Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle

The purpose of this study was to investigate the effects of supra-physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo-physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross-sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17beta-oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30+/-0.29, 1.16+/-0.38, 1.20+/-0.29 and 1.26+/-0.34 N mm-2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33+/-0.20 N mm-2 at week 12 of pregnancy, 1.51+/-0.42 N mm-2 at week 20, 1.15+/-0.26 N mm-2 at week 36 and 0.94+/-0.31 N mm-2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force-generating capacity of young women.     

IgG subclass distribution and relative functional affinity of anti-myeloperoxidase antibodies in systemic vasculitis at presentation and during follow-up.

Circulating IgG autoantibodies to myeloperoxidase (MPO) are associated with renal vasculitis and have been implicated in its pathogenesis. However, raised levels of these autoantibodies may persist during clinical remission. We tested whether this paradox could be explained by immunoglobulin subclass switching during disease evolution, since different subclasses have different immunological and biochemical properties. Sera with anti-myeloperoxidase (anti-MPO) activity from 33 patients with active disease and 20 anti-MPO positive follow-up sera were studied by an ELISA using a panel of anti-human IgG subclass monoclonal reagents previously calibrated on human myeloma proteins. Anti-MPO subclass distribution in initial sera was: IgG1, 31 (94%); IgG2, 10 (30%); IgG3, 24 (73%); and IgG4, 22 (67%). IgG3 anti-MPO decreased during follow-up (P less than 0.02), with no change in IgG1 and IgG4. Relative functional affinity of anti-MPO antibodies in purified IgG subclasses was studied by the diethylamine method. IgG3 fractions consistently had a greater affinity for MPO than the other subclasses. Sequential studies in four patients demonstrated an affinity maturation for IgG1 and IgG4 anti-MPO as IgG3 anti-MPO disappeared. We conclude that dynamic changes of subclass distribution and affinity may explain discrepancies between anti-MPO antibody titre and disease expression.     

Sequence variation and size ranges of CAG repeats in the Machado-Joseph disease, spinocerebellar ataxia type 1 and androgen receptor genes

A subgroup of trinucleotide repeat diseases result from abnormalexpansions of CAG repeats which are translated into polyglutaminestretches. As yet there is little understanding of how the polyglutaminesfunction either normally, or when expanded. We have investigatedthese sequences in the Machado-Joseph disease, androgen receptorand spinocerebellar ataxia type 1 genes in humans and otherprimates. None of the 748 normal chromosomes that were examinedhad more than 34 uninterrupted gluta-mine codons in the Machado-Josephdisease gene. Similarly, no normal alleles with more than 39uninterrupted glutamine codons have been reported for the otherdisease genes associated with polyglutamine expansions. Sequenceanalyses of the repeats in primates revealed shorter polyglutaminestretches in some of the non-human primates at all three lociand marked diversions from the expected polyglutamines in theorang-utan Machado-Joseph gene and in the marmoset spinocerebellarataxia type 1 gene. These data suggest that conservation ofthese polyglutamine stretches may not always be necessary fornormal gene function.     

Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection

Staphylococcus aureus and Escherichia coli are among the most prevalent species of gram-positive and gram-negative bacteria, respectively, that induce clinical mastitis. The innate immune system comprises the immediate host defense mechanisms to protect against infection and contributes to the initial detection of and proinflammatory response to infectious pathogens. The objective of the present study was to characterize the different innate immune responses to experimental intramammary infection with E. coli and S. aureus during clinical mastitis. The cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), two proteins that contribute to host recognition of bacterial cell wall products, were studied. Intramammary infection with either E. coli or S. aureus elicited systemic changes, including decreased milk output, a febrile response, and induction of the acute-phase synthesis of LBP. Infection with either bacterium resulted in increased levels of interleukin 1beta (IL-1beta), gamma interferon, IL-12, sCD14, and LBP in milk. High levels of the complement cleavage product C5a and the anti-inflammatory cytokine IL-10 were detected at several time points following E. coli infection, whereas S. aureus infection elicited a slight but detectable increase in these mediators at a single time point. Increases in IL-8 and tumor necrosis factor alpha were observed only in quarters infected with E. coli. Together, these data demonstrate the variability of the host innate immune response to E. coli and S. aureus and suggest that the limited cytokine response to S. aureus may contribute to the well-known ability of the bacterium to establish chronic intramammary infection.     

Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1

Indian Journal of Pediatrics - Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at...     

Orthopaedic manifestations of achondroplasia

Achondroplasia is a common cause of short stature. The condition is often encountered on the Trauma and Orthopaedic FRCS examination. This review covers the aetiology, clinical and radiographic features. Current general and orthopaedic treatments are discussed including potential medical developments with natriuretic peptide.     

Tissue necrosis under a Nance palatal arch: a case report

A Nance palatal arch is a method of reinforcing anchorage to help prevent mesial movement of maxillary first permanent molars. It is recognised that it is difficult to maintain oral hygiene around the appliance and that iatrogenic damage can occur. We present a case of a 22-year-old male patient in whom the palatal mucosa became necrotic, palatal bone became exposed and long-term periodontal damage occurred. We describe the case, his treatment and the resolution of the inflammation as well as exploring the causes for the damage and alternate treatment options.