The insulin-like growth factor I generation test in the investigation of short stature

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 ± 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 ± 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.     

Placental weight, birth measurements, and blood pressure at age 8 years

OBJECTIVE: To examine relationships between blood pressure during childhood and both placental weight and body size at birth, in an Australian population. DESIGN: A follow up study of a birth cohort, undertaken when cohort members were aged 8 years. SETTING: Adelaide, South Australia. SUBJECTS: 830 children born in the Queen Victoria Hospital in Adelaide, South Australia, during 1975-6. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure measured when the children were aged 8 years. RESULTS: Blood pressure at 8 years was positively related to placental weight and inversely related to birth weight, after adjusting for the child's current weight. For diastolic pressure there was a decrease of 1.0 mm Hg for each 1 kg increase in birth weight (95% confidence interval (CI) = -0.4 to 2.4) and an increase of 0.7 mm Hg for each 100 g increase in placental weight (95% CI = 0.1 to 1.3). Diastolic pressure was also inversely related to chest circumference at birth, independently of placental weight, with a decrease of 0.3 mm Hg for each 1 cm increase in chest circumference (95% CI = 0.2 to 0.5). CONCLUSIONS: These findings are further evidence that birth characteristics, indicative of fetal growth patterns, are related to blood pressure in later life.     

EICOSAPENTAENOIC ACID IN TREATMENT-RESISTANT DEPRESSION ASSOCIATED WITH SYMPTOM REMISSION,STRUCTURAL BRAIN CHANGES AND REDUCED NEURONAL PHOSPHOLIPID TURNOVER

The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.     

Radiographic changes of the jaws in HbSS and HbSC genotypes of sickle cell disease

This study used panoramic radiographs to evaluate the presence of radiographic changes in the jaws of a population who had sickle cell disease (SCD). The authors compared the frequency of findings between subjects with and without SCD. Panoramic radiographs of 71 subjects with SCD (36 with HbSS and 35 with HbSC) and 52 healthy controls (HbAA) were evaluated for the presence of the following radiographic alterations: radiopaque areas, increased spacing of bony trabeculae, horizontal arrangement of bony trabeculae, and absence of mandibular canal corticalization. The control group had a significantly smaller number of all the radiographic features evaluated. Differences were not statistically significant between the groups with HbSS and HbSC, except for more trabecular spacing in the molar region in the HbSS genotype, suggesting a possible correlation between radiographic findings and disease presentation.     

Epitope specificities and quantitative and serologic aspects of monoclonal complement (C3c and C3d) antibodies

Twenty-two monoclonal antibodies to human C3c and ten to C3d were obtained by hybridization after the immunization of mice with complement-coated human red cells and/or purified human complement components. C3c antibodies were variable in their agglutination reactions with cells coated with C3 by antibody in vitro; more consistent and potent reactions with these cells were observed with anti-C3d, and all anti-C3d reacted with red cells coated with C3 in vivo. Immunoradiometric assays were used to estimate antibody concentration, affinity, and epitope specificity. The antibody content in ascitic fluids varied from less than 0.1 mg per ml to 5.6 mg per ml. The estimated values of antibody affinities for Sepharose-coupled C3 ranged from 2.8 X 10(6) l per M to 5.0 X 10(8) l per M; on average, IgM antibodies had higher affinities than IgG antibodies. Competitive binding assays showed that the monoclonal antibodies recognized at least seven different epitopes, four on the C3c and three on the C3d fragment of C3. When the results of serologic and quantitative assays were compared, no convincing relationship was found between serologic performance and epitope specificity, antibody concentration, or affinity. IgM antibodies generally gave higher agglutination scores than IgG antibodies, and Ig class was the only useful predictor of serologic efficacy.     

Surgery is more cost-effective than splinting for carpal tunnel syndrome in the Netherlands: results of an economic evaluation alongside a randomized controlled trial

Background  

Carpal tunnel syndrome (CTS) is a common disorder, often treated with surgery or wrist splinting. The objective of this economic evaluation alongside a randomized trial was to evaluate the cost-effectiveness of splinting and surgery for patients with CTS.     

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

Background  

The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow.     

Effects of smoking and aging on oxidative DNA damage of human lymphocytes

The effects of H2O2-induced oxidative DNA damage in 80 healthy individuals with relation to age (20-25 and 55-60 years old) and smoking has been investigated with the comet assay technique. Both factors have shown a significant effect upon basal DNA damage with smoking appearing to have the most impact. A differentiation of the four groups response to induced oxidative damage was also observed. A distinctly separate behavior of the younger non-smokers group, when compared with the rest of the categories, was found. This is attributed to the lower degree of initial basal damage that occurs in their lymphocytes.      

Severe microcephaly with normal intellectual development: the Nijmegen breakage syndrome

A brother and sister are described with severe microcephaly of prenatal onset, normal intellectual and motor development, chromosomal breakage and cellular immunodeficiency, which is characteristic of the autosomal recessive condition, Nijmegen breakage syndrome. The proband was a girl who presented at 15 months, with normal developmental milestones and an extremely small head circumference of 36 cm. Twenty per cent of her lymphocytes showed spontaneous translocations involving chromosome 7p13, 7q35, 14q11, and 14q32. The lymphocytes also showed excessive x ray induced chromosome damage. She had T cell lymphopenia, but normal immunoglobulins, and a normal alpha fetoprotein. A brother was born shortly after her diagnosis was made. He also had extreme microcephaly of 28 cm, with similar spontaneous and x ray induced chromosomal breakage, and T cell lymphopenia. Neither child has clinical evidence of immunodeficiency. To test the hypothesis that Nijmegen breakage syndrome and ataxia telangiectasia are allelic disorders, haplotype analysis was carried out in the family using DNA markers spanning the AT locus on chromosome 11q22. The affected boy had a different haplotype from his affected sister. Thus in this family, the Nijmegen breakage syndrome is not allelic to the ataxia telangiectasia locus on chromosome 11q, and the two conditions are genetically distinct. The normal intellect in these children raises questions about normal brain development in the presence of severe microcephaly.     

A prospective 10 year follow up study of patients with neurofibromatosis type 1

OBJECTIVE: To establish the prevalence and incidence of symptoms and complications in children with neurofibromatosis type 1 (NF1) and to assess possible risk factors for the development of complications. DESIGN: A 10 year prospective multidisciplinary follow up study. PATIENTS: One hundred and fifty children diagnosed with NF1 according to criteria set by the National Institutes of Health. RESULTS: In 62 of 150 children (41.3%) complications were present, including 42 (28.0%) children with one complication, 18 (12.0%) with two complications, and two (1.3%) with three complications (mean (SD) duration of follow up 4.9 (3.8) years). Ninety five of the 150 children presented without complications (follow up, 340.8 person-years). The incidence of complications was 2.4/100 person-years in this group. An association was found between behavioural problems and the presence of complications. CONCLUSION: This is the largest single centre case series of NF1 affected children followed until 18 years of age. Children with NF1, including those initially presenting without complications, should have regular clinical examinations.