Muscle fiber dysfunction contributes to weakness in inclusion body myositis

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM.     

The birth rate of hypospadias in the Turku area in Finland

Reports based on national registers of congenital malformations have suggested that the birth rate of hypospadias has increased during the last few decades. Register-based information may, however, have pitfalls because of changes in diagnostics, reporting accuracy and registration system. The aim of this study was to determine the current birth rate of hypospadias in Turku University Central Hospital (TUCH) in Finland. This was a prospective study on live-born boys born in TUCH from 1997 to 1999. In the total birth cohort (n=5,798) as well as in a special subcohort group (n=1,505) 0.3% of boys had hypospadias. Only one scrotal hypospadias was found in a boy who had a chromosomal anomaly. Other hypospadias were glandular or coronal. No increase was found in the birth rate of hypospadias when comparing our result with register-based data of boys born in Finland during the years 1970 to 1986 and surgically treated for hypospadias by the age of 8 years. No difference was found either from malformation register-based data concerning the nationwide birth rate of hypospadias during the years 1993 to 1998. Due to differences in national registration systems between countries, prospective studies with equal assessment criteria are needed in order to make reliable international comparisons.     

Methyl-methacrylate as an embedding medium in histopathology

Methyl-methacrylate embedding makes it possible to obtain semi-thin sections rich in detail and without tissue shrinkage. The procedure requires considerable time and labour, and great care must be taken to prevent heat damage to the tissue during the exothermic polymerization process. The original method given by Burkhardt (1966) and later modifications are described and discussed, with special attention to the practical problems encountered and their solutions.     

Sacral insufficiency fractures: an unsuspected cause of low back pain [clinical conference]

We describe 10 cases of sacral fractures diagnosed within the rheumatology department at Southend Hospital over the last 5 yr. All presented with sudden-onset low back pain. The majority were elderly, frail, with chronic inflammatory disease (six with rheumatoid arthritis, one with polymyalgia rheumatica, one with vasculitis) and had received steroids. Diagnosis was delayed by the inability of plain radiographs to show these fractures and was ultimately demonstrated by technetium scintigraphy/computed tomography scan. We feel that this diagnosis should be considered in elderly patients with rheumatoid arthritis or other risk factors for osteoporosis who present with low back pain and sacral tenderness. Further clues may be parasymphyseal tenderness (suggesting associated pubic ramus fracture), elevated alkaline phosphatase and plain radiograph showing pubic ramus fractures or parasymphyseal sclerosis. Patients with this complication generally have a poor prognosis and two of our patients have died. Seven required in-patient stay (mean 20 days; range 14-41). The mortality, morbidity and costs incurred in management may be comparable to those of femoral neck fractures.      

Prenatal testosterone and luteinizing hormone levels in male rats exposed during pregnancy to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol

Changes in the perinatal testosterone surge have been related to demasculinization of the central nervous system and androgen-dependent growth of the reproductive organs in male mammals. Earlier reports suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with androgen production, but the perinatal effects have remained elusive. In the present study we explored in utero-effects of TCDD (0.05, 0.1, 0.5, and 1.0 microg/kg), introduced on day 13.5 of pregnancy, on prenatal (day 19.5 post-conception [p.c.]) testosterone (T) surge and pituitary luteinizing hormone (LH) production in TCDD-resistant Han/Wistar (H/W) and TCDD-sensitive Long-Evans (L-E) rats. To elucidate estrogenic effects on T and LH production, Sprague-Dawley (S-D) fetuses with previously known DES-sensitivity were exposed in utero to diethylstilbestrol (DES, 100-300 microg/kg) on days 13.5, 15.5, and 17.5 p.c. For comparison, H/W fetuses that responded to TCDD treatments were exposed to DES at concentration of 100 microg/kg. It was found that TCDD has a stimulatory effect on testicular T synthesis in the H/W fetuses and that their circulating T concentrations increased significantly. The effect was not seen in the inbred L-E fetuses, which throughout the study showed considerably low testicular T levels. Pituitary LH concentrations also increased in the H/W fetuses exposed to TCDD. Effects of TCDD (1.0 microg/kg) in the H/W fetuses could be confirmed in vitro by human chorionic gonadotropin (hCG) stimulation assay showing the highest response rate in the TCDD exposed testes. Stimulation of cyclic AMP (adenosine-3', 5'-cyclic monophosphate[cAMP]) production was not considerably altered by in utero TCDD exposure. A significant depression in testicular and plasma T content was seen in the DES-exposed S-D and H/W fetuses, but pituitary LH levels did not alter considerably. In the presence of hCG, DES-exposed testes showed lower in vitro T and cAMP production rates compared to the untreated testes. TCDD (1.0 microg/kg) increased and DES decreased the male body weight gain, but the changes were not sex-dependent. It is concluded that TCDD may increase the amplitude of the prenatal testosterone surge in male rats by stimulating pituitary LH production and enhancing the sensitivity of the fetal testis to LH. DES, on the contrary, apparently impairs testicular steroidogenesis and pituitary function.     

Visuospatial impairment in children and adolescents after liver transplantation

A minority of children with liver transplants exhibit significant delay in global intelligence; others have specific learning disabilities. More specific data on neurocognitive strengths and weaknesses are lacking. Eighteen children aged 7-16 yr, who had undergone LTx in Finland participated in the study. They were assessed on an average 7.6 (s.d. 4.5, range 1.0-15.0) years post-operatively at a mean age of 11.8 (s.d. 3.1, range 7.2-16.1). A standardized test of intelligence (WISC-III), a neuropsychological test battery (NEPSY-II), and a parental questionnaire on the child's development (FTF) were administered. The neuropsychological test profile of the LTx group was compared with that of a matched control group of healthy children. The LTx children achieved on an average normal FSIQ 94.0 and VIQ 99.6. Their Performance Intelligence Quotient (PIQ 88.9, p=0.043) was, however, significantly lower than the population mean. On neuropsychological assessment, the LTx children scored generally lower than the control group (p=0.004), a difference significant in sub-tests assessing visuospatial and visuoconstructive functions and social perception. No differences emerged in sub-tests of attention and executive functions, memory and learning, or language functions. LTx children are at increased risk for impairment in the visuospatial domain.     

6-[18F]Fluoro-l-DOPA Uptake in the Rat Pancreas is Dependent on the Tracer Metabolism

Purpose

6-[¹⁸F]fluoro-l-3,4-dihydroxyphenyl alanine ([¹⁸F]FDOPA) positron emission tomography (PET) is a diagnostic tool which can detect malignancies of the pancreas. We aimed to study whether the manipulation of the [¹⁸F]FDOPA metabolic pathway would change the ¹⁸F-behavior to provide a biochemical foundation for PET imaging of rat pancreas with [¹⁸F]FDOPA.

Procedures

Inhibitors of aromatic amino acid decarboxylase, catechol-O-methyltransferase, monoamine oxidases A and B, or their combinations on [¹⁸F]FDOPA uptake, metabolism, and the regional distribution in the rat pancreas was evaluated using in vivo PET/computed tomography imaging, chromatographic metabolite analyses, and autoradiography.

Results

Enzyme inhibition generally increased the uptake of [¹⁸F]FDOPA derived ¹⁸F-radioactivity in rat pancreas. Dependent on which enzymatic pathway is blocked (or a combination of pathways), different radiolabeled metabolites in pancreas are responsible for this increase in uptake.

Conclusions

Altering the metabolism of [¹⁸F]FDOPA by using various enzymatic inhibitors increased the radioactivity uptake and changed the radiometabolic profile in the pancreas allowing better discrimination between pancreas and surrounding tissues of rat. However, these manipulations did not separate islets from the exocrine pancreas. Elucidating the metabolic behavior of [¹⁸F]FDOPA provides a biochemical foundation of PET imaging of the rat pancreas.     

Have there been changes in children's psychiatric symptoms and mental health service use? A 10-year comparison from Finland

OBJECTIVE: To study the differences in children's psychiatric symptoms and child mental health service use at two time points: 1989 and 1999. METHOD: Two cross-sectional representative samples of 8- to 9-year-old children from southern Finland were compared. The 1989 sample consisted of 985 children, of whom 95% participated, and the 1999 sample consisted of 962 children, of whom 86% participated. Information was gathered from parents and teachers using Rutter's questionnaires and other related determinants of service use and from children using the Child Depression Inventory. The sampling, procedure, and methods were similar at both time points. RESULTS: The overall rate of children's problems assessed by parents and teachers had not increased during the period 1989 to 1999. Boys had fewer psychiatric symptoms in 1999 than in 1989, whereas no clear change had occurred in girls' symptoms, except that, according to parents, girls in 1999 had more hyperactive symptoms. However, children themselves reported more depressive symptoms in the 1999 than in the 1989 sample. In 1989, 2.3% and in 1999, 5.3% of children had used child mental health services. The increase in service use among girls was fourfold. Parental evaluations of child psychopathology and teacher evaluations whether the child was psychologically healthy were the strongest determinants for referral at both time points. Parents preferred to seek help for their children's problems from teachers, school nurses, and school psychologists rather than from specialized child psychiatric services. CONCLUSIONS: There has been an increase in mental health service use especially among girls as well as a convergence of symptom levels by gender. It is important to develop child psychiatric services that are as close to the child's living environment as possible to further reduce the threshold for seeking help and to promote early detection and intervention.