Urinary hydroxypyridinium cross-links of collagen in primary hyperparathyroidism.

Urinary concentrations of the collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were determined in 87 patients with untreated or surgically treated primary hyperparathyroidism (PHPT). Eighty-four healthy individuals, matched for age and sex, constituted the control group for the excretion of pyridinium cross-links. In addition, a subgroup of 25 patients with PHPT was followed longitudinally for up to 2 yr after successful parathyroidectomy. Mean urinary excretion of PYD (46.8 +/- 2.7 nmol/mmol creatinine) and DPD (17.6 +/- 1.3 nmol/mmol creatinine) was significantly higher in patients with untreated PHPT than in normal subjects (P less than 0.001). In the group undergoing successful parathyroidectomy, mean urinary concentrations of PYD (34 +/- 2.5) and DPD (9.4 +/- 0.8) were similar to those in normal controls and significantly lower than those in the untreated patient population (P less than 0.001). The urinary concentration of both cross-links was significantly correlated with serum levels of both alkaline phosphatase and PTH. Mean urinary concentrations of both cross-link compounds decreased significantly within 6 months in patients followed longitudinally and as early as 2 weeks after surgery in individual patients compared to presurgical baseline values. These changes preceded the reduction in serum alkaline phosphatase and hydroxyproline by approximately 6 months. The results demonstrate that urinary hydroxypyridinium cross-links of collagen are useful indices in the clinical assessment of bone involvement in PHPT.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Treatment of ABO Hemolytic Disease with Synthetic Blood Group Trisaccharides

Thirteen infants, 10 with A-O and 3 with B-O hemolytic disease of the newborn (ABO-HDN), were treated with synthetic A or B blood group trisaccharides (ATS, BTS) which cause dissociation of maternal antibody bound to infant red cells. The clinical outcome was compared with that of a control group of 21 infants treated with phototherapy during the preceding year. Exchange transfusion was required in 2 out of 13 infants in the experimental group and in 7 in the control group. A randomized prospective controlled study is necessary to confirm these results.     

Clinical and radiological diagnosis of Crohn's disease in children

Diagnosis of Crohn's disease in children may be delayed because of obscure presentation and inappropriate investigation. The clinical and radiological features in 35 children with Crohn's disease were reviewed retrospectively. The distal ileum and proximal colon were the most common sites of disease. Intestinal symptoms and signs were often overshadowed by nonspecific complaints. Proximal small bowel disease was characterised by oedema, clubbing, anaemia, and stunting of growth. The delay in diagnosis was less than in other series, although most prolonged in the group with proximal disease. We have identified a group of clinical features that strongly suggests Crohn's disease. In these patients, we believe a small bowel enema is justified. Small bowel enema, although invasive, is more effective than barium meal and follow-through for demonstrating Crohn's disease. Severity of radiological changes did not correlate with clinical assessment. Neither bowel stricture nor fistula was found. Radiology of the colon was insensitive and colonoscopy is better for assessing colonic disease.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.