Diaphragm structure and function in health and disease

The diaphragm is the primary muscle of inspiration, and as such uncompromised function is essential to support the ventilatory and gas exchange demands associated with physical activity. The normal healthy diaphragm may fatigue during intense exercise, and diaphragm function is compromised with aging and obesity. However, more insidiously, respiratory diseases such as emphysema mechanically disadvantage the diaphragm, sometimes leading to muscle failure and death. Based on metabolic considerations, recent evidence suggests that specific regions of the diaphragm may be or may become more susceptible to failure than others. This paper reviews the regional differences in mechanical and metabolic activity within the diaphragm and how such heterogeneities might influence diaphragm function in health and disease. Our objective is to address five principal areas: 1) Regional diaphragm structure and mechanics (GAF). 2) Regional differences in blood flow within the diaphragm (WLS). 3) Structural and functional interrelationships within the diaphragm microcirculation (DCP). 4) Nitric oxide and its vasoactive and contractile influences within the diaphragm (MBR). 5) Metabolic and contractile protein plasticity in the diaphragm (SKP). These topics have been incorporated into three discrete sections: Functional Anatomy and Morphology, Physiology, and Plasticity in Health and Disease. Where pertinent, limitations in our understanding of diaphragm function are addressed along with potential avenues for future research.     

Reliability, performance characteristics, construct validity, and an initial clinical application of a visual object learning test (VOLT)

Whereas verbal learning has received considerable attention by cognitive neuropsychology, spatial object learning has been more resistant to study. The paucity of visual learning data has hampered attempts to clarify if visual learning has unique features with specialized neural substrates. In schizophrenia, severe verbal learning impairment has been established, but lack of comparable visual learning measures has thwarted the dissociation of verbal and visual abilities. The Visual Object Learning Test (VOLT) was developed to examine aspects of visual-spatial learning and memory in a manner analogous to available verbal tests. Studies were performed to establish normative performance characteristics, convergent and divergent validity, and the sensitivity of the VOLT to detection of individual differences in normal (through sex and age) and pathologic variability (through persons with schizophrenia). The results indicated excellent internal consistency, convergent and divergent validity, and sensitivity to the effects of aging and pathology. Persons with schizophrenia were impaired in both learning and retention. The authors conclude that memory impairment in schizophrenia may not be specific to verbal learning.     

Chlamydial serologic studies and recurrent spontaneous abortion

OBJECTIVE: Our purpose was to investigate the putative association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions. STUDY DESIGN: Sera from 106 idiopathic recurrent aborters and 81 of their partners were tested for immunoglobulin G antichlamydial antibodies by whole inclusion immunofluorescence and compared with 3890 sera from a general antenatal population. Positive sera were further investigated by microimmunofluorescence to determine species (Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci) specificity. RESULTS: Twenty-six (24.5%) of women with recurrent spontaneous abortions had immunoglobulin G antichlamydial antibodies compared with 28 (34.6%) of their partners (chi 2 2.25, p < 0.05) and 788 (20.3%) of the general antenatal population (chi 2 1.16, p < 0.05), and the incidence of antibody positivity showed no trend with increasing number of previous abortions. Fourteen women with recurrent spontaneous abortions had antibodies to Chlamydia trachomatis, 12 to Chlamydia pneumoniae. The prevalence of antibodies to C. trachomatis did not differ significantly between women with recurrent spontaneous abortions and their partners, but the male partners had a significantly (p = 0.005) higher prevalence of Chlamydia pneumoniae antibodies. Chlamydial antibody seropositivity did not correlate with subfertility or subsequent pregnancy outcome. CONCLUSION: There is no association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortion.     

Immunochemical analysis of dopamine transporter protein in Parkinson's disease

The plasma membrane dopamine transporter (DAT) is considered to be a reliable marker of presynaptic dopaminergic terminal loss. Previous in vivo imaging and postmortem binding studies have detected a loss in striatal DAT binding in Parkinson's diseased (PD) brain; however, these techniques have poor spatial resolution and may suffer from nonspecific binding of some ligands. In this study, we use novel highly specific monoclonal antibodies to distinct epitopes of human DAT to quantify and localize the protein. Western blot analysis revealed marked reductions in DAT immunoreactivity in putamen, caudate, and nucleus accumbens of PD brain compared with control cases, and the reductions were significantly correlated to disease duration. Immunohistochemistry revealed DAT-immunoreactive fibers and puncta that were dense throughout the striatum of control brains but that were drastically reduced in putamen of PD brains. Caudate from PD brains showed a significant degree of sparing along the border of the ventricle, and the nucleus accumbens was relatively preserved. An unexpected finding was that discrete islands of DAT immunoreactivity were preserved within the matrix of PD putamen. Thus, immunological analysis of DAT protein provides novel and sensitive means for localizing and quantifying DAT protein in PD and other neurological disorders involving dopaminergic systems.     

Unrelated donor bone marrow transplantation for Fanconi anemia

This paper describes the approach taken at the University of Queensland to broaden the scope of curriculum design to involve rural general practitioners, medical students and rural health care consumers. A form of nominal group process in serial telephone teleconferences was used, with a group of rural general practitioners, to develop and pilot curriculum content, learning strategies and assessment methods. Medical students assisted in the evaluation of the curriculum and representatives of rural organisations were consulted about the value of hosting medical students in rural communities. The three groups made significant contributions to the project. The results will be trialed for the entire year 6 cohort (240 students) in 1995 and will form the basis of the planned rural practice term in the new graduate course.     

Simultaneous determination ofSonchus arvensis L. triterpenes by gas chromatography-mass spectrometry

Sonchus arvensis L. or sow thistle has proved an excellent source of pentacylic triterpenes; triterpenes account for about 6% of the crude lipid extract or 0.2% of the dried plant. Composition of the triterpenoid fraction, as indicated by gas chromatography of the corresponding acetates, was α-amyrin (9%), β-amyrin (21%), lupeol (13%), taraxasterol (24%) and pseudo-taraxasterol (12%). A single, long-chain alcohol (16%) was also present. The nature of the triterpenoids was defined using gas chromatography and gas chromatography-mass spectrometry (GC/MS) and confirmed by direct comparison with authentic samples. The use of combined GC/MS proved extremely valuable in the simultaneous analysis of a mixture of triterpene acetates and greatly reduced the time needed to phytochemically evaluate these compounds.     

Serine 257 phosphorylation regulates association of polyomavirus middle T antigen with 14-3-3 proteins

Polyomavirus middle T antigen (MT) is phosphorylated on serine residues. Partial proteolytic mapping and Edman degradation identified serine 257 as a major site of phosphorylation. This was confirmed by site-directed mutagenesis. Isoelectric focusing of immunoprecipitated MT from transfected 293T cells showed that phosphorylation on wild-type MT occurred at near molar stoichiometry at S257. MT was previously shown to be associated with 14-3-3 proteins, which have been connected to cell cycle regulation and signaling. The association of 14-3-3 proteins with MT depended on the serine 257 phosphorylation site. This has been demonstrated by comparing wild-type and S257A mutant MTs expressed with transfected 293T cells or with Sf9 cells infected with recombinant baculoviruses. The 257 site is not critical for transformation of fibroblasts in vitro, since S257A and S257C mutant MTs retained the ability to form foci or colonies in agar. The tumor profile of a virus expressing S257C MT showed a striking deficiency in the induction of salivary gland tumors. The basis for this defect is uncertain. However, differences in activity for the wild type and mutant MT lacking the 14-3-3 binding site have been observed in transient reporter assays.     

The source of gallium-67 in gastrointestinal contents: concise communication

The sources of Ga-67 in gastrointestinal (GI) contents, and factors affecting its secretion were studied in rats. To prevent loss of fecal Ga-67, the anus was sutured before intravenous injection of Ga-67 citrate. Secretion of Ga-67 into the contents of the GI tract was rapid, 3, 6, and 9% of the injected dose were secreted at 1, 6, and 24 hr after injection, respectively. In contrast, Ga-67 concentration in the GI tissues remained relatively constant throughout this period. Analysis of Ga-67 contents of various parts of the GI trace revealed that small intestine is its major source, contributing 60% while the bile contributes 20%, large intestine 10%, GI contents. In contrast, the serum unbound iron-binding capacity (UIBC) played an important role in the Gl secretion of Ga-67 reducing the serum UIBC reduced the Ga-67 secretion into GI contents.     

Constipation in the elderly

Constipation affects as many as 26 percent of elderly men and 34 percent of elderly women and is a problem that has been related to diminished perception of quality of life. Constipation may be the sign of a serious problem such as a mass lesion, the manifestation of a systemic disorder such as hypothyroidism or a side effect of medications such as narcotic analgesics. The patient with constipation should be questioned about fluid and food intake, medications, supplements and homeopathic remedies. The physical examination may reveal local masses or thrombosed hemorrhoids, which may be contributing to the constipation. Visual inspection of the colon is useful when no obvious cause of constipation can be determined. Treatment should address the underlying abnormality. The chronic use of certain treatments, such as laxatives, should be avoided. First-line therapy should include bowel retraining, increased dietary fiber and fluid intake, and exercise when possible. Laxatives, stool softeners and nonabsorbable solutions may be needed in some patients with chronic constipation.