The cytotoxicity of DNA carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells.

Carboxymethylating agents are potential sources of endogenous DNA damage that have been proposed as possible contributors to gastrointestinal carcinogenesis. The cytotoxicity of the model DNA carboxymethylating agent azaserine was investigated in human cells. Expression of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) did not affect sensitivity to the drug in two related Raji Burkitt's lymphoma cell lines. DNA mismatch repair-defective variants of Raji cells which display increased tolerance to DNA methylation damage were not selectively resistant to azaserine. Complementary results were obtained with a second carboxymethylating agent, potassium diazoacetate. In contrast, lymphoblastoid cell lines representative of each of the xeroderma pigmentosum complementation groups, including the variant, were all significantly more sensitive to azaserine than nucleotide excision repair-proficient cells. The hypersensitivity of XP cells was not due to systematic differences in the concentrations of intracellular thiol compounds or related thiol metabolizing enzymes. The data indicate that of the two types of potentially lethal DNA damage which azaserine introduces, carboxymethylated bases and O(6)-methylguanine, the former are repaired by nucleotide excision repair and are a more significant contributor to azaserine lethality in human cells.     

Intrahepatic encystment of umbilical vein catheter infusate

Massive hepatomegaly in a 2.1 kg female infant, with an indwelling umbilical vein catheter for total parenteral nutrition, occurred on the 10th day of life. Ultrasound and computed tomography studies revealed a large hepatic cyst filled with the catheter infusate. Percutaneous drainage brought about subsequent recovery. To our knowledge, this complication of umbilical vein catheter use has not been previously reported.     

Examining the sensitivity of an injury surveillance program using population-based estimates.

This study uses population-based estimates to assess the sensitivity and representativeness of an injury surveillance system using a 1-year population-based approach. Data from the Ottawa Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) site (Children's Hospital of Eastern Ontario) were compared with those from six expansion sites. The overall sensitivity of CHIRPP was 43% of all treated injuries and 57% of injuries treated at emergency departments. CHIRPP was less likely to be representative for older children and more likely to capture children with more severe injuries. The limitations related to using CHIRPP for representing population-based injury remain fairly stable over time. A one-time population-based sample can provide useful information to add to routinely collected injury surveillance.     

Association of reduced selenium status in the aetiology of recurrent miscarriage

Objective To determine whether recurrent miscarriage is associated with reduced selenium status.
Design Case–control study.
Setting Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary and Glasgow Royal Maternity Hospital.
Population Twenty nonpregnant women with a history of unexplained recurrent miscarriage, and 47 nonpregnant parous women with a history of at least one successful pregnancy and no more than one miscarriage.
Methods A 7 mL blood sample from each woman was collected into lithium heparin 'vacutainer' tubes. Samples were centrifuged at 3000 g for 15 minutes, and plasma was extracted and stored at −20°C. Selenium concentrations were measured using a fluorescence spectrophotometer. The selenium concentrations in the two groups were compared and the differences examined using the Student's t test.
Main outcome measures Plasma selenium concentration (μg/L).
Results The mean selenium concentration for women with a history of unexplained recurrent miscarriage was 67.7 μg/L (SD 16.4). The selenium level for the women with no history of recurrent miscarriage was 70.3 μg/L (SD 12.7). There was no difference in selenium concentrations between the two groups (   P = 0.53  ).
Conclusions In this study there is no association between unexplained recurrent miscarriage and reduced selenium status, implying that reduced selenium status is not a factor in the pathogenesis of recurrent miscarriage. We can find no rationale for a trial of selenium therapy in women with a history of recurrent miscarriage.     

Aminoaciduria is an earlier index of renal tubular damage than conventional renal disease markers in the gentamicin-rat model of acute renal failure

There are currently no reliable early markers of renal tubular damage. Since aminoaciduria is an accompanying feature of this condition, the usefulness of increased urinary amino acid excretion as a marker was investigated by inducing renal tubular necrosis in male Wistar rats by the administration of gentamicin (40 mg/kg/d) for 14 d. Plasma amino acids, urea, creatinine, protein and electrolytes, and urine amino acids, protein and N-acetylglucosaminidase (a lysosomal enzyme) were measured over a 20 d period. Amino acid excretion increased dramatically within 24 h of the initial dose for 14 of the 16 amino acids measured. The conventional renal disease markers listed above did not increase until after day 7. Glomerular damage caused by puromycin aminonucleoside did not induce aminoaciduria until marked proteinuria occurred (day 9), and even then amino acid excretion was much less than that caused by gentamicin. To distinguish whether the gentamicin-induced aminoaciduria was a consequence of tubular damage or inhibition of amino acid transport, isolated rat kidneys were perfused with a Krebs-Henseleit albumin buffer with and without gentamicin for 20 min, during which time urinary amino acids were quantitated. Gentamicin did not inhibit amino acid reabsorption. Thus, it appears that in the rat-gentamicin model of acute renal failure, urinary amino acids are early markers of renal tubular damage.     

The significance of traumatic haematoma in the region of the basal ganglia.

Computed tomography demonstrated a haematoma in the region of the basal ganglia in 61 of 2000 head injured patients. In 41 the haematoma occurred as an isolated lesion while in 20 there was another associated intracranial haematoma. Clinical and radiological differences within these groups are discussed. The patients with basal ganglia haematoma were more severely injured than those in a group who had an intracranial haematoma evacuated by craniotomy and the findings closely resembled those of a group of patients who had sustained diffuse brain damage. They share many features with those of patients with diffuse white matter injury and have a worse prognosis than other traumatic intracranial haematomas.