Cerebrospinal fluid (CSF) shunting and ventriculocisternostomy (ETV) in 400 pediatric patients. Shifts in understanding, diagnostics, case-mix, and surgical management during half a century.

OBJECTIVE: To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. METHODS: One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009-2013. This represents our current practice. Our previously reported cohorts of shunted children 1967-1970 (n = 128) and 1985-1988 (n = 138) served as backgrounds for comparison. RESULTS: In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009-2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis was a small but distinctive group in all cohorts with 5, 6 and 3 % respectively. CONCLUSIONS: The case-mix in pediatric patients treated with permanent CSF diversion has changed over the last half-century. With the higher proportion of children with CNS tumor patients and inclusion of the IIH children, the median age at initial surgery has shifted substantially from 3.2 to 14 months. Between the 1960s and the current cohort, 2 years of all-cause mortality fell from 24 to 8 %. Prolonged asymptomatic periods, extending 15 years, were relatively common. Nevertheless, 18 patients experienced shunt failure more than 15 years after last revision, and first-time shunt failure has been observed 29 years after initial treatment. This underscores the importance of life-long follow-up.

Translation, cross-cultural adaptation and validation of the Danish version of the Oxford hip score: Assessed against generic and disease-specific questionnaires.

OBJECTIVES: The Oxford hip score (OHS) is a 12-item questionnaire designed and developed to assess function and pain from the perspective of patients who are undergoing total hip replacement (THR). The OHS has been shown to be consistent, reliable, valid and sensitive to clinical change following THR. It has been translated into different languages, but no adequately translated, adapted and validated Danish language version exists. METHODS: The OHS was translated and cross-culturally adapted into Danish from the original English version, using methods based on best-practice guidelines. The translation was tested for psychometric quality in patients drawn from a cohort from the Danish Hip Arthroplasty Register (DHR). RESULTS: The Danish OHS had a response rate of 87.4%, no floor effect and a 19.9% ceiling effect (as expected in post-operative patients). Only 1.2% of patients had too many items missing to calculate a sum score. Construct validity was adequate and 80% of our predefined hypotheses regarding the correlation between scores on the Danish OHS and the other questionnaires were confirmed. The intraclass correlation (ICC) of the different items ranged from 0.80 to 0.95 and the average limits of agreement (LOA) ranged from -0.05 to 0.06. The Danish OHS had a high internal consistency with a Cronbach's alpha of 0.99 and an average inter-item correlation of 0.88. CONCLUSIONS: This Danish version of the OHS is a valid and reliable patient-reported outcome measurement instrument (PROM) with similar qualities to the original English language version.

Twenty-year outcome in young adults with childhood hydrocephalus: assessment of surgical outcome, work participation, and health-related quality of life.

OBJECT: Shunting of CSF is one of the most commonly performed operations in the pediatric neurosurgeon's repertoire. The 1st decade after initial shunt insertion has been addressed in several previous reports. The goals of the authors' study, therefore, were to determine 20-year outcomes in young adults with childhood hydrocephalus and to assess their health-related quality of life (HRQOL). METHODS: Patients younger than 15 years of age, in whom a first-time shunt insertion was performed for hydrocephalus in the calendar years 1985-1988, were included in a retrospective study on surgical morbidity, mortality rates, academic achievement, and/or work participation. Information concerning perceived health and functional status was assessed using the 36-Item Short Form Health Survey (SF-36) and Barthel Index, which were completed by patients still alive by September 1, 2009. RESULTS: Overall, 138 patients participated, no patient being lost to follow-up. For the 20-year period, the overall mortality rate was 21.7%. The mortality rate was not significantly higher in the 1st decade after initial shunt insertion than in the 2nd decade (p = 0.10). Ten percent of the patients surviving still live with their primary shunt in place, whereas 81% required at least one revision, and among these individual the mean number of revisions was 4.2 (median 3, range 0-26). There was a significantly higher revision rate during the 1st decade after initial shunt insertion compared with the 2nd decade (p = 0.027). The majority of patients live lives comparable with those of their peers. At follow-up, 56% were employed in open-market jobs or were still students, 23% had sheltered employment, and 21% were unemployed. The HRQOL was slightly lower in the hydrocephalic cohort than in the normative population. A significant difference was found in 2 of 8 SF-36 domains-Physical Functioning and General Health. CONCLUSIONS: During the 20-year follow-up period, 81% of the patients required at least one revision of the CSF shunt. The mortality rate was high: 24 patients died in the 1st decade and 6 died in the 2nd decade after implantation of the initial shunt. In total, 4 deaths (2.9%) were due to shunt failure. Shunt placement to treat childhood hydrocephalus has a substantial effect on social functioning in later life, although perceived health was positively found to be better than expected in young adults with hydrocephalus.

Dental anxiety--an epidemiological study on its clinical correlation and effects on oral health.

Pronounced dental anxiety could lead to avoidance strategies to evade dental visits. The aim of the present epidemiological study was to investigate the prevalence and related oral disease patterns of dental anxiety in young adult male soldiers. Therefore, the intensity and frequency of dental anxiety are presented and the correlation with oral clinical findings are evaluated. Three hundred seventy-four soldiers who underwent a compulsory dental check-up were randomly assigned to this study. Psychological parameters were collected based on a protocol integrating the Dental Anxiety Scale (DAS) and the Gatchell Fear Scale (GaFS). Patient-based measures included D3,4MF-scores for dental status and the Community Periodontal Index of Treatment Need (CPITN) for periodontal status. Thirty-two individuals (8.6%) showed DAS-scores of 13 or 14 (anxious), while 4.6% had a DAS-score > or = 15 (highly anxious/phobic). Highest DAS-values were measured among patients' aged 19-29 (n = 262). DMFS-values of anxious and less anxious patients showed only minor differences. However, anxious patients had significantly more carious lesions (P < 0.001). CPITN periodontal values showed no significant differences between both groups. 89.2% of less anxious individuals and 79.6% of anxious patients went for regular dental check-ups. Thus, every tenth patient was considered to have high dental anxiety. Anxiety results in avoidance behaviour, which can only be discovered upon compulsory examinations and which is associated with higher caries morbidity and need for oral rehabilitation. As anxiety has a direct influence on oral health, it should be detected and accounted for in a treatment concept integrating dental and cognitive-behavioural therapeutic approaches.

Intermittent recombinant growth hormone treatment in short children born small for gestational age: four-year results of a randomized trial of two different treatment regimens.

BACKGROUND: Treatment of short children born small for gestational age SGA with recombinant human growth hormone r-hGH increases growth velocity during childhood. As in other indications, the growth velocity in these patients is more marked during the first year of treatment and then decreases. This study was undertaken to evaluate the efficacy of different r-hGH treatment schedules (67 microg/kg/day in a discontinuous or continuous regimen) during the second year of r-hGH treatment by comparing height velocity changes and total gain of height over a 4-year period. METHODS: 58 growth-retarded SGA children aged 2-5 years were randomized to a TOTO regimen (4 years alternating treatment (T) and observation (O), n = 30) or a TTOO regimen (2 years' treatment, followed by 2 years' observation, n = 28). Height velocity HV and total height gain were assessed during the 4-year study. RESULTS: In both groups, HV and HV standard deviation score HV-SDSCA increased during treatment and decreased during observation periods. Interruption of treatment in the TOTO group did not result in a better gain in height standard deviation score H-SDSCA when compared with the TTOO group. After 4 years of study, the gain in H-SDSCA was 1.4 + or - 01 in the TOTO group and 1.6 + or - 0.2 in the TTOO group leading to a mean height of -2.0 + or - 1.0 SDS and -2.0 + or - 0.8 SDS, respectively. The rate of bone maturation was similar in the two groups. CONCLUSIONS: In short SGA children, TOTO and TTOO regimens produced significant improvements in growth during r-hGH treatment. However, treatment interruption after 1 year did not influence the overall gain in height SDS when compared with 2 years' continuous treatment.

Parathyroid adenoma in a subject with familial hypocalciuric hypercalcemia: coincidence or causality?

A middle-aged woman presented with a history of constipation, easy fatigue, depressive mood, lassitude, polydipsia, and polyuria. The patient posed a challenging diagnostic dilemma due to the presence of persistent severe hypercalcemia and relative lack of clinically manifested symptoms. Clinical, biochemical, and genetic examinations confirmed the diagnosis of familial hypocalciuric hypercalcemia as a result of C562Y calcium-sensing receptor mutation, and a coexisting parathyroid adenoma. After adenectomy, the patient's clinical situation improved markedly, and a modest equilibrium hypercalcemia persisted. This case presents an unusual combination of two relatively common endocrine disorders.

Efficient synthesis of enantiopure conduritols by ring-closing metathesis.

Two short synthetic approaches to enantiopure conduritols are described starting from the chiral pool. In both cases, the cyclohexene ring is assembled via ring-closing olefin metathesis. The terminal diene precursers for the metathesis reaction are prepared either from octitols or from tartaric acids. The former route involves a new method for selective bromination of the primary positions in long-chain carbohydrate polyols. Subsequent reductive elimination with zinc then generates the diene. The latter route uses a highly diastereoselective addition of divinylzinc to tartaric dialdehydes for preparation of the dienes.

[Risk factors for low back pain among 1.389 pupils in the 8th and 9th grade. An epidemiologic study]. / Risikofaktorer for laendesmerter hos 1.389 skoleelever i 8.- og 9.-klasse. Et epidemiologisk studie.

INTRODUCTION: The aim of this study was to investigate the frequency and severity of low back pain (LBP) in 13-16-year-old pupils in relation to selected factors, such as anthropometry, physical activity, smoking, hypermobility, and tightness of hamstring muscles. METHODS: The study was designed as a cross-sectional questionnaire-based survey and all the pupils were examined by the school doctor for height, weight, mobility of joints, and general health status. RESULTS: The lifetime prevalence of non-specific LBP was 58.9% and the one-year prevalence was 50.8% with no differences between the sexes. Recurrent/continuous LBP in a moderate to severe degree was recorded in 19.4% of the school children (182 F, 88 M). This was positively correlated to a female gender, a BMI of more than 25 kg/square meter, competitive sports for boys, poor physical fitness, daily smoking, heavy jobs in leisure time, increased use of the health system, and reduced life quality. DISCUSSION: Stepwise logistic regression analysis indicates that a female gender, daily smoking, and heavy jobs are important associated factors for severe LBP in adolescents, with an observed probability of 46% if all factors are present. We do not know yet whether these factors have any causal importance for the development of severe LBP.

Combined cataract and glaucoma surgery.

The management of cataract in glaucoma patients has been continuously changing over the past decade. Extracapsular cataract extraction has been replaced by small-incision phacoemulsification with foldable lenses, and in glaucoma surgery, adjunctive antifibrotic therapy based on risk factors for failure has become standard. Furthermore, new techniques in filtering and nonfiltering surgery have been suggested. The techniques, however, change so fast that well-controlled studies with a follow-up of more than 12 months are increasingly seldom. The purpose of this paper is to review the current literature and to point out some new ideas for the future investigation.

Use of electron microscopic and immunogold labeling techniques to determine polyomavirus recombinant VP1 capsid-like particles entry into mouse 3T6 cell nucleus.

Murine polyomavirus major structural protein VP1 could assemble into capsid-like particles when expressed in the baculovirus system. The recombinant capsid-like particles that were purified by CsCl density gradient centrifugation were capable of packaging host DNA. Electron microscopic and immunogold labeling techniques were used to study the entry of these VP1 recombinant capsid-like particles into mouse 3T6 cells. It was found that these VP1 recombinant capsid-like particles, which lack polyomavirus minor structural proteins (VP2 and VP3), use the same mechanism to enter mouse 3T6 cell cytoplasm and nucleus as that used by native polyomavirus virions.

Impact of antenatal exposure of mice to fenfluramine on cardiac development and long-term growth of the offspring.

The objective of this investigation was to determine, in a placebo-controlled manner, whether antenatal exposure to formulations of fenfluramine and dexfenfluramine impacted cardiac development and long-term growth of exposed mice offspring. One hundred forty-four CD-1 mice were randomized to six treatment groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2 times the equivalent human daily dosage according to body surface area. The drugs were given from 2 weeks before mating until GD 15. The mice ingested each drug at target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and 5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was about 36% in the fetal brain compared with the adult brain. The maternal and the offspring hearts, including mitral and aortic valves, of fenfluramine-exposed mice were indistinguishable from the placebo-exposed mice. The duration of gestation and the litter size were the same between the treatment groups. The mean body weights, body lengths, and head circumferences and early functional testing did not differ significantly between the fenfluramine or dexfenfluramine-exposed offspring and the placebo-exposed offspring. There were no significant treatment differences in growth measured as body weights to PND 120. Neither fenfluramine formulation, given before conception and during gestation, impacted cardiac development and long-term growth of the mice offspring.

RhoA and rho kinase regulate the epithelial Na+/H+ exchanger NHE3. Role of myosin light chain phosphorylation.

The activity of the Na(+)/H(+) exchanger NHE3 isoform, which is found primarily in epithelial cells, is sensitive to the state of actin polymerization. Actin assembly, in turn, is controlled by members of the small GTPase Rho family, namely Rac1, Cdc42, and RhoA. We therefore investigated the possible role of these GTPases in modulating NHE3 activity. Cells stably expressing NHE3 were transiently transfected with inhibitory forms of Rac1, Cdc42, or RhoA and transport activity was assessed using microfluorimetry. NHE3 activity was not adversely affected by either dominant-negative Rac1 or Cdc42. By contrast, the inhibitory form of RhoA greatly depressed NHE3 activity, without noticeably altering its subcellular distribution. NHE3 activity was equally reduced by inhibiting p160 Rho-associated kinase I (ROK), a downstream effector of RhoA, with the selective antagonist Y-27632 and a dominant-negative form of ROK. Furthermore, inhibition of ROK reduced the phosphorylation of myosin light chain. A comparable net dephosphorylation was achieved by the myosin light chain kinase inhibitor ML9, which similarly inhibited NHE3. These data suggest that optimal NHE3 activity requires a functional RhoA-ROK signaling pathway which acts, at least partly, by controlling the phosphorylation of myosin light chain and, ultimately, the organization of the actin cytoskeleton.

Embryonic quail eye development in microgravity.

The US-Russian joint quail embryo project was designed to study the effects of microgravity on development of Japanese quail embryos incubated aboard Mir. For this part of the project, eyes from embryonic days 14 and 16 (E14 and E16) flight embryos were compared with eyes from several groups of ground-based control embryos. Measurements were recorded for eye weights; eye, corneal, and scleral ring diameters; and numbers of bones in scleral ossicle rings. Transparency of E16 corneas was documented, and immunohistochemical staining was performed to observe corneal innervation. In addition, corneal ultrastructure was observed at the electron microscopic level. Except for corneal diameter of E16 flight embryos, compared with that of one of the sets of controls, results reported here indicate that eye development occurred normally in microgravity. Fixation by cracking the shell and placing the egg in paraformaldehyde solution did not adequately preserve corneal nerves or cellular ultrastructure.

Murine polyomavirus infection of 3T6 mouse cells shows evidence of predominant necrosis as well as limited apoptosis.

The current study was developed to determine if polyomavirus infected 3T6 mouse cells evoked an apoptotic or a necrotic mechanism during infection. Infected cells were analyzed by flow cytometry, transmission electron microscopy (TEM), DNA electrophoresis and by measuring caspase-3 enzymatic activity. Infected cells that were analyzed at 72 h post-infection showed the following: flow cytometry analysis revealed a 5% increase in apoptotic cells and a 46% increase in necrotic cells when compared to uninfected cells; electron microscopy showed 10% cells with characteristic apoptotic morphology and 40% with necrotic appearance; caspase-3 activity was found to increase two fold when compared to uninfected cells and DNA fragmentation (laddering) was clearly evident late in infection. It was concluded that infected cells predominantly showed necrosis, although some cells showed apoptosis in late infection. Recombinant capsid-like particles composed of the polyomavirus structural proteins were not able to induce cell death.

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Ag+ alters cell growth, neurite extension, cardiomyocyte beating, and fertilized egg constriction.

BACKGROUND: The Russian Space Agency uses electrochemically generated silver ions (Ag+) to purify drinking water for their space station, Mir, and their portion of the International Space Station. U.S. EPA guidelines allow 10.6 micromol x L(-1) Ag+ in human drinking water for up to 10 d. Studies correlate Ag+ exposure with tissue dysfunction in humans, rats, and mice, and with altered ion transport, skeletal muscle contraction, and embryonic cell constriction in other animal cells. Ag+ effects on cell shape change-related functions have not been assessed. METHODS: Immortalized embryonic human intestinal epithelial cells, freshly explanted embryonic avian nerve cells and cardiomyocytes, and marine fertilized eggs were grown in vitro in medium containing AgNO3. RESULTS: Intestinal cells detach from the substratum and viable cell number decreases by 5-6 d at 5 micromol x L(-1) AgNO3, and faster at higher concentrations. Microtubules appear unaltered in adherent cells. Detached cells are nonviable. Neurite outgrowth and glial cell migration from dorsal root ganglia are inhibited by 3 d at 15 micromol x L(-1) AgNO3 or greater. Contractions stop temporarily in most cardiomyocytes by 5 min at 5 micromol x L(-1) AgNO3 or more, but some cardiomyocytes beat 3 times faster than normal at 7.5-20 micromol x L(-1) AgNO3. Picomolar Ag+ increases marine egg polar lobe constriction within an hour, even in the absence of microtubules. CONCLUSION: Ag+ alters animal cell growth and shape changes by a MT-independent mechanism. This is the first report of Ag+ effects on vertebrate neurite outgrowth, glial cell migration, or cardiomyocyte beat rate.

Possible factors modifying the surgically induced astigmatism in cataract surgery.

PURPOSE: To investigate possible modifiers of the surgically induced astigmatism with special reference to age, gender, preoperative astigmatism, and the intraocular pressure. METHODS & PATIENTS: Data for one hundred and one cataract patients operated on with extracapsular cataract extraction and intraocular lens implantation were prospectively recorded and followed for six years. Different explanatory variables like age, gender, preoperative astigmatism and postoperative intraocular pressure (IOP) were considered. Astigmatic changes were calculated as Naeser's polar values. RESULTS: The surgically induced astigmatism was not significant at one year, but was significantly increased 3- and 6-years postoperatively. At the same time the keratometric axis made a shift toward against-the-rule astigmatism. The postoperative mean-IOP was lower at all controls. Multiple regression analysis showed that a large preoperative astigmatism, a low postoperative IOP, and high age resulted in more surgically induced astigmatism against-the-rule. CONCLUSION: The length and the architecture of the incision are known to have an influence on the surgically induced astigmatism in cataract surgery. In the present study we used a multiple regression analysis model to show a significant correlation between the surgically induced astigmatism and age, preoperative astigmatism, and postoperative IOP.

CeReS-18 inhibits growth and induces apoptosis in human prostatic cancer cells.

BACKGROUND: Polypeptide growth factors are positive and negative regulators of prostatic growth and function, and many positive regulators of growth in the prostate have been extensively studied. However, very few inhibitors of prostate cell proliferation have been identified. We have isolated a unique 18-kDa sialoglycopeptide (CeReS-18) which inhibits cell proliferation of three separate lines of human prostate cancer cells, as well as inducing cellular cytotoxicity via an apoptotic pathway unrelated to the Bcl-2 family of proteins. METHODS: Cell cycle inhibition was analyzed by direct cell counts with a Coulter (Miami, FL) cell counter. Apoptotic cells were analyzed by electron microscopy, annexin V-fluorescein isothiocyanate (FITC) staining, fluorescence microscopy, and propidium iodide uptake measured with a fluorescence-activated cell sorter. Expression of the proteins of the Bcl-2 family was detected by Western blot analysis. RESULTS: We found that CeReS-18 inhibits cell proliferation of androgen-responsive, LNCaP.FGC human prostate cancer cells, as well as of androgen-nonresponsive DU-145 and PC3 human prostate cancer cells. Furthermore a, fivefold increase over the inhibitory concentration of CeReS-18 elicited a cytotoxic response by all three cell lines. We thus characterized the cytotoxic mechanism as apoptotic in nature, and we measured the expression of several members of the Bcl-2 family in PC3 cells upon treatment with CeReS-18. CONCLUSIONS: The data indicate that CeReS-18 is a potent inhibitor of cellular progression through the cell cycle by both androgen-responsive and androgen-nonresponsive human prostate cancer cells. In addition, treatment of both types of cells with increased concentrations of CeReS-18 induces cellular cytotoxicity, characterized as apoptosis.

Ultrastructural observation of altered chloroplast morphology in space-grown Brassica rapa cotyledons.

Photosynthesis will be indispensable in a bioregenerative life-support systems for long space missions. It is critical understand the effects of space on this complex process, especially the loss of gravity. Past has noted changes in plant growth and development; differences about cell size, shape, division, and differentiation; and plastid distribution and structure alterations. The amyloplast-containing columelar cells in root tips were carefully examined since they are likely gravity-sensing sites. Changes on photosynthetic physiology and chloroplast structure have been reported. Both increases and decreases of chlorophyll and carotenoid contents were reported. Structural changes of thylakoid membranes in chloroplasts were observed in pea and Arabidopsis grown in space or clinorotation. Recently, a decrease of CO2 assimilation rate and of electron transport rate of both PSI and PSII on thylakoid membranes were reported in space-grown wheat. These imply an overall decrease of photosynthetic activities, and implicate thylakoid-old structural changes. For example, PSI activity, and its reaction center subunits (PsaA, PsaB, and PsaC) and the LHCIs, were decreased under microgravity. Here, we further examined cellular morphology and ultrastructural features of the chloroplast and its thylakoid membranes by electron microscopy and in situ immunolocalization.