Rapid assessment of the geographical distribution of Mansonella perstans infections in Uganda, by screening schoolchildren for microfilariae

The geographical distribution of Mansonella perstans infections in Uganda was assessed by day-time examination of school-aged children for microfilariae. Overall, 12,207 children from 76 sites representing the various topographical and ecological zones in the country were examined. Children with M. perstans microfilaraemia were detected at 47 (61.8%) of the study sites, with prevalences ranging from 0.4% to 72.8%. A broad, east-west-oriented belt of high endemicity was identified, stretching across the central part of the country from the southern end of Lake Albert to the north-western shores of Lake Victoria. To the north and south of this belt prevalences generally decreased, although high-prevalence foci were also identified in the far north-western and south-eastern corners of the country. Geostatistical interpolation was used to create a map showing the geographical distribution of M. perstans prevalences in Uganda (by ordinary kriging), and to assess the population exposed to M. perstans transmission. Estimates based on population data from 2002 indicated that 20.4 million people (82.6% of the national population) and 6.8 million people (27.5% of the national population) lived in areas where, respectively, >1% and >10% of the school-aged children had M. perstans microfilaraemias. Since the prevalence of M. perstans microfilaraemia is known to increase with age, the overall population prevalences are likely to be even higher than the prevalences observed in the school-aged children. More attention needs to be paid to the public-health implications of this wide-spread but neglected infection.     

Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) linked to the spastic gait gene 4 (SPG4) is controversial, as the "pure" form traditionally has been considered confined to the long axons of the spinal cord. However, recent immunolabeling experiments have demonstrated extensive Spastin expression in the cortex and striatum. This could indicate a more widespread neuropathology from mutations in the SPG4 gene than previously assumed. The aim of this study was therefore to ascertain the extent of cerebral involvement in SPG4 linked HSP by neuropsychological examination and measurement of the regional cerebral blood flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using Statistical Parametric Mapping (SPM 99). Neuropsychological assessment was performed using established and nationally validated tests (RH Basic Battery). Compared to healthy controls, the patient group had significantly decreased rCBF in the left fronto-temporal cortex (P<0.05), and more extensive changes were observed in a separate analysis of the most disabled individuals. The neuropsychological assessment revealed only significantly impaired recognition memory for faces. In summary, the findings support cerebral pathology in SPG4-linked HSP, although the decreased rCBF in fronto-temporal cortex was not associated with severe cognitive impairment.     

Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations

Chorionic gonadotropin (CG) is an essential signal in establishment and maintenance of pregnancy in humans and higher primates. A G-to-A transition in exon 3 of human CGbeta gene 5, changing the naturally occurring valine residue to methionine in codon 79 (Val(79)Met) has been reported at carrier frequency 4.2% in a random population from the Midwest of the United States. The biological activity of the variant hCG was similar to that of wild-type (WT) hCG. However, the Val(79)Met beta-subunit displayed impaired ability to assemble with alpha-subunit, and the amount of hCG alpha/beta heterodimers formed and secreted by transfected cells was seriously impaired in the previous study. Because of these functional implications we found it important to study the occurrence of the Val(79)Met hCGbeta variant in other populations. By using a PCR-RFLP method, a search for the Val(79)Met hCGbeta variant was carried out on a total of 580 DNA samples from five European populations (Finland, Denmark, Greece, Germany and the UK). The results demonstrated an absence of the polymorphism in these populations. Hence, the naturally occurring variant (Val(79)Met) of the hCGbeta gene 5, found previously at high frequency in the US, is clearly less common, or absent, in the European populations studied.     

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo

Rationale The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered.Objective This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo.Methods Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers (n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo.Results Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response.Conclusions Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.     

Hypoglycaemia and elevated urine ethylmalonic acid in a child homozygous for the short-chain acyl-CoA dehydrogenase 625G > A gene variation

The aim of this case report is to call attention to short-chain acyl-CoA dehydrogenase (SCAD) deficiency as a possible contributory factor to hypoglycaemia in childhood. We report on a previously healthy 14 mo-old Danish boy who presented with hypoglycaemia and metabolic acidosis after a few days of upper airway infection. After two days on a normal diet, he recovered clinically and biochemically. A thorough biochemical examination did not reveal the cause of the hypoglycaemia. However, the excretion of ethylmalonic acid in two morning urine samples was moderately increased, and hence the SCAD gene was screened for mutations. We found the child homozygous for the G > A SCAD gene variation at position 625. Conclusion: In this patient, reduced function of the SCAD protein is reflected in the excretion of ethylmalonic acid, a marker of intracellular accumulation of butyryl-CoA and the cytotoxic butyric acid. Furthermore, gluconeogenesis might be compromised owing to lack of reducing equivalents from the oxidation of short-chain fatty acids in the fasting or stressed state, thus contributing to the predisposition for fasting hypoglycaemia.     

Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study

BACKGROUND: Classic galactosemia (OMIM 230400) is an inherited disorder in the metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate uridyl transferase (EC 2.7.7.12). Galactosemia leads to accumulation of galactose and galactose 1-phosphate (gal-1-P) in blood and tissues and, if untreated, produces neonatal death or severe mental retardation, cirrhosis of the liver, and cataracts. Hence, the disorder is included in many neonatal screening programs. METHODS: We retrospectively analyzed filter-paper blood samples obtained 4-8 days postpartum for routine neonatal screening from 12 galactosemia patients and 2055 random controls. Total hexose monophosphates (HMPs) were used as a marker of gal-1-P and were assayed by negative-ion mode electrospray tandem mass spectrometry (tandem MS) with settings biased toward gal-1-P detection. The predominant precursor/product ion pair m/z 259/79 was used to quantify total HMPs by external standardization. RESULTS: Linear calibration curves were obtained in the range 0-8 mmol/L gal-1-P. The detection limit was 0.1 mmol/L HMP, and total CVs ranged from 13% at the detection limit to <8% at >1 mmol/L HMP. The method was in agreement with an alkaline phosphatase-galactose dehydrogenase method. All samples from galactosemia patients contained increased HMP concentrations (range for patients, 2.6-5.2 mmol/L; range for reference group, <0.10-0.94 mmol/L). The diagnostic sensitivity and specificity were 100% at a cutoff of 1.2 mmol/L HMP. A Duarte/classic galactosemia compound heterozygous sample could be discriminated clearly from both patient and reference samples. CONCLUSION: Quantitative analysis of HMPs by tandem MS can be used in laboratory investigations of galactosemia.     

Plasma N-terminal proatrial natriuretic factor can predict normal pulmonary capillary wedge pressure in cardiac transplant recipients

BACKGROUND: Plasma N-terminal proatrial natriuretic factor (proANP) is closely related to atrial filling pressure, but this may be distorted in heart transplant recipients. OBJECTIVE: The aim of this study was to examine the usefulness of proANP as a non-invasive marker of cardiac filling pressure in transplanted patients with normal to moderately elevated serum creatinine (s-creatinine). METHODS: Blood was sampled at rest for analysis of proANP from 220 patients 1-13 (median 4) years after orthotopic heart transplantation undergoing routine diagnostic catheterization. RESULTS: In multivariate analysis proANP was significantly positively related to s-creatinine, mean pulmonary capillary wedge pressure (PCWP) and time after transplantation and negatively related to haemoglobin and cardiac index. All the patients with proANP below 1140 pmol/l had normal PCWP (<13 mmHg). The area under the receiver-operating characteristic curve for proANP for the detection of PCWP > 13 mmHg was 0.81. The positive predictive value of proANP for detection of increased PCWP was very low. CONCLUSION: A low proANP had a 100% negative predictive value for increased atrial pressure but the low positive predictive value makes proANP unsuitable as an indicator of increased atrial pressures in heart transplanted patients.