Salbutamol for hyperkalaemia in children

Hyperkalaemia is a potentially fatal disorder that demands direct treatment. The efficacy of traditional medical treatment is unpredictable, limited, of short duration or carries the risk of serious adverse events. The administration of salbutamol for hyperkalaemia in children is described in several clinical trials and case reports.

Conclusion: Salbutamol, inhaled or infused, is safe and efficacious and results in a predictable and long-lasting reduction in serum potassium. Salbutamol merits a place as the preferred medication for hyperkalaemia in children without arrhythmias. If follow-up with haemodialysis is required, the administration of salbutamol gives time to make the necessary preparations.     

Anti‐infliximab antibody status and its relation to clinical response in psoriatic patients: A pilot study

Although the mechanisms underlying the loss of response to infliximab are not completely understood, the formation of antibodies to infliximab (ATI) are thought to play a role. The aim of this study was to investigate the presence of ATI in psoriatic patients and to evaluate its relationship to the clinical response. Fifteen patients with psoriasis were treated with infliximab (5 mg/kg) every 8 weeks after an initial three‐dose induction treatment. An enzyme linked immunosorbent assay kit was used for analyzing the presence of ATI in sera. Effectiveness assessments included the change in Psoriasis Area and Severity Index (PASI) compared with study entry. Five (33.3%) patients developed ATI. While 5.9 ± 3.2 infliximab infusions achieved a fall in the PASI score from a mean of 20.4 ± 8.3 to 5.3 ± 2.4 in ATI‐negative patients, these values changed from 23.3 ± 11 to 10 ± 4.9 after 9 ± 5.2 infusions in ATI‐positive patients. Our results suggested that ATI measured in psoriatic patients are of clinical importance. Therefore, monitoring for the induction of ATI and rescue strategies should be developed to avoid or to maintain a delay in ATI development.     

Long-term results of surgical treatment for pulmonary valve stenosis

109 children who survived surgical treatment for isolated pulmonary valve stenosis were followed for up to 17 years. In all the postoperative status was assessed as satisfactory. Cardiac catheterization repeated in 43 gave a resting valve gradient below 40 mmHg. The 22 children whose pulmonary valves had been excised were as healthy as the 87 who had undergone pulmonary valvotomy. Consideration was given to the desirable length of postoperative review. Except for the few children with symptoms before operation, a postoperative increase in exercise tolerance was not a feature.     

RP1 protein truncating mutations predominate at the RP1 adRP locus

PURPOSE: Recent reports have shown that the autosomal dominant retinitis pigmentosa (adRP) phenotype linked to the pericentric region of chromosome 8 is associated with mutations in a gene designated RP1. Screening of the whole gene in a large cohort of patients has not been undertaken to date. To assess the involvement and character of RP1 mutations in adRP, the gene was screened in a panel of 266 unrelated patients of British origin and a Pakistani family linked to this locus. METHODS: Patients exhibiting the adRP phenotype were screened for mutations in the four exons of the RP1 gene by heteroduplex analysis and direct sequencing. Linkage of the Pakistani family was achieved using microsatellite markers. Polymerase chain reaction (PCR) products were separated by nondenaturing polyacrylamide gel electrophoresis. Alleles were assigned to individuals, which allowed calculation of LOD scores. Microsatellite marker haplotyping was used to determine ancestry of patients carrying the same mutation. RESULTS: In the 266 British patients and 1 Pakistani family analyzed, 21 loss-of-function mutations and 7 amino acid substitutions were identified, some of which may also be disease-causing. The mutations, many of which were deletion or insertion events, were clustered in the 5' end of exon 4. Most mutations resulted in a premature termination codon in the mRNA. Haplotype analysis of nine patients carrying an R677X mutation suggested that these patients are not ancestrally related. CONCLUSIONS: RP1 mutations account for 8% to 10% of the mutations in our cohort of British patients. The most common disease-causing mechanism is deduced to be one involving the presence of a truncated protein. Mutations in RP1 have now been described in adRP patients of four ethnically diverse populations. The different disease haplotype seen in the nine patients carrying the same mutation suggests that this mutation has arisen independently many times, possibly due to a mutation hot spot in this part of the gene.     

Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa (RP), the commonest form of inherited retinal dystrophies is a clinically and genetically heterogeneous disorder. It is characterized by progressive degeneration of the peripheral retina leading to night blindness and loss of peripheral visual field. RP is inherited either in an autosomal dominant, autosomal recessive or X-linked mode. A locus (RP18) for autosomal dominant RP was previously mapped by linkage analysis in two large pedigrees to chromosome 1p13-q21. The human HPRP3 gene, the orthologue of the yeast pre-mRNA splicing factor (PRP3), localizes within the RP18 disease interval. The recent identification of mutations in human splicing factors, PRPF31 and PRPC8, led us to screen HPRP3 as a candidate in three chromosome 1q-linked families. So far, two different missense mutations in two English, a Danish family and in three RP individuals have been identified. Both mutations are clustered within a two-codon stretch in the 11th exon of the HPRP3 gene. Interestingly, one of the mutations (T494M) is seen repeatedly in apparently unlinked families raising the possibility of a mutation hot spot. This has been confirmed by haplotype analysis using SNPs spanning the HPRP3 gene region supporting multiple origins of the mutation. The altered HPRP3 amino acids, which are highly conserved in all known HPRP3 orthologues, indicate a major function of that domain in the splicing process. The identification of mutations in a third pre-mRNA splicing factor gene further highlights a novel mechanism of photoreceptor degeneration due to defects in the splicing process.     

Importance of nitric oxide in hepatic arterial blood flow and total hepatic blood volume regulation in pigs

The importance of nitric oxide in regulating basal arterial blood flow has been examined in several different vascular beds by intra-arterial infusion of inhibitors of nitric oxide synthesis, but not in the arterial vascular bed of the liver. In the present study, N^G-nitro-L -arginine (L -NNA), in a dose of 0.5 and 1.0 μmol mL^?1 of hepatic arterial blood flow, was infused for 5 min into the hepatic artery in seven pigs anaesthetized with pentobarbital sodium. The haemodynamic effects observed by the first infusion were not further enhanced by the second infusion. Hepatic arterial resistance increased by 143 ± 38% and hepatic arterial blood flow declined by 38 ± 10%. A systemic effect due to `spillover' was observed, as evidenced by an increase in mean aortic blood pressure of 24 ± 4 mmHg. However, no significant increase in arterial mesenteric resistance was observed and total liver blood flow remained unchanged. Hepatic arterial vasodilation in response to occlusion of the portal vein, the arterial buffer response, remained intact after inhibition of nitric oxide synthesis. Liver lobe thickness, measured by an ultrasonic technique,was not found to change with inhibition of arterial nitric oxide synthesis, excluding a significant direct effect of arterial nitric oxide on liver capacitance. In conclusion, nitric oxide is an important regulator of hepatic arterial resistance, but does not mediate the hepatic arterial buffer response and was not found to play any significant role in total hepatic capacitance regulation.     

A high resolution CEPH crossover mapping panel and integrated map of chromosome 11

High resolution (0.1 cM) CEPH crossover mapping panels were constructed for chromosome 11. These panels will facilitate a transition from top- down physical and genetic mapping strategies to integrated breakpoint mapping strategies. Novel methods, which differ from other methods in overcoming the limitations of incomplete heterozygosity and variable marker density, were developed for creating the panels and integrated maps. This made it possible to identify and sublocalize the majority of crossovers in 61 families. The panels were used to map 139 microsatellite markers. A semi-integrated map and a fully-integrated map were constructed by combining these data with data from CEPH 7.1 and then integrating data from the radiation hybrid (RH) map. Genetic lengths estimated from the mapping panels were similar to the estimates obtained when all recombinant and non-recombinant offspring were included (189.4 cM in females and 126.1 cM in males), indicating that genetic distances are stable at this high marker density. The maps have a cM density of 0.62. The distance between ordered markers is 1.39-2.92 cM depending on the criterion for order and the extent of map integration. The 2D maps provide the resolution and flexibility needed to enhance current applications such as positional cloning and mapping complex disorders; while the mapping panels will greatly improve the resolution, reliability and efficiency of future genetic mapping.      

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E₂ (PGE₂). In the first group, intravenous infusion of ANF (50 ng min^-1kg^-1body wt) reduced basal PGE₂ release from 4.4 ± 0.8 pmol min^-1to 1.8 ± 0.7 pmol min^-1. In the second group, intrarenal infusion of an α-adrenoceptor agonist, phenylephrine (2.5–6.75 μg min^-1), raised PGE₂ release from 2.7 ± 0.5 pmol min^-1to 7.5 ± 1.3 pmol min^-1. During continuous α₁-adrenergic stimulation, intravenous infusion of ANF (100 ng min^-1kg^-1body wt) reduced PGE₂ release to 3.5 ± 1.0 pmol min^-1. These results demonstrate that ANF reduces basal and α₁-adrenergic stimulated renal PGE₂ release.     

天水饮治疗中风急性期疗效观察

目的 :观察中药天水饮治疗中风急性期的疗效。方法 :将 93例中风急性期患者随机分成 2组 ,2组一般治疗相同 ,治疗组 62例加用天水饮 ,病程 1周内每日 2剂 ,1周后每日 1剂。对照组 3 1例加用尼可林 0 .5 g静滴及 2周内加用 2 0 %甘露醇静滴 ,2周后加服步长新脑心通治疗。 2组治疗 3 0日后进行疗效比较。结果 :治疗组愈显率为 79.0 4 % ,病程 10日内见效率为 62 .90 % ;对照组愈显率为 5 1.61% ,病程 10日内见效率为3 8.71% ,2组比较均有显著性差异 ( χ2 =7.3 9,P<0 .0 1和 χ2 =4 .88,P<0 .0 5 )。结论 :天水饮可改善病变区脑循环 ,增强脑细胞活力 ,促进语言及肢体功能恢复 ,对中风急性期有良好的疗效