RAMIPRIL REDUCES ALBUMINURIA IN DIABETIC RATS FED A HIGH PROTEIN DIET

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.     

Penetrating sledding injuries to the lower torso -- 2 case reports

Sledding accidents are frequent and vary in severity. Penetrating sledding injuries are uncommon but may be devastating. Snow-racers--sleds with both steering and braking devices--may be associated with an increased rate of injury. The authors present 2 cases of lower-torso penetrating trauma associated with the use of snow-racers. Both cases involved penetration--of the perineum in one case and the inguinal area in the other--by wooden sticks. Both patients recovered fully after prompt surgical intervention. The authors suggest that the absence of a protective panel at the front of the snow-racer may result in the sledder's lower torso being more exposed to objects encountered while sledding. The injuries reported raise concerns about the safety of modern sleds and the possibility that design changes are needed.     

Cloning from the thyroid of a protein related to actin binding protein that is recognized by Graves disease immunoglobulins.

Human actin binding protein (ABP) links specific membrane glycoproteins to cytoskeletal actin microfilaments. In human platelets and leukocytes, ABP directly links, respectively, the membrane glycoproteins GPIb and the high-affinity Fc receptor for IgG (Fc gamma IR) to cytoskeletal actin microfilaments. Similar interaction between the thyrotropin (TSH) receptor and ABP in endocrine cells might explain the rapid and profound disruption of actin microfilaments induced by TSH in cultured thyroid follicular cells. By screening a thyroid lambda gt11 cDNA expression library with serum from a Graves disease patient, we identified a clone encoding a protein, designated truncated ABP (TABP), that shares extensive homology (approximately 70%) with ABP. TABP is a truncated ABP-like protein with an open reading frame of 195 aa that encodes a protein of approximately 21 kDa. TABP lacks an actin binding domain but contains two predicted beta-sheet repeats within which is a putative dimerization domain and between which lies a putative glycoprotein binding site containing a consensus site for phosphorylation by Ca(2+)-calmodulin kinase II. TABP contains a unique C-terminal insertion within which lies a hydrophobic predicted membrane-associated region, absent from ABP. Although TABP mRNA is expressed widely, immunoblot analysis demonstrated the presence of TABP antibodies specifically in the sera of a minority of subjects with autoimmune thyroid disease. A 24-residue sequence of similarity was identified between the TSH receptor and platelet glycoprotein GPIb alpha that may represent a transmembrane ABP binding site. We suggest, therefore, that signal transduction by TSH in the thyroid involves direct linkage of the TSH receptor to actin microfilaments by ABP and that TABP may interact with ABP to mediate TSH-induced actin microfilament disruption.     

Ultrastructural Cytochemistry of Leukaemic Cells: Characterization of the Early Small Granules of Monoblasts

An ultrastructural study of blast cells showing either monocytic or granulocytic differentiation was carried out with the acid phosphatase (AP) and myeloperoxidase (MPO) reactions. Eight cases of acute myeloid leukaemia (AML) and three of chronic granulocytic leukaemia in blast crisis were studied. A hitherto unrecognized small lysosomal granule characterized by AP activity and lack of MPO was present in the majority of cells of all six monoblastic leukaemias. These granules ranged from 0.05 to 0.2 micron in size and were distributed throughout the cytoplasm, frequently at the periphery of the cells. A small proportion of monoblasts showed AP reactivity in the Golgi cisternae. Both AP and MPO were positive in the granules of promonocytes; however, MPO positive granules were predominant in late promonocytes. Larger granules (0.2--0.6 micron) with MPO reactivity were characteristic of myeloblasts. In only two out of four cases did these granules show AP positivity, suggesting that, in contrast to monoblasts, AP activity is a late feature of myeloblastic differentiation. This study shows that ultrastructural cytochemistry may be helpful in the recognition and classification of acute leukaemias by demonstrating the early differentiation features of monocytic and granulocytic precursors.     

Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

BACKGROUND: Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants. METHODS: Perioperatively, 17 neonates and infants < or =160 days of age received one rectal paracetamol dose (mean 23.9 mg/kg (+/-4.2 mg/kg)). Blood samples were drawn at 60, 120, 180, 240, 300 and 360 min, according to the infants' weights. Plasma paracetamol concentrations were measured by a Colorometric Assay, Ectachem Clinical Chemistry Slides (Johnson & Johnson Clinical Diagsnostics). RESULTS: The plasma paracetamol concentrations were mainly below the therapeutic (i.e. antipyretic) range of 66-132 micromol/l and did not exceed 160 micromol/l in any infant. The mean maximum plasma concentration (Cmax) was 72.4 micromol/l (+/-33.5 micromol/l) and the time to Cmax, i.e. the mean Tmax was 102.4 min (_+59.1 min). The mean "apparent" terminal half-life (n=10) was 243.6 min (+/-114.1 min). CONCLUSION: The absorption of rectal paracetamol (mean dose 23.9 mg/kg, +/-4.2mg/kg) in young infants <160 days is variable and often prolonged and achieves mainly subtherapeutic plasma concentrations.     

Managing Meningococcal Disease in the United States: Hospital Case Characteristics and Costs by Age

OBJECTIVE: Meningococcal disease occurs worldwide. Approximately 1400 to 2800 cases are reported in the United States annually. The goal of this analysis was to examine hospitalized cases of meningitis and meningococcemia to identify case characteristics, resource use, and inpatient care costs. METHODS: International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes 036.0-036.9 were used to identify cases from roughly 1000 hospitals in four all payer state discharge databases. Multiyear data (1999-2001) were examined to identify demographics, admission month, health service utilization, and hospital costs by age group: infant (<1 years), children (1-10 years), adolescent (11-17 years), young adult (18-22 years), adults (23-49 years), and adults (> or =50 years). Cost estimates include accommodations, ancillary and physician services, reported in 2003 US dollars. RESULTS: Of 1654 cases of meningococcal disease identified, meningococcemia was coded for 51%. Adults accounted for 33% of the cases. The highest rate of admissions occurred from January through March and 62% were admitted via the Emergency Department. Inpatient case fatality rate was 6.4%; 71% of those who died had meningococcemia. The mean length of stay was 9 days. Of survivors, 91% were discharged home (1% with intravenous medications and 11% with other home health-care services) while 7% required further subacute inpatient care. The average cost per hospitalization was estimated at 23,294 dollars per patient. Infants had the lowest average cost per stay (16,793 dollars) and adolescents had the highest (28,202 dollars). CONCLUSIONS: The presence of meningococcemia results in a greater death rate, longer length of stay, and increased care costs. Meningococcal disease has substantial economic, as well as profound clinical consequences for patients of all ages.     

Use and misuse of cost-effectiveness terminology in the gastroenterology literature: a systematic review

OBJECTIVES: The increased popularity of economic analyses for evaluating medical interventions has given rise to concern about the rigor with which economic constructs and terminology are used. True cost-effectiveness analysis considers both the costs and outcomes of alternative interventions. A systematic review of the gastroenterology literature was undertaken to evaluate how appropriately cost-effectiveness is assessed. METHODS: A structured MEDLINE search identified all studies published in major gastroenterology journals between 1980 and 1998 that claimed in their abstracts to have assessed the cost-effectiveness of an intervention. Blinded copies of eligible studies were assessed by two independent reviewers who used standard criteria to evaluate the use of economic terminology and key economic constructs. Discrepancies were resolved by consensus. Studies met a "broad criterion" for appropriateness by evaluating both costs and effects and a "strict criterion" by demonstrating dominance of one strategy or considering both incremental costs and incremental effects. RESULTS: Of 110 eligible studies, 77 (70.0%) met the broad criterion and 62 (56.4%) met the strict criterion for appropriateness. This did not seem to vary with either journal impact factor or publication year. Only eight of 18 studies reporting an incremental cost-effectiveness ratio compared its value to an external standard. Few studies explicitly stated their analytic perspective, and a minority of those with time horizons longer than 1 yr had discounted future costs or effects. CONCLUSIONS: Although most studies seem to use cost-effectiveness terminology well, there remains room to improve the rigor with which economic terminology and constructs are applied.     

The Washington State Intergenerational Study of Birth Outcomes: methodology and some comparisons of maternal birthweight and infant birthweight and gestation in four ethnic groups

A statewide database of vital records and hospital discharge summaries of obstetric and neonatal admissions for Washington State in 1987-95 was linked to the birth certificates of mothers born in the state. A total of 46,000 births to mothers of four racial/ethnic groups were studied: Whites, African-Americans, Native Americans and Hispanics. For all four groups inverse associations were found between maternal birthweight and infant low birthweight and preterm birth. The birthweight distribution of African-American mothers was displaced markedly downwards compared with the Whites; this difference in maternal birthweight is offered as a partial explanation of the greater prevalence of suboptimal pregnancy outcomes in the former. In contrast, the maternal birthweight distributions of Whites, Native Americans and Hispanics are similar; differences in pregnancy outcomes are probably more related to maternal preconceptional and postnatal factors in these groups as well as differences in pregnancy-related factors. Mothers' birthweight may have clinical value in identifying high-risk pregnancies.     

Ultrasound identification of apparently normal male genitalia in a 46,X,+mar fetus.

A level II ultrasound examination revealed a scrotum and penis in a fetus with a 46,X,+mar chromosome complement. The marker was subsequently considered to be a del(Y)(q11). A phenotypically normal male infant was born. Detailed ultrasound examination of similar cases for visualisation of the genitalia is recommended.