) in the moderate group (p = 0.040). Five patients (4.7%) in the severe group and three (2.8%) in the moderate group developed a neurological deficit postoperatively (p = 0.47). Conclusion: Severe EOS can be treated effectively using growing rods, but the risk of complications is high. Cite this article: Bone Joint J 2018;100-B:772-9.

Membrane-containing virus particles exhibit the mechanics of a composite material for genome protection.

The protection of the viral genome during extracellular transport is an absolute requirement for virus survival and replication. In addition to the almost universal proteinaceous capsids, certain viruses add a membrane layer that encloses their double-stranded (ds) DNA genome within the protein shell. Using the membrane-containing enterobacterial virus PRD1 as a prototype, and a combination of nanoindentation assays by atomic force microscopy and finite element modelling, we show that PRD1 provides a greater stability against mechanical stress than that achieved by the majority of dsDNA icosahedral viruses that lack a membrane. We propose that the combination of a stiff and brittle proteinaceous shell coupled with a soft and compliant membrane vesicle yields a tough composite nanomaterial well-suited to protect the viral DNA during extracellular transport.

Electrophysiological evidence of enhanced distractibility in ADHD children.

Abnormal involuntary attention leading to enhanced distractibility may account for different behavioral and cognitive problems in children with attention deficit hyperactivity disorder (ADHD). This was investigated in the present experiment by recording event-related brain potentials (ERPs) to distracting novel sounds during performance of a visual discrimination task. The overall performance in the visual task was less accurate in the ADHD children than in the control children, and the ADHD children had a higher number of omitted responses following novel sounds. In both groups, the distracting novel sounds elicited a biphasic P3a ERP component and a subsequent frontal Late Negativity (LN). The early phase of P3a (180-240 ms) had significantly smaller amplitudes over the fronto-central left-hemisphere recording sites in the ADHD children than in the control group presumably due to an overlapping enhanced left-hemisphere dominant negative ERP component elicited in the ADHD group. Moreover, the late phase of P3a (300-350 ms) was significantly larger over the left parietal scalp areas in the ADHD children than in the controls. The LN had a smaller amplitude and shorter latency over the frontal scalp in the ADHD group than in the controls. In conclusion, the ERP and behavioral effects caused by the novel sounds reveal deficient control of involuntary attention in ADHD children that may underlie their abnormal distractibility.

Postoperative signs in 96 dogs undergoing soft tissue surgery.

The signs shown by 96 dogs recovering at home after day-case soft tissue operations were assessed by their owners for three days. On the day of the operation there were behavioural changes in all the animals, but by two days after the operation changes in behaviour were detected in only 85 per cent of them. The most common changes were in the dogs' demeanour and their way of moving; there were decreases in overall activity and playfulness, and increases in contact seeking. The dogs also showed signs of pain: the highest ratings were observed on the day of the operation, when the median value on a visual analogue scale from 0 to 100 mm was 43 mm, with a range from 0 to 95 mm. The type of operation significantly affected the signs observed.

Familial hypercholesterolaemia in Finland: common, rare and mild mutations of the LDL receptor and their clinical consequences. Finnish FH-group.

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) receptor which occur in heterozygous form in approximately one in 500 individuals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol levels, accelerated development of atherosclerotic vascular disease, and, if untreated, shortened lifespan. The Finnish population, which represents a genetic isolate, offers exceptional possibilities for genetic-epidemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum of genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations inhibiting cholesterol absorption for the modern treatment of FH.

Neuropsychological analyses of impulsiveness in childhood hyperactivity.

BACKGROUND: Neuropsychological analyses of impulsiveness are needed to refine assessment of attention-deficit hyperactivity disorder (ADHD). AIMS: To investigate specific impairments in hyperactive children in a neuropsychological task battery of impulsiveness, the Maudsley Attention and Response Suppression (MARS) task battery, and to identify the neural substrates. METHOD: Impulsiveness was assessed using different tasks of inhibitory control and time management (MARS) in 55 children with ADHD, other diagnoses and controls. Functional magnetic resonance images were obtained from adolescents with and without ADHD during three of the tasks. RESULTS: Children with ADHD, but not psychiatric controls, were impaired on tests of response inhibition, but not of motor timing. Reduced right prefrontal activation was observed in hyperactive adolescents during higher level inhibition and delay management, but not during simple sensorimotor coordination. CONCLUSIONS: Attention-deficit hyperactivity disorder is characterised by specific deficits in tasks of motor response inhibition, but not motor timing, and by dysfunction of frontostriatal brain regions.

Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer.

Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15-20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40 mg toremifene or 20 mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40 mg toremifene and 20 mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.

Life expectancy of people with intellectual disability: a 35-year follow-up study.

A 35-year follow-up study based on a nation-wide population study of the life expectancy of people with intellectual disability (ID) was undertaken. The study population consisted of a total of 60,969 person-years. A prospective cohort study with mortality follow-up for 35 years was used and the life expectancy of people with ID was calculated for different levels of intelligence. Proportional hazard models were used to assess the influence of level of intelligence and associated disorders on survival. People with mild ID did not have poorer life expectancy than the general population and subjects with mild ID did not have lower life expectancy in the first 3 decades of life. In cases with profound ID, the proportion of expected life lost was > 20% for almost all age groups. The female preponderance was manifested from the age of 60 years onwards, 25 years later than in the general population. Respectively, survival between sexes differed less. Epilepsy and/or hearing impairment increased the relative risk of death for all levels of ID. The prevalence of people with ID over 40 years was 0.4%. People with ID now live longer than previously expected, and the ageing of people with mild ID appears to be equal to that of the general population, posing new challenges to health care professionals.

Localized prostate cancer and 30 years of follow-up in a population-based setting.

Some patients with a histopathological diagnosis of prostate cancer have a tumour that behaves benignly during long-term follow-up. The proportion of patients with such a tumour is unknown, as is the fraction who die of prostate cancer between 10 and 20 y of follow-up. All men aged 45-84 y obtaining a diagnosis of prostate cancer between 1965 and 1993 and being reported to the Finnish Cancer Registry were observed. Death was recorded as caused by prostate cancer or not. We identified 11,500 men with localized prostate cancer and in this group the disease-specific survival rate reached a plateau at approximately 30% after 23 y of follow-up. In the same cohort, 5% of the patients died of prostate cancer during years 11-20 of follow-up. During the observation period, somewhat less than half of the patients with localized prostate cancer who died, died of the disease. This proportion decreased with duration of follow-up. In conclusion, early aggressive therapy for localized prostate cancer is unnecessary, in terms of survival, for those with a benignly behaving tumour (about 30% in this series) or who die of intercurrent disease (about 50% in this series). Such therapy may, however, prolong life for the patients and may cure the patients that die of prostate cancer after more than 10 y follow-up. Prostate Cancer and Prostatic Diseases (2000) 3, 37-42

Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat.

The effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms was studied in chronically ethanol-fed rats. After a 4-day ethanol intoxication period the rats were given s.c. injections of dexmedetomidine (3, 10, or 30 micrograms/kg) or saline (control group) at 10, 16, 22, and 39 h after the last dose of ethanol. The severity of ethanol withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 58 h, blind to the treatments. The results showed that dexmedetomidine at doses 10 and 30 micrograms/kg significantly diminished the severity of the ethanol withdrawal reaction as measured by the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability). Dexmedetomidine at 10 micrograms/kg was the most effective dose, especially in the latter half of the withdrawal period (23-58 h after last dose of ethanol). The results suggest that dexmedetomidine in the treatment of ethanol withdrawal symptoms should be further studied.

Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat.

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.

A practical prognostic index for inoperable non-small-cell lung cancer.

Radical radiotherapy is widely used to treat inoperable non-small-cell lung cancer (NSCLC) although only a small number of patients benefit in the long run from this intensive treatment. There is a small proportion of long-term survivors who might derive advantage from even more aggressive radiotherapy combined with chemotherapy. In order to support optimal treatment selection we have carried out univariate and multivariate analyses of possible prognostic variables in the retrospective data of 502 NSCLC patients treated at one institute with external radiotherapy, both with curative and palliative intent. To obtain more accurate tools for a rational treatment decision, we identified, by using Cox's proportional-hazards model, the five most powerful determinants of overall survival and combined them to a prognostic index. On the basis of only the number of these risk factors (advanced stage, general or metastatic symptoms, poor performance status, anemia and tumor size of at least 7 cm), the patient falls into one of the six possible prognostic groups and these groups turned out to be identifiable as separate prognostic clusters. Thirty-one per cent of the patients have three or more risk factors and a median survival of 5-7 months compared with 18 months for patients without any non-favorable factor. Furthermore, the prognostic factors were so strong that multivariate analyses did not reveal the treatment selection to have any significant influence on survival. As each of the five variables have the advantage of being routinely available, our index is simple enough to be used in daily clinical practice. The clinical value of the prognostic index should be verified by using independent data.

Population views on access to community nursing services in Finland.

The aim of this study was to evaluate potential access to personal community nursing services and the desirability of these services from the point of view of different population groups. Potential access to personal community nursing services was defined as having one or more particular nurses to contact when needing help and advice in health matters. The desirability of these services was defined as the respondents' estimation of how useful they considered it to be for them to have access to personal community nursing services. A computer-assisted telephone interview for the population living in the catchment areas of 10 health centres in Finland was conducted. A random sample of the total population aged 16-79 years was drawn from the population register. Logistic regression revealed that gender, type of community and employment status had best explanatory power in having potential access to personal nursing services and in considering these services desirable. However, many of those who considered personal nursing services very desirable, indicated that they did not have potential access to such services. Most of these persons were elderly and had a chronic disease or disability. Developing access to personal community nursing services particularly for these population. groups appears to be needed.

Acute pancreatitis in patients over 80 years.

OBJECTIVE: To evaluate the occurrence, aetiology and outcome of acute pancreatitis (AP) in patients over 80 years of age, compared with those between 61 and 79 years old. DESIGN: Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: Subgroups of 22 patients 80 years old or over and 139 patients 61-79 years old out of 1058 episodes of AP between 1982 and 1990. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: The percentage of patients aged 80 or more varied from 0 in 1982 to 3% in 1990; 13 (59%) were women compared with 47 (34%) in the 61-79 year old group (p = 0.03). AP in the older group was more likely to be necrotising 9/22 (41%) compared with 23/139 (17%), p = 0.02) and to have been caused by biliary disease 15/22 (68%) compared with 54/139 (39%), (p = 0.01). The overall mortality was 9/22 (41%) in the 80 years and over group and 24/139 (17%) in patients aged 61-79 years (p = 0.02). All 9 patients in their eighties with necrotising pancreatitis died. Neither the mode of treatment nor the Glasgow prognostic scoring had any relation to mortality in the older group. CONCLUSIONS: AP in patients of 80 or more is a serious disease with a high mortality irrespective of standard treatment.

The effect of topical oestradiol on skin collagen of postmenopausal women.

OBJECTIVE: To examine the effect of topical oestradiol on skin collagen and elastin. SUBJECTS: Twelve postmenopausal women, aged 52 to 76 years. INTERVENTIONS: Topical oestradiol treatment on the skin of lower abdomen and the vehicle only on the contralateral site; once a day for three months. MAIN OUTCOME MEASURES: The content of skin hydroxyproline; the levels of the carboxyterminal propeptide of human type I procollagen (PICP) and of the aminoterminal propeptide of human type III procollagen (PIIINP). The number and the quality of collagen and elastic microfibrils. RESULTS: The amount of hydroxyproline in the skin significantly (P = 0.012) increased from 11.8 to 16.3 micrograms (38%) during oestradiol treatment. After treatment, the PICP level in the blister fluid was significantly (P = 0.024) higher on the treated site than on the control site. Also the level of PIIINP increased, but the change was not statistically significant. Electron microscopy showed morphologic improvement of elastic and collagen fibres, while the number of oxytalan and elaunin fibres was unchanged in light microscopy. CONCLUSIONS: Topical oestradiol treatment increases the amount of skin collagen. The increase in the level of PICP and PIIINP in skin blister fluid indicates that oestradiol treatment stimulates collagen synthesis. Furthermore, our results show that topical ostradiol treatment has a greater influence on the amount than on the quality of skin collagen. On the contrary, in elastic tissue the oestradiol treatment will only result in morphologic improvement.

Limited value of ultrasound measured skin thickness in predicting bone mineral density in peri- and postmenopausal women.

Measurement of skin thickness has been proposed to be capable of predicting low bone mineral density and the risk of osteoporosis in postmenopausal women. In order to investigate the association between the two factors, we measured skin thickness on the leg, lower abdomen and forearm by ultrasound scanning, and bone mineral density at the lumbar spine, femoral neck and distal radius by dual-energy X-ray absorptiometry in 60 peri- and postmenopausal women. Only a loose association was found between skin thickness and bone mineral density at any site, the highest correlation being between lumbar bone mineral density and abdominal skin thickness. The results of our study confirm that there is some association between the two factors, but the measurement of skin thickness, although easy and reliable, is not a clinically sufficient method to predict bone mineral density.

Changing strategies in the surgical management of acute necrotizing pancreatitis.

During 1982-90 we changed the surgical treatment of acute necrotizing pancreatitis twice. The operative strategy consisted of early formal resection (n = 13) during 1982-84, early lavational surgery (n = 15) during 1985-87 and late necrosectomy (n = 17) during 1988-90. The mortality rate decreased from 54% to 40% and to 24%, respectively. The pattern of complications changed from bleeding in resections to pseudocysts and fistulas in late necrosectomy. Sepsis and multiorgan failure were still main problems. These results led us to begin a prospective study of planned repeated debridement by open packing after delayed necrosectomy.

Astrocytes as targets for CNS effects of organic solvents in vitro.

The aim of the study was to evaluate astrocytes in vitro as a model for studies of solvent neurotoxicity. Primary astrocyte cultures were established from newborn rat cerebella. The cells were cultured in the modified Minimum Essential Medium (MEM), and the neural membranes isolated from cultures were exposed to solvents in incubation mixtures containing different solvent concentrations (3, 6, and 9 mM) for one hour. The activity of membrane-bound total ATPase was determined after exposure to aromatic hydrocarbons (benzene, toluene, xylene, styrene and ethylbenzene), and to n-hexane and cyclohexane. The enzyme activities were decreased by aromatic hydrocarbons linearly according to the log dose and in order to the log lipid/water partition coefficients, benzene having the smallest and ethylbenzene the greatest effect in all concentrations studied. Cyclohexane caused much smaller enzyme inhibition (18% of control activity in 9 mM concentration) than ethylbenzene (67% in 9 mM), in spite of very similar partition coefficients. N-hexane had clearly slighter enzyme inhibiting effect than aromatic hydrocarbons, in spite of its markedly greater lipophilicity. In addition to lipophilicity, the structure of solvent molecule seems to be important when considering the CNS toxicity. These results suggest that organic solvents exert their toxic effects on CNS, at least in part, by disturbing ATPase-dependent astrocytic regulatory functions.