A rare cutaneous tumour.

A clinicopathological correlation case of a rare cutaneous tumour, which demonstrated a very rare recurrence with uncertainty remaining over the long-term prognosis for the patient. Click https://www.wileyhealthlearning.com/#/online-courses/a975ab43-2d48-46fb-8dba-7df9792fd778 for the corresponding questions to this CME article.

Swedish references for weight, weight-for-height and body mass index: The GrowUp 1990 Gothenburg study.

AIM: To update the Swedish references for weight, weight-for-height and body mass index (BMI) considering the secular trend for height but not including that for weight. METHODS: Longitudinal measures of height and weight were obtained (0-18 years) from 1418 (698 girls) healthy children from the GrowUp 1990 Gothenburg cohort born at term to non-smoking mothers and Nordic parents. A total of 145 individuals with extreme BMI value vs GrowUp 1974 BMI SDS reference were excluded (0-2 years: ±4SDS, 2 < years: -3SDS, +2.3SDS). References were constructed using the LMS method. RESULTS: The updated weight reference became similar to the GrowUp 1974 Gothenburg reference: BMI increased rapidly up to lower levels in the 1990 cohort during infancy/early childhood, similar in both groups in late childhood/adolescence, despite lower values at +2SDS. Compared with the WHO weight standard, median and -2SDS weight values were higher for the 1990 cohort, whereas +2SDS values were lower, resulting in narrower normal range. Median values were greater and ±2SDS narrower for the 1990 vs the WHO weight-for-height reference. International Obesity Task force (IOTF) BMI lines for definitions for over- and underweight were added. CONCLUSION: We present updated references for weight, weight-for-height and BMI, providing a healthy goal for weight development when monitoring growth within healthcare settings.

Nordic populations are still getting taller - secular changes in height from the 20th to 21st century.

AIM: The study aims to investigate secular changes in adult height among Nordic reference populations during the last four decades and in parents of Swedish study participants, and to study during which growth phase(s) infancy, childhood or puberty changes in height and tempo occurred. METHODS: Length and height data were obtained from publications on populations used as current and previous national height references in Denmark, Finland, Norway and Sweden. Measurements from birth until adult height and original parental heights of participants in Swedish reference populations born 1956, 1974, and 1990 were used. RESULTS: Adult height has increased progressively in Nordic populations born in 1950s-1990s; for females by 6 mm/decade Norway, 4 mm; Sweden, 6 mm; Finland and Denmark, 7 mm; for males by 9 mm/decade, in Sweden, 5 mm; Finland, 7 mm; Denmark 8 mm; Norway, 15 mm. This was due to more growth during childhood despite earlier timing of mid-puberty. Heights of Swedish parents born 1920s-1960s increased 11 mm/decade for mothers, 14 mm/decade for fathers. CONCLUSION: The Nordic countries comprise some of the tallest populations in the world yet continue to show a positive secular change in adult height alongside a faster tempo of growth by earlier timing of puberty, highlighting the need to regularly update national height references.

Estimating secular changes in longitudinal growth patterns underlying adult height with the QEPS model: the Grow Up Gothenburg cohorts.

BACKGROUND: Over the past 150 years, humans have become taller, and puberty has begun earlier. It is unclear if these changes are continuing in Sweden, and how longitudinal growth patterns are involved. We aimed to evaluate the underlying changes in growth patterns from birth to adulthood by QEPS estimates in two Swedish cohorts born in 1974 and 1990. METHODS: Growth characteristics of the longitudinal 1974 and 1990-birth cohorts (n = 4181) were compared using the QEPS model together with adult heights. RESULTS: There was more rapid fetal/infancy growth in girls/boys born in 1990 compared to 1974, as shown by a faster Etimescale and they were heavier at birth. The laterborn were taller also in childhood as shown by a higher Q-function. Girls born in 1990 had earlier and more pronounced growth during puberty than girls born in 1974. Individuals in the 1990 cohort attained greater adult heights than those in the 1974 cohort; 6 mm taller for females and 10 mm for males. CONCLUSION: A positive change in adult height was attributed to more growth during childhood in both sexes and during puberty for girls. The QEPS model proved to be effective detecting small changes of growth patterns, between two longitudinal growth cohorts born only 16 years apart.

Pubertal height gain is inversely related to peak BMI in childhood.

BACKGROUND: Childhood BMI may influence subsequent growth in height as well as the timing of puberty. The aim of the present study was to investigate associations between BMI in childhood and subsequent height gain/pubertal growth. METHODS: Longitudinal growth data were used (GrowUp1990Gothenburg cohort, n = 1,901). The QEPS growth-model was used to characterize height gain in relation to the highest BMISDS value between 3.5 and 8 y of age. Children were defined as overweight/obese (OwOb) or normal weight/underweight (NwUw), using the 2012 International Obesity Task Force criteria. RESULTS: A negative association between childhood BMISDS and pubertal height gain was observed. Already at birth, OwOb children were heavier than NwUw children, and had a greater height velocity during childhood. Onset of puberty was 3.5/3.0 mo earlier in OwOb girls/boys, and they had 2.3/3.1 cm less pubertal height gain from the QEPS-models specific P-function than NwUw children. Adult height was not related to childhood BMI. CONCLUSION: We found that pubertal height gain was inversely related to peak BMI in childhood. Higher childhood BMISDS was associated with more growth before onset of puberty, earlier puberty, and less pubertal height gain, resulting in similar adult heights for OwOb and NwUw children.

Insight into human pubertal growth by applying the QEPS growth model.

BACKGROUND: Computerized mathematical models describing absolute and relative individual growth during puberty in both cm and standard deviation (SD)-scores are lacking. The present study aimed to fill this gap, by applying the QEPS-model that delineates mathematically the specific pubertal functions of the total growth curve. METHODS: Study population used was the individual growth curves of the longitudinally followed cohort GrowUp1974 Gothenburg (n = 2280). The QEPS-model describes total height as (T)otal-function: a combination of four shape-invariant growth functions, modified by time-scale and height-scale parameters: a (Q)uadratic-function for the continuous growth from fetal life to adulthood; a negative (E)xponential-function adds the rapid, declining fetal/infancy growth; a (P)ubertal-function the specific pubertal growth spurt; a (S)top-function the declining growth until adult height. A constructed variable, MathSelect, was developed for assessing data-quality. CIs and SD-scores for growth estimates were calculated for each individual. QEPS-model estimates used for pubertal growth; from the T-function: onset of puberty as minimal height velocity (AgeT ONSET ); mid-puberty as peak height velocity (AgeT PHV ); end of puberty as height velocity decreased to 1 cm/year (AgeT END ); duration of different intervals and gain (AgeT ONSET-END and Tpubgain); from the P-function: onset of puberty, estimated as growth at 1% or 5% (AgeP1 , AgeP5); mid-puberty as 50% (AgeP50) and PHV (AgeP PHV ); end of pubertal growth at 95 or 99% (AgeP95, AgeP99); duration of different intervals and pubertal gain (Ppubgain; P max ); from the QES-function: gain (QESpubgain) . RESULTS: Application of these mathematical estimates for onset, middle and end of puberty of P-function, QES-function, and T-function during puberty showed: the later the onset of puberty, the greater the adult height; pubertal gain due to the P-function growth was independent of age at onset of puberty; boys had higher total gain during puberty due to P-function growth than to QES-function growth; for girls it was reversed. CONCLUSIONS: QEPS is the first growth model to provide individualized estimates of both the specific pubertal growth function and the total growth during puberty, with accompanying SD-scores and Cis for each individual. These QEPS-derived estimates enable more in-depth analysis of different aspects of pubertal growth than previously possible.

Metformin Improves Survival in Patients with Pancreatic Ductal Adenocarcinoma and Pre-Existing Diabetes: A Propensity Score Analysis.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders. RESULTS: We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81-0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all). CONCLUSIONS: Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.

Hyperglycemia in Acutely Ill Non-diabetic Children in the Emergency Rooms of 2 Tertiary Hospitals in Lagos, Nigeria.

OBJECTIVES: The study aimed to determine the prevalence of hyperglycemia in sick children admitted into the emergency rooms and to investigate its relationship with adverse outcomes. METHODS: A prospective study involving 2 tertiary hospitals in Lagos. Study subjects included all children aged beyond 1 month. An Accu-Chek Active glucometer was used for the bedside blood glucose determination. Hyperglycemia was defined as blood glucose greater than 7.8 mmol/L. RESULTS: A total of 1045 patients were recruited with hyperglycemia being recorded in 135 patients (prevalence rate of 12.9%). Mean age of the hyperglycemic patients was 29.0 ± 31.23 months. Prevalence rates of hyperglycemia among the leading diagnoses were 17.4% in acute respiratory tract infections, 11% in malaria, 15.3% in septicemia, 14.9% in gastroenteritis, and 18.2% in burns. Other conditions include sickle cell anemia, meningitis, and malnutrition. Mortality rate was significantly higher overall in hyperglycemic compared with the normoglycemic patients (15.4% vs 8.0%, P = 0.011). With regard to specific diagnoses, significantly higher mortality rates were recorded in hyperglycemic patients with acute respiratory tract infections (28% vs 8%, P = 0.011) and malaria (21.4% vs 5.0%, P = 0.006) than in their normoglycemic counterparts. CONCLUSIONS: Hyperglycemia is common in ill children admitted to the emergency rooms and is associated with 2 to 4 times higher mortality in common childhood diseases encountered. Blood glucose determination is important in all acutely ill children at presentation. The practice of empirical administration of intravenous glucose in some resource-constrained facilities where blood glucose testing facilities are not readily available should be discouraged.

The regulated synthesis of a Bacillus anthracis spore coat protein that affects spore surface properties.

AIMS: Examine the regulation of a spore coat protein and the effects on spore properties. METHODS AND RESULTS: A c. 23 kDa band in coat/exosporial extracts of Bacillus anthracis Sterne spores varied in amount depending upon the conditions of sporulation. It was identified by MALDI as a likely orthologue of ExsB of Bacillus cereus. Little if any was present in an exosporial preparation with a location to the inner coat/cortex region established by spore fractionation and immunogold labelling of electron micrograph sections. Because of its predominant location in the inner coat, it has been renamed Cotγ. It was relatively deficient in spores produced at 37°C and when acidic fermentation products were produced a difference attributable to transcriptional regulation. The deficiency or absence of Cotγ resulted in a less robust exosporium positioned more closely to the coat. These spores were less hydrophobic and germinated somewhat more rapidly. Hydrophobicity and appearance were rescued in the deletion strain by introduction of the cotγ gene. CONCLUSIONS: The deficiency or lack of a protein largely found in the inner coat altered spore hydrophobicity and surface appearance. SIGNIFICANCE AND IMPACT OF THE STUDY: The regulated synthesis of Cotγ may be a paradigm for other spore coat proteins with unknown functions that modulate spore properties in response to environmental conditions.

Timing of menarche and pubertal growth patterns using the QEPS growth model.

Objectives: To explore the timing of menarche, postmenarcheal growth, and to investigate the impact of various variables on menarcheal age and postmenarcheal and pubertal growth. Study Design: This longitudinal community population-based study analyzed pubertal growth and menarcheal age in 793 healthy term-born Swedish girls, a subset of the GrowUp1990Gothenburg cohort. The timing of menarche and postmenarcheal growth was related to variables from the Quadratic-Exponential-Pubertal-Stop (QEPS) growth model, birth characteristics, and parental height. Multivariable models were constructed for clinical milestones; at birth, age 7 years, pubertal growth onset, and midpuberty. Results: Menarche aligned with 71.6% (18.8) of the QEPS model's specific pubertal growth function, at a mean age of 13.0 (1.3) years, ranging from 8.2 to 17.2 years. Postmenarcheal growth averaged 8.0 (4.9) cm, varying widely from 0.2 to 31.1 cm, decreasing with later menarche. Significant factors associated with menarcheal age included height at 7 years, childhood body-mass index, parental height, and QEPS-derived pubertal growth variables. Multivariable models demonstrated increasing explanatory power for each milestone, explaining 1% of the variance in menarcheal age at birth, 8% at age 7 years, 44% at onset of pubertal growth, and 45% at midpuberty. Conclusions: This study underscores the strong link between pubertal growth and age at menarche. Data available at start of puberty explain 44% of the variation in menarcheal age, apparent on average 3.2 years before menarche. In addition, the study shows a previously seldom noticed wide variation in postmenarcheal height gain from 0.2 to 31.1 cm.

Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development.

Denys-Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development.

Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.

Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

Endocrine and metabolic aspects of narcolepsy type 1 in children.

STUDY OBJECTIVES: To study whether the onset of narcolepsy type 1 (NT1) in children and adolescents affects BMI, specific metabolic risk factors, the onset of puberty, longitudinal growth or other endocrine functions. METHODS: A population-based study, comprising 34 patients, was performed with a clinical evaluation, an assessment of puberty and growth, actigraphy and blood samples at fasting, from patients and controls, to evaluate pituitary function, growth factors, thyroid gland, gonads, insulin sensitivity, appetite regulation and blood lipids. RESULTS: In the post-H1N1 vaccination (PHV) narcolepsy group, the median BMI SDS was higher 6-12 months after the onset of narcolepsy (p < 0.01), but it was no different 10 years after the onset of narcolepsy (p = 0.91), compared with 12-24 months before the onset of narcolepsy. There was a correlation between an increase in BMI and a decrease in total energy expenditure (R = -0.74). In the nPHV group, weight and BMI changes were smaller and no significant changes were recorded. Early puberty was more common in patients with puberty onset after narcolepsy onset (n = 16/19) compared with patients with puberty onset before narcolepsy onset (n = 3/11, p = 0.02). There was no significant change in height SDS during the studied period. Although they were within normal ranges, both median HDL and median TSH levels were significantly lower in NT1 patients, compared with controls. CONCLUSIONS: We found a high prevalence of large BMI gain in the period immediately after the onset of narcolepsy, which had almost normalized at the long-term follow-up. The onset of narcolepsy led to early puberty in both sexes. Linear growth was not affected. We did not find any strong indicators of metabolic disturbances.

[Daytime sleepiness and cognitive disorders in elderly patients]. / Dnevnaia sonlivost' i kognitivnye rasstroistva v pozhilom vozraste.

Data on the contribution of daytime sleepiness to cognitive impairment in elderly patients are presented. Currently, diagnostic methods of daytime sleepiness, which include diaries, neurological, clinical and instrumental tools, are used. It has been shown that daytime sleepiness correlates with different types of dementia that suggests the involvement of common neurochemical mechanisms. Multiple studies report that daytime sleepiness increases the risk of dementia in elderly people. Future research of daytime sleepiness could be focused on its clinical and paraclinical presentations to facilitate the prognosis of dementia.

Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature.

CONTEXT: Weight-based GH dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS). OBJECTIVE: The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose. SETTING: A total of 153 short prepubertal children diagnosed with isolated GHD or ISS (n = 43) and at least 1 SD score (SDS) below midparental height SDS (MPH(SDS)) were included in this 2-yr multicenter study. INTERVENTION: The children were randomized to either a standard (43 microg/kg.d) or individualized (17-100 microg/kg.d) GH dose. MAIN OUTCOME MEASURE: We measured the deviation of height(SDS) from individual MPH(SDS) (diffMPH(SDS)). The primary endpoint was the difference in the range of diffMPH(SDS) between the two groups. RESULTS: The diffMPH(SDS) range was reduced by 32% in the individualized-dose group relative to the standard-dose group (P < 0.003), whereas the mean diffMPH(SDS) was equal: -0.42 +/- 0.46 and -0.48 +/- 0.67, respectively. Gain in height(SDS) 0-2 yr was equal for the GH-deficient and ISS groups: 1.31 +/- 0.47 and 1.36 +/- 0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24-h profile. CONCLUSION: Individualized GH doses during catch-up growth significantly reduce the proportion of unexpectedly good and poor responders around a predefined individual growth target and result in equal growth responses in children with GHD and ISS.

Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency.

CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden. INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS. RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.

Phenotypic persistence and external shielding ultraviolet radiation inactivation kinetic model.

AIM: To develop an inactivation kinetic model to describe ultraviolet (UV) dose-response behaviour for micro-organisms that exhibit tailing using two commonly referenced causes for tailing: physical shielding of micro-organisms and phenotypic persistence. METHODS AND RESULTS: Dose-response data for Escherichia coli, Mycobacterium terrae and Bacillus subtilis spores exposed to UV radiation were fit to the phenotypic persistence and external shielding (PPES) model. The fraction of persistent micro-organisms in the original population (N(persistent)/N(total)) that exhibited reduced sensitivity to UV radiation was estimated by the PPES model as approx. 10(-7), 10(-5) and 10(-4) for E. coli, B. subtilis spores and Myco. terrae, respectively. Particle shielding effects were evaluated for Myco. terrae and resulted in additional reduction in UV sensitivity. CONCLUSIONS: Tailing occurred in laboratory experiments even when clumping and shielding were eliminated as major factors in UV resistance, suggesting that phenotypic persistence in addition to shielding may be important to consider when evaluating dose-response curves for disinfection applications. SIGNIFICANCE AND IMPACT OF THE STUDY: The PPES model provides a mechanistically plausible tool for estimating the dose-response behaviour for micro-organisms that exhibit tailing in dispersed and aggregated settings. Accurate dose-response behaviour (including the tailing region) is critical to the analysis and validation of all UV disinfection systems.

Electrical detection of germination of viable model Bacillus anthracis spores in microfluidic biochips.

In this paper, we present a new impedance-based method to detect viable spores by electrically detecting their germination in real time within microfluidic biochips. We used Bacillus anthracis Sterne spores as the model organism. During germination, the spores release polar and ionic chemicals, such as dipicolinic acid (DPA), calcium ions, phosphate ions, and amino acids, which correspondingly increase the electrical conductivity of the medium in which the spores are suspended. We first present macro-scale measurements demonstrating that the germination of spores can be electrically detected at a concentration of 10(9) spores ml(-1) in sample volumes of 5 ml, by monitoring changes in the solution conductivity. Germination was induced by introducing an optimized germinant solution consisting of 10 mM L-alanine and 2 mM inosine. We then translated these results to a micro-fluidic biochip, which was a three-layer device: one layer of polydimethylsiloxane (PDMS) with valves, a second layer of PDMS with micro-fluidic channels and chambers, and the third layer with metal electrodes deposited on a pyrex substrate. Dielectrophoresis (DEP) was used to trap and concentrate the spores at the electrodes with greater than 90% efficiency, at a solution flow rate of 0.2 microl min(-1) with concentration factors between 107-109 spores ml(-1), from sample volumes of 1-5 microl. The spores were captured by DEP in deionized water within 1 min (total volume used ranged from 0.02 microl to 0.2 microl), and then germinant solution was introduced to the flow stream. The detection sensitivity was demonstrated to be as low as about a hundred spores in 0.1 nl, which is equivalent to a macroscale detection limit of approximately 10(9) spores ml(-1). We believe that this is the first demonstration of this application in microfluidic and BioMEMS devices.

Alterations of RNA metabolism in sea urchin embryos by an inhibitor of protein synthesis initiation.

An inhibitor of the initiation of protein synthesis, 2-(4-methyl-2,6 dinitroanilino)-N-methyl propionamide, (MDMP), inhibits incorporation of amino acids by 85--95% without altering the rate of incorporation of uridine into sea-urchin-hatched blastula embryos. Since the inhibition is readily reversible up to at least 90 min after addition, extensive secondary effects are unlikely. Newly synthesized RNA accumulates in polyribosome-like structures in amount and with a size distribution very similar to the control. The polyadenylation of total, cytoplasmic and polyribosomal RNA are only slightly different from the controls. While the size distribution of 9-S of approx. 30-S RNA is about the same, there is relatively less low molecular weight RNA (approx. 4-S). There is also a greater accumulation of greater than 30-S RNA in the cytoplasm of treated embryos due either to leakage and/or improper processing of nuclear RNA. The latter possibility is consistent with the decrease in 4-S RNA which is a presumed degradation product of nuclear HnRNA. While the initial rate of RNA synthesis and much of the accumulation of RNA in polyribosomes are not affected, the inhibition of protein synthesis per se or a secondary effect of MDMP results in altered patterns of RNA transport and processing.

Evaluation of a new defibrillation pathway: tongue-epigastric/tongue-apex route. II. Impedance characteristics in human subjects.

An automated device for defibrillation using a vertical shock pathway (tongue-epigastric or tongue-apex) has been developed. The energy requirements for defibrillation using vertical pathways are uncertain and will be determined largely by the impedance of the pathway. The purpose of this study was to determine the impedance characteristics of vertical defibrillation pathways in human subjects. Twenty patients undergoing elective cardioversion of atrial fibrillation or atrial flutter, or both, were studied. Patients received shocks from electrodes placed in tongue-epigastric or tongue-cardiac apex positions. The tongue electrode was a 12 cm2 metal plate fixed to a standard plastic oropharyngeal airway. The epigastric or cardiac apex electrode was a 40 cm2 self-adhesive pad. The electrodes were connected to a standard damped-sinusoidal waveform defibrillator. It was found that the two vertical shock pathways had substantially higher impedance than the standard transthoracic pathway: tongue-epigastric pathway 130 +/- 11 omega (SD), tongue-apex pathway 115 +/- 12 omega, transthoracic pathway 68 +/- 11 omega (p less than 0.05). The higher impedance is probably due to the longer interelectrode distances of vertical pathways: tongue-epigastric 33 +/- 3 cm, tongue-apex 28 +/- 3 cm, transthoracic 23 +/- 3 cm (p less than 0.05). Vertical pathway shocks were successful in the cardioversion of 15 of 20 patients. Four of the five patients in whom vertical shocks were unsuccessful subsequently underwent successful cardioversion by transthoracic shocks; the transthoracic shocks achieved a higher current because of lower impedance of the transthoracic route.(ABSTRACT TRUNCATED AT 250 WORDS)