Carriers for precipitating nucleic acids

One hundred and forty nine patients underwent thyroid and parathyroid surgery over a nine year period. The most common indications for surgery were the presence of a solitary thyroid nodule (56%) or the onset of pressure symptoms (30%). Carcinoma was found in 7.4% of cases. Wound complications occurred in 5%. The permanent nerve injury rate was 0.67%. The incidence of permanent hypothyroidism after surgery was 4%. No patients developed permanent hypoparathyroidism.     

Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.     

Integrated radiation hybrid and yeast artificial chromosome map of chromosome 9p

OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.     

Delayed traumatic aorto-pulmonary artery fistula

Delayed aorto-pulmonary artery fistula represents an uncommon delayed sequelae of penetrating cardiac trauma. A case is presented that demonstrates the need for a high index of suspicion, follow-up, and a complete evaluation of the patient who survives a penetrating heart injury. The mechanisms of delayed presentation, diagnosis, and management of the fistula are discussed.     

Kinetics of circulating TNF-alpha and TNF soluble receptors following surgery in a clinical model of sepsis

The interrelationship between cytokines and their natural antagonists in patients with systemic sepsis are incompletely understood. We have followed the changes in serum levels of TNF-alpha and the two soluble receptors (TNF-sr) in a clinical model of post-operative sepsis. Serial blood samples were taken in patients undergoing percutaneous nephrolithotomy (PCNL) starting pre-operatively and continuing for 24 h thereafter. The levels of TNF-alpha and TNF-sr were raised in patients who became clinically septic and correlated well with the severity of sepsis (using the APACHE III score). In septic patients there was no difference in the pattern of changes in the two types of receptor (TNF-sr55 and TNF-sr75). However, in non-septic patients TNF-sr75 was higher in those with endotoxaemia than those without. This difference was not observed with TNF-sr55 which suggests a different mechanism of release or degree of sensitivity for the two soluble receptors. Regardless of severity of illness, the levels of all three molecules (TNF-alpha and the two receptors) appeared to start rising at about the same time point. The peak TNF-alpha level was reached earlier (2-4 h) than that of the two TNF-sr (4-8 h). The relative rise in TNF-alpha was greater than that of the soluble receptors and this difference was even more marked in those with more severe sepsis. The relationship between peak TNF-alpha and peak TNF-sr was non-linear and the concentration of each TNF-sr appeared to plateau at the higher levels of TNF-alpha. This suggests the exhaustion of a limited pool or saturation of the rate of release. Taken together, these results suggest sepsis develops because of delayed and insufficient secretion of TNF-sr compared with TNF-alpha.     

Purification and crystallization of complexes modeling the active state of the fragile histidine triad protein

Fragile histidine triad protein (Fhit) is a diadenosine triphosphate (ApppA) hydrolase encoded at the human chromosome 3 fragile site which is frequently disrupted in tumors. Reintroduction of FHIT coding sequences to cancer cell lines with FHIT deletions suppressed the ability of these cell lines to form tumors in nude mice even when the reintroduced FHIT gene had been mutated to allow ApppA binding but not hydrolysis. Because this suggested that the tumor suppressor activity of Fhit protein depends on substrate-dependent signaling rather than ApppA catabolism, we prepared two crystalline forms of Fhit protein that are expected to model its biologically active, substrate-bound state. Wild-type and the His96Asn forms of Fhit were overexpressed in Escherichia coli, purified to homogeneity and crystallized in the presence and absence of ApppA and an ApppA analog. Single crystals obtained by vapor diffusion against ammonium sulfate diffracted X-rays to beyond 2.75 A resolution. High quality native synchrotron X-ray data were collected for an orthorhombic and a hexagonal crystal form.      

S-adenosylmethionine metabolism and DNA methylation in hydrazine-treated rats

The treatment of rats with hepatotoxic doses of hydrazine (NH2-NH2) induces the rapid formation of 7-methylguanine and O6-methylguanine in liver DNA. The methyl moiety in these reactions might be derived from the cellular S-adenosylmethionine pool because radioactivity administered to these rats as methionine rapidly appears in the DNA as methylated guanine. An increased incorporation of radioactivity into 5-methylcytosine was previously reported followed by subsequent suppression. This increased radiolabeling of 5-methylcytosine coincided with time of maximal DNA guanine methylation. To determine the nature of S-adenosylmethionine metabolism during the period of DNA methylation induced by hydrazine treatment, and to determine if the increased radiolabeling of 5-methylcytosine at this time reflected an actual increase in 5-methylcytosine synthesis, liver DNA synthesis and S-adenosylmethionine levels and turnover were assayed. Liver S-adenosylmethionine concentrations varied slightly between control rats and hydrazinetreated rats during the first five hours after hydrazine administration, and no difference was detectable in the incorporation of administered [3H]methionine into S-adenosylmethionine. Because S-adenosylmethionine specific radioactivity in hydrazine-treated rats was not different from control rats, the previously observed increased radiolabeling of 5-methylcytosine appeared to represent an actual increase in synthesis. This conclusion was supported by finding that incorporation of radioactive thymidine into DNA was also accelerated immediately following hydrazine administration, again followed by a decrease. 5-Methylcytosine sythesis, therefore, appears to follow DNA synthesis during hydrazine toxicity, and formation of 7-methylguanine and O6-methylguanine in liver DNA of hydrazine-treated rats occurs during a short period of increased DNA sythesis and 5-methylcytosine formation very early in hydrazine toxicity.