Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease.

OBJECTIVES: To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease. METHODS: We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus. RESULTS: Forty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels. CONCLUSIONS: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.

Correction to: Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease.

Due to a typesetting error the wrong Table 2 was used. The correct Table 2 is shown here.

Little or no solar wind enters Venus' atmosphere at solar minimum.

Venus has no significant internal magnetic field, which allows the solar wind to interact directly with its atmosphere. A field is induced in this interaction, which partially shields the atmosphere, but we have no knowledge of how effective that shield is at solar minimum. (Our current knowledge of the solar wind interaction with Venus is derived from measurements at solar maximum.) The bow shock is close to the planet, meaning that it is possible that some solar wind could be absorbed by the atmosphere and contribute to the evolution of the atmosphere. Here we report magnetic field measurements from the Venus Express spacecraft in the plasma environment surrounding Venus. The bow shock under low solar activity conditions seems to be in the position that would be expected from a complete deflection by a magnetized ionosphere. Therefore little solar wind enters the Venus ionosphere even at solar minimum.

Single-chain antigen-binding proteins.

Single-chain antigen-binding proteins are novel recombinant polypeptides, composed of an antibody variable light-chain amino acid sequence (VL) tethered to a variable heavy-chain sequence (VH) by a designed peptide that links the carboxyl terminus of the VL sequence to the amino terminus of the VH sequence. These proteins have the same specificities and affinities for their antigens as the monoclonal antibodies whose VL and VH sequences were used to construct the recombinant genes that were expressed in Escherichia coli. Three of these proteins, one derived from the sequence for a monoclonal antibody to growth hormone and two derived from the sequences of two different monoclonal antibodies to fluorescein, were designed, constructed, synthesized, purified, and assayed. These proteins are expected to have significant advantages over monoclonal antibodies in a number of applications.

Mitochondrial cytochrome c release: a factor to consider in mitochondrial disease?

The pathogenesis of mitochondrial disorders has largely focused on the impairment of cellular energy metabolism. However, mitochondrial dysfunction has also been implicated as a factor in the initiation of apoptosis due to the translocation of cytochrome c, from mitochondria to the cytosol, and the subsequent cleavage of pro-caspase 3. In this study, we determined the cytochrome c content of cytosols (skeletal muscle) prepared from 22 patients with evidence of compromised mitochondrial electron transport chain enzyme activity and 26 disease controls. The cytochrome c content of the mitochondrial electron transport chain-deficient group was found to be significantly (p < 0.02) elevated when compared with the control group (63.7 +/- 15.5 versus 27.7 +/- 2.5 ng/mg protein). Furthermore, a relationship between the cytosolic cytochrome c content of skeletal muscle and complex I and complex IV activities was demonstrated. Such data raise the possibility that mitochondrial cytochrome c release may be a feature of mitochondrial disorders, particularly for those patients with marked deficiencies of respiratory chain enzymes. Whether initiation of apoptosis occurs as a direct consequence of this cytochrome c release has not been fully evaluated here. However, for one patient with the greatest documented cytosolic cytochrome c content, caspase 3 could be demonstrated in the cytosolic preparation. Further work is required in order to establish whether a relationship also exists between caspase 3 formation and the magnitude of respiratory chain deficiency.

Cognitive ability is associated with suspected reporting errors on food frequency questionnaires.

OBJECTIVE: To examine potential for bias in reported total energy intake on a Food Frequency Questionnaire (FFQ) among older adults. DESIGN: Longitudinal cohort study. SUBJECTS/SETTING: 2,706 Community-dwelling Black and White older adults, aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Multivariate logistic regression analyses were conducted with potential errors on reported total energy intake on the Food Frequency Questionnaire (FFQ) as the outcome variable and with cognitive ability, measured by the Modified Mini Mental State Exam (3MS) as the primary independent variable. The regression model controlled for site, race, gender, age, body size, and physical activity. Separate models were fit using 3MS as a continuous variable and for multiple 3MS cutpoints. All models revealed similar findings. RESULTS: Cognitive ability was inversely associated with potential errors in reporting total energy intake, whereby a five-point increase in 3MS scores was associated with a 14% decreased likelihood of reporting errors (Odds Ratio=0.86, 95% Confidence Interval: 0.77, 0.95). Additionally, compared to White women, White men were 2 times more likely, and Black women and Black men were 3 times more likely, to have errors in reporting total energy intake. CONCLUSION: This study provides evidence that for older adults, lower cognition scores are associated with increased potential errors in reporting total energy intake. APPLICATIONS: Dietary reporting from older adults may be inaccurate due to cognitive deficits. A brief assessment of cognitive function may assist clinicians in dietary evaluations and recommendation and may benefit studies using FFQ data where the measure of cognitive function could be utilized to stratify data analyses and conduct sensitivity analyses.

Body image, mood and quality of life in young burn survivors.

This study looks at the body image, mood and quality of life of a group of 36 young people aged between 11 and 19 years who had burns as children, compared with an age-matched control group of 41 young people who had not had these injuries. Participants completed the Body Esteem Scale (BES), the Satisfaction With Appearance Scale (SWAP), the Beck Depression Inventory-II (BDI-II) and the Youth Quality of Life Questionnaire (YQOL). It was hypothesised that young burn survivors would report more dissatisfaction with their appearance, a lower mood and a lower quality of life compared with non-injured controls. However, young burn survivors reported significantly more positive evaluations of how others view their appearance (p=0.018), more positive weight satisfaction (p=0.001) and a higher quality of life (p=0.005) than the control group. They also reported more positive general feelings about their appearance, although this was just below the level for statistical significance (p=0.067) and a similar mood to the school sample (p=0.824). The data suggest that young burn survivors appear to be coping well in comparison to their peers, and in some areas may be coping better, in spite of living with the physical, psychological and social consequences of burns.

In vivo tumor targeting of a recombinant single-chain antigen-binding protein.

We describe here the first in vivo targeting of tumors with a single-chain antigen-binding protein. The molecule, which was constructed and expressed in Escherichia coli, is a novel recombinant protein composed of a variable light-chain (VL), amino acid sequence of an immunoglobulin tethered to a variable heavy-chain (VH) sequence by a designed peptide. We show that this protein, derived from the DNA sequence of the variable regions of the antitumor monoclonal antibody B6.2, has the same in vitro antigen-binding properties as the B6.2 Fab' fragment. Comparative pharmacokinetic studies in athymic mice demonstrate much more rapid alpha and beta phases of plasma clearance for the single-chain antigen-binding protein than for the Fab' fragment, as well as an extremely rapid whole-body clearance. Half-life values for alpha and beta phases of single-chain antigen-binding protein clearance were 2.4 minutes and 2.8 hours, respectively, versus 14.8 minutes and 7.5 hours for Fab'. Furthermore, the single-chain antigen-binding protein molecule did not show accumulation in the kidney as did the Fab' molecule or, as previously shown, the F(ab')2 molecule. Despite its rapid clearance, the single-chain antigen-binding protein showed uptake in a human tumor xenograft comparable to that of the Fab' fragment, resulting in tumor to normal tissue ratios comparable to or greater than those obtained with the Fab' fragment. These studies thus demonstrate the in vivo stability of recombinant single-chain antigen-binding proteins and their potential in some diagnostic and therapeutic clinical applications in cancer and other diseases.

Estimating the body temperature of groups of pigs by thermal imaging.

Measurements on 28 pens of pigs containing 384 animals to be slaughtered at a commercial abattoir showed that the mean ear temperatures of the pigs in each pen, measured with a thermal imaging camera, were significantly correlated (r=0.71, P<0.001) with the mean temperature of the blood the pigs lost at exsanguination. In measurements on 220 pigs in 16 of the 28 pens, the mean activity of serum creatine kinase was positively correlated with the mean ear temperature (r=0.55, P<0.05) and the mean concentration of serum cortisol was positively correlated with the mean blood temperature (r=0.50, P<0.05), suggesting that the hotter pigs were suffering from a higher level of stress.

Comparison of the effects of fan-assisted and natural ventilation of vehicles on the welfare of pigs being transported to slaughter.

A total of 417 pigs with an estimated average liveweight of 91 kg were transported to slaughter in three journeys, carried out in late June, each consisting of a three-hour drive followed by a one-hour holding period at the slaughter plant before they were unloaded. The pigs were accommodated on the lower two decks of a three-deck articulated lorry, each deck having five equal-sized pens; half were kept in naturally ventilated pens and half in pens with fan-assisted ventilation. The pigs' body temperature was recorded as the temperature of the blood lost at exsanguination, and as the temperature of the inner surface of the ear measured by thermal imaging. The pigs carried on the upper deck were hotter than those carried on the lower deck, and the pigs carried at the front of the vehicle were hotter than those at the back. There were small differences between the temperatures of the pigs in the different pens, but overall the temperatures of the pigs kept in pens with fan-assisted ventilation were no lower than those of the pigs kept in pens with natural ventilation. The higher temperature of the pigs transported in the front of the vehicle was associated with significantly higher serum concentrations of cortisol and activities of creatine kinase, and a tendency to higher albumin concentrations and osmolality, suggesting that they may have been exposed to more physical and psychological stress, and were possibly slightly more dehydrated, than the pigs in the rearmost pens. The type of ventilation had no effect on the blood composition of the pigs.

Cost-effectiveness of clozapine monitoring after the first 6 months.

BACKGROUND: Clozapine is effective in treating patients with schizophrenia who do not respond to conventional neuroleptic drugs. The drug is unique in that it is available only with a US Food and Drug Administration-mandated system for weekly monitoring of patients' white blood cell counts. No study has been conducted to evaluate the cost-effectiveness of this mandatory monitoring system. METHODS: A benchmark case was established by utilizing cumulative incidence rates of agranulocytosis from a recent study with a large sample of clozapine-treated patients. We assumed a 20% mortality among patients with agranulocytosis, $30.61 in monitoring costs each week, and 14.4 years of remaining life expectancy after detection of agranulocytosis. Based on these bench-mark assumptions, cost-effectiveness ratios in dollars per quality-adjusted life-year were calculated for the first, second, and third 6-month periods during which a patient was receiving clozapine. Sensitivity analyses were performed with more conservative assumptions in 5 alternative scenarios. RESULTS: In the benchmark case, costs per quality-adjusted life-year gained were $61,694, $925,418, and $420,644 for the first, second, and third 6-month periods of clozapine treatment, respectively. In the alternative scenarios, these costs ranged from $7923 to $46,056 for the first 6-month period and from $54,025 to $690,850 for the second and third 6-month periods. CONCLUSIONS: While the costs of monitoring patients with schizophrenia in the first 6-month period of clozapine treatment seem to be justifiable, monitoring thereafter may not be cost-effective because of the very low incidence of agranulocytosis in the later periods.

Relationship between perceived self-control of pain, pain description and functioning.

Recent research has shown an association between preferred coping style and pain report. The present study explores in a sample of 51 patients with chronic pain of myofascial origin the relationship between a dispositional measure of coping, the internality dimension of the Pain Locus of Control Scale (PLOC), and ratings of pain intensity, frequency, and pain-related behavioral functioning. Patients above the median on the internality dimension of the PLOC reported their pain as less intense and frequent than those below the median. No differences were noted on the behavioral functioning measures. Results are consistent with previous studies and indicate an association between ability to control pain and variations in magnitude and periodicity of pain. The clinical implication of the data is that strategies which provide reduction in pain intensity and frequency might be expected to result in increased perception of personal control of pain.

Patterns of smokeless tobacco use by young adolescents.

The use of smokeless tobacco products by adolescents has reportedly increased. The purpose of this study was to examine the use of smokeless tobacco by young adolescents across geographic locations and to look at patterns of use and variables associated with continued use beyond experimentation. Participants were 2018 students in sixth through ninth grades. Forty-five percent were male and 76% were white. Use of smokeless tobacco products was reported by 12% of the total population, and 25% reported smoking. Smokeless tobacco use was associated with cigarette smoking, alcohol use, and parental substance abuse. Those reporting alcohol use were more than four times more likely to be users of smokeless tobacco than nondrinkers. We found increased age, being male, being white, smoking, drinking, perceived effects of smokeless tobacco use, and friends' smoking behavior to be significantly associated with continued use beyond experimentation. Smokeless tobacco use was reportedly greater in rural areas. Adolescents who reported initiating use between 6 and 8 years of age were using on a more frequent basis than those who had initiated use when older. This study demonstrated the need for targeting elementary schools for educational interventions aimed at reducing smokeless tobacco use.

Increased plasma levels of pancreatic polypeptide and decreased plasma levels of motilin in encopretic children.

OBJECTIVE: Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. METHODS: Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. RESULTS: Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P < .05) for encopretic patients. The motilin response was lower (P < .03) for encopretic children than for controls. CONCLUSIONS: We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Risk factors and outcomes for failure to thrive in low birth weight preterm infants.

OBJECTIVE: To determine the epidemiology, clinical characteristics, and outcomes for low birth weight (LBW) infants with growth deficiency, or failure to thrive (FTT, the term commonly used by pediatric providers to describe growth deficiency or faltering in early childhood). DESIGN: Three-year prospective cohort study with matched case-control study of outcomes. SETTING: Eight large university hospital sites throughout the United States. SAMPLE: 914 LBW infants inborn at the sites and meeting study criteria. RESULTS: FTT was a common condition in this cohort, with 180 (19.7%) of 914 LBW infants meeting case criteria by 30 months. New cases of FTT peaked at 8 months gestation-corrected age. In addition to expected differences in growth between infants with and without FTT, infants with FTT had lower developmental indices and less stimulating home environments. At 36 months, FTT infants had lower IQ scores and were much smaller than infants without FTT. CONCLUSIONS: Growth deficiency, or FTT, is a common clinical condition for those involved in the follow-up care of LBW infants. Worse cognitive and growth outcomes were observed for those meeting the restrictive case criteria employed in this study. More than 80% of the cases in this LBW cohort did not involve any chronic medical disorders, but several biological and environmental differences were found between those who developed FTT and those who did not.

Quid significat nomen? (What's in a name?).

For the purposes of classification and effective communication among scientists, organisms must have unequivocal names. The binomial naming system of species was devised and popularized by Linnaeus in the 18th Century. His "Botanical Latin" is an artificial language first adopted for naming plants and is now internationally accepted as a naming system for both plants and animals. Genus and species names are based on Latin and Greek words which describe characteristics of the organism, as well as words from more modern sources, such as the name of the discoverer or place of discovery. Naming follows certain rules and all of the word endings are Latinized. The history of naming parasites is interesting and the molecular age may influence naming in the future.

Trixacarus caviae infection of guinea pigs with genetically determined differences in susceptibility to Trichostrongylus colubriformis infection.

Guinea pigs with genetically determined resistance or susceptibility to infection with the nematode parasite Trichostrongylus colubriformis were allowed to become infected with the sarcoptid mite Trixacarus caviae. Compared with nematode-susceptible guinea pigs, nematode-resistant animals had larger populations of mites and developed a more severe dermatitis, with greater mast cell hyperplasia and many more infiltrating eosinophils. The results suggest that animals bred for resistance to one parasite may have greater susceptibility to other parasites.

Malformations and minor anomalies in non-trisomic, autosomal aneuploidy.

We examined the medical records of 43 individuals with non-trisomic, autosomal aneuploidy evaluated by the Arkansas Genetics Program. Birthweight and the presence of malformations and minor anomalies by organ system were analyzed on each patient. Low birthweight was present in 28% (N = 12) of the patients, 72% (N = 31) of the subjects had a malformation, and 93% (N = 40) had a minor anomaly. Of the entire sample, the most common site of a malformation or minor anomaly was the limbs (79%). The most common site of a malformation was the head (21%), eyes (21%), or heart (26%). If a malformation was present, the head was significantly more likely (P < .04) than another body system to be the site of an additional malformation or minor anomaly. A malformation or minor anomaly of the ears was significantly more likely (P < .03) to be present when there was an associated eye anomaly than when no anomaly of the eye was identified. These data have implications for chromosome screening of individuals with malformations or minor anomalies and for the clinical evaluation of those found to have non-trisomic autosomal aneuploidy.

The effect of on-site extracorporeal membrane oxygenation on the therapy choice and outcomes of neonates with persistent pulmonary hypertension.

The effect of on-site extracorporeal membrane oxygenation (OS-ECMO) and selection criteria on the utilization rate of this technology is unknown. We retrospectively studied 55 neonates who were admitted to Arkansas Children's Hospital from 1985 to 1993. We compared the ECMO utilization, mortality, and morbidity rates for outborn neonates with moderate and severe persistent pulmonary hypertension (PPHN) before and after the establishment of an ECMO program with guidelines for its use at our institution. The rate of ECMO use was three times higher and the mortality rate was 13 times lower in the period after OS-ECMO compared with the period when ECMO was available only at other institutions. No differences were observed in the morbidity rates between the two periods. Physician decisions to initiate ECMO involved more than guidelines, since 37% of the increased ECMO use was not associated with use of the guidelines. Possible reasons for noncompliance with the guidelines are discussed. Neonates who had received medical therapy only and who had an oxygenation index > or = 30 and < 40 had no mortality. Our findings suggest that the need for ECMO in this group of neonates is low.

Intensive short course chemotherapy for tuberculous meningitis.

This nonrandomized, open clinical investigation of tuberculous meningitis evaluated 53 children with Stage I (n = 8), Stage II (n = 29) and Stage III (n = 16) disease. The overall mortality was 20.8% (11 of 53) with a rate of sequelae of 35.7% (15 of 42) in survivors reflecting the advanced stages of children at diagnosis. Various combinations of standard antituberculous drugs including isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol were given. Three treatment durations used during various time periods were evaluated: 12, 9 and 6 months with only the 6-month regimen receiving pyrazinamide (PZA). This prospective evaluation demonstrated that: (1) severe disease at presentation is highly associated with early mortality (P less than 0.05), regardless of drug regimen; and (2) intensive short course chemotherapy (6 months) with PZA, regardless of stage of disease at presentation, is more efficacious than longer course therapy (9 or 12 months) without PZA in preventing total negative outcomes and sequelae (P less than 0.05). This study demonstrates that a 6-month regimen containing PZA can be used in treating children with tuberculous meningitis.