Changing pattern of primary hyperoxaluria in Switzerland

Background The clinical course of primary hyperoxaluria (PH) is greatly variable and diagnosis is often delayed. Little is known about the overall occurrence and current prognosis. Methods We evaluated all known patients with PH residing and observed in Switzerland during the last 15 years with the help of a survey among Swiss nephrologists. Results Of the 25 patients observed between 7/79 and 6/94 in Switzerland, 18 were alive in 1994—14 on conservative therapy and four on renal replacement therapy (RRT). Twenty-two patients had PH type 1; the exact type was not determined in three. The estimated prevalence of PH (type 1) is 2 per million population; the minimal incidence is 1 per 100000 live births. Diagnosis was delayed by 8 years (median) except in infants. Five patients were pyridoxine sensitive. According to life table analysis, 20% of patients were in end-stage renal failure (ESRF) and 10% had died by the age of 15 years, and 50% were in ESRF and 20% dead at 25 years. Prognosis has improved: Five of 13 patients died during the first half of the observation period as opposed to two of 20 in the second part. Conclusions Overall prognosis appears better than hitherto believed considering the large clinical spectrum of PH. Greater awareness of PH is needed to improve further long-term prognosi

Efficacy of oral citrate administration in primary hyperoxaluria

Urinary citrate is a potent inhibitor of calcium oxalate (CaOx) crystallization, but oral citrate has rarely been used in patients with primary hyperoxaluria (PH). We studied the effect of sodium citrate administration (0.1-0.15 g/kg/day) on urinary citrate excretion and CaOx saturation in seven paediatric patients and the clinical response to long-term treatment (average 4 years) in five patients. Urinary citrate increased from 0.73 to 2.54 mmol/24h/l.73 m2 and urinary saturation for CaOx (calculated by equil 2) decreased from 11.41 to 6.79 (for both, p<0.02). Long-term administration of alkali citrate [0.15 g (0.5 mmol)/kg/day] resulted in stable or improved renal function in three and slow deterioration in two partially non-compliant patients. Alkali citrate is effective in patients with P

TricycloDNA-modified oligo-2′-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues—a comparative study of oligonucleotide length, design and chemistry

We report the evaluation of 20-, 18-, 16- and 14-mer phosphorothioate (PS)-modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in Tm, cell culture and animal experiments and compare them to their gap-matched 20-mer 2′-O-methoxyethyl (MOE) and 14-mer 2′,4′-constrained ethyl (cEt) counterparts. The sequence-matched 20-mer tcDNA and MOE ASOs showed similar Tm and activity in cell culture under free-uptake and cationic lipid-mediated transfection conditions, while the 18-, 16- and 14-mer tcDNA ASOs were moderate to significantly less active. These observations were recapitulated in the animal experiments where the 20-mer tcDNA ASO formulated in saline showed excellent activity (ED50 3.9 mg/kg) for reducing SR-B1 mRNA in liver. The tcDNA 20-mer ASO also showed better activity than the MOE 20-mer in several extra-hepatic tissues such as kidney, heart, diaphragm, lung, fat, gastrocnemius and quadriceps. Interestingly, the 14-mer cEt ASO showed the best activity in the animal experiments despite significantly lower Tm and 5-fold reduced activity in cell culture relative to the 20-mer tcDNA and MOE-modified ASOs. Our experiments establish tcDNA as a useful modification for antisense therapeutics and highlight the role of chemical modifications in influencing ASO pharmacology and pharmacokinetic properties in animal

Diagnostic examination of the child with urolithiasis or nephrocalcinosis

Urolithiasis and nephrocalcinosis are more frequent in children then currently anticipated, but still remain under- or misdiagnosed in a significant proportion of patients, since symptoms and signs may be subtle or misleading. All children with colicky abdominal pain or macroscopic hematuria should be examined thoroughly for urolithiasis. Also, other, more general, abdominal manifestations can be the first symptoms of renal stones. The patients and their family histories, as well as physical examination, are important initial steps for diagnostic evaluation. Thereafter, diagnostic imaging should be aimed at the location of calculi but also at identification of urinary tract anomalies or acute obstruction due to stone disease. This can often be accomplished by ultrasound examination alone, but sometimes radiological methods such as plain abdominal films or more sensitive non-enhanced computed tomography are necessary. Since metabolic causes are frequent in children, diagnostic evaluation should be meticulous so that metabolic disorders that cause recurrent urolithiasis or even renal failure, such as the primary hyperoxalurias and others, can be ruled out. The stone is not the disease itself; it is only one serious sign! Therefore, thorough and early diagnostic examination is mandatory for every infant and child with the first stone event, or with nephrocalcinosis

MACI - a new era?

Full thickness articular cartilage defects have limited regenerative potential and are a significant source of pain and loss of knee function. Numerous treatment options exist, each with their own advantages and drawbacks. The goal of this review is to provide an overview of the problem of cartilage injury, a brief description of current treatment options and outcomes, and a discussion of the current principles and technique of Matrix-induced Autologous Chondrocyte Implantation (MACI). While early results of MACI have been promising, there is currently insufficient comparative and long-term outcome data to demonstrate superiority of this technique over other methods for cartilage repair

Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance

20 Jahre pädiatrischer Einsatz in Armenien

20 Jahre sind seit dem grossen Erdbeben vom 7. Dezember 1988 in Armenien vergangen; seither hat sich die Welt erheblich verändert. Vieles wurde damals versprochen, weniges gehalten. Hier ein positives Beispiel und einige Gedanken zur Entwicklungszusammenarbeit