Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke

The contribution of the complement system to cerebral ischemic and ischemia/reperfusion injury was examined in a rabbit model of thromboembolic stroke by delivery of an autologous clot embolus to the intracranial circulation via the internal carotid artery. A two-by-two factorial design was employed to study the impact of complement depletion via pretreatment with cobra venom factor (CVF, 100 U/kg i.v.) in the setting of permanent (without tissue plasminogen activator; t-PA) and transient (with t-PA) cerebral ischemia. Thirty-two New Zealand white rabbits were assigned to one of four groups (n=8, each group): control without t-PA, control with t-PA, CVF without t-PA and CVF with t-PA. In the complement intact animals, t-PA administration resulted in an approximate 30% reduction in infarct size when compared to the group not receiving t-PA (20.4+/-6.6% of hemisphere area vs. 30.1+/-7.2%; mean+/-SEM). However, infarct sizes in the complement depleted rabbits, with (30.7+/-8.2%) or without (30.2+/-7.9%) t-PA, were no different from the control group receiving no therapy. Similarly, no difference in regional cerebral blood flow or final intracranial pressure values was noted between any of the four groups. Complement activation does not appear to be a primary contributor to brain injury in acute thromboembolic stroke.     

Plasma folate levels in preterm infants,with and without a 1 mg daily folate supplement

One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 g/l to a median of 12 g/l, by the 2nd–3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 g/l and a maximum of 1000 g/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05–0.2 mg folate may be preferable for well preterm infants.     

Limiting applications of cryotherapy for severe retinopathy of prematurity.

In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.     

Nutrient intake, adiposity, and diabetes.

To study the role of nutritional factors in the genesis of diabetes, estimations of blood sugar concentration, food intake, and adiposity (as body mass index; BMI) were carried out on three normal population samples--namely, 961 employees of Beecham Ltd, 1005 employees of the Greater London Council, and 1488 middle-aged male civil servants (Whitehall study). Blood sugar concentrations and indices of glucose tolerance correlated positively with the degree of adiposity but tended to be negatively correlated with total food energy intake and its component nutrients (total carbohydrate, sucrose, and fat). This inverse trend was largely accounted for by highly significant inverse correlations between food energy intake and adiposity, a relation found in both sexes and in all three population samples and which extended across the whole range of nutrient intake and BMI. These findings suggest that greater degrees of adiposity are associated with lower than average food energy intakes and hence lower total energy expenditures. The association of increased adiposity with low food energy consumption may indicate an underlying "low energy throughput" state, and it may be the mechanisms of this, as well as the obesity, that are responsible for disease.     

Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein. DNA-PKcs is involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here we compared the toxic effects of benzene on mice (C57BL/6 and 129/Sv) homozygous for the wild-type Prkdc allele and mice (129/SvJ) homozygous for a Prkdc functional polymorphism that leads to diminished DNA-PK activity and enhanced apoptosis in response to radiation-induced damage. Male and female mice were exposed to 0, 10, 50, or 100 ppm benzene for 6 h/d, 5 d/week for 2 weeks. Male mice were more susceptible to benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female mice. We observed similar, large increases in both micronucleated erythrocyte populations in all male mice. Female mice had smaller but significant increases in micronucleated cells. The p53-dependent response was induced in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNA-PK, in restoring genomic integrity following benzene-induced DSB remains equivocal.     

Intradiploic hematoma after skull fracture: case report and literature review

BACKGROUND: Intradiploic hematoma of the skull was first reported in 1934. The pathogenesis of this lesion is unclear. It is a very rare benign reactive process occurring after minor head trauma, with only seven cases reported in the literature to date. CASE DESCRIPTION: A 3-year-old right hand dominant male presented with a non-tender parietal scalp swelling of a 1-year duration. History included a skull fracture located in the same region 24 months before presentation. Neurological examination was unremarkable. Pathological examination after curettage of the lesion revealed features consistent with organizing hematoma. CONCLUSIONS: The pathology of chronic diploic hematoma mimics aneurysmal bone cyst, giant cell tumor, giant cell reparative granuloma, fibrous dysplasia, eosinophilic granuloma, intradiploic epidermoid and dermoid cyst, cavernous hemangioma, circumscribed osteomyelitis, and tuberculous granuloma. Chronic diploic hematoma is a lesion that must be differentiated from various skull lesions both radiologically and histologically as it is amenable to treatment with a complete cure once excised.     

Transjugular liver biopsy effecting changes in clinical management

Although transjugular liver biopsies are frequently performed in patients with impaired blood coagulation, their impact on effecting changes in clinical management has not been assessed. We reviewed our experience with 43 consecutive transjugular liver biopsies performed over 3 years (1998?2000) at Westmead Hospital, Sydney, Australia. The technical success, procedural complication rates and subsequent management of these patients were ascertained from the medical case records. Forty‐two (28 men) patients were studied. The indications for liver biopsy were as follows: assessment of hepatitis/cirrhosis status (n = 21), evaluation of liver dysfunction following bone marrow transplantation (n = 19) and miscellaneous (n = 2). All liver biopsies were performed with a Cook 20‐G transjugular cutting needle device. Adequate histological samples were obtained in 42 (98%) of the 43 biopsies performed. The pre‐biopsy diagnoses were confirmed by histology in 28 cases (65%). A change in clinical diagnosis was observed in 12 (28%) patients, and there were changes to subsequent management in all 12 patients. Four patients developed procedural complications, including small neck haematomas in two patients and a self‐limiting biliary fistula in one. The only major complication was an extracapsular bleed from a hepatic laceration. This patient required emergency surgery but recovered. Transjugular liver biopsies can be effectively and safely performed in high‐risk patients with impaired coagulation. They aid accurate histological appraisal of liver dysfunction in these patients and influence clinical decision‐making.     

beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors

The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.