X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features

The radiologic studies of 38 essentially untreated adults with X-linked hypophosphatemia (XLH) were reviewed to determine the prevalence of radiologic features, to compare the findings in men and in women, and to elucidate the natural history of the disease by comparing the findings in young, intermediate-age, and older patients. Bone-reinforcement lines were common, but no characteristic mineral mass alteration was established. Looser zones were more prevalent in older subjects. Osteoarthritis was common, occurring in the ankles, knees, feet, sacroiliac joints, and wrists. Enthesopathy was infrequent in the younger group but was present in every member of the intermediate and older groups and was often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Three new skeletal alterations in XLH were found to be common: flaring of the iliac wings, trapezoidal distal femoral condyles, and alterations in talar morphology, including shortening of the talar neck and flattening of the talar dome. Technetium-99m methylene diphosphonate scintigrams of 17 subjects were often abnormal, depicting bowing deformity and focal tracer accumulation in diaphyseal cortices and in periarticular and extraarticular regions. The mean metabolic index was moderately elevated (4.0). Both radiographic and scintigraphic findings were more severe in men, consistent with hemizygosity. The natural history of untreated XLH in both sexes is characterized by the development of a variety of age-related skeletal abnormalities during adulthood.     

Humoral immunity in allograft rejection. The role of cytotoxic alloantibody in hyperacute rejection and enhancement of rat cardiac allografts

The role of humoral immunity in graft rejection in the rat model remains controversial. Passive transfer of cytotoxic alloantibody (CAA) has resulted either in hyperacute rejection or in graft enhancement. This study examines the effect of transfer of CAA on cardiac allograft survival in three rat strain combinations that are fully mismatched at the major histocompatibility (MHC) loci. Strain-specific immune responsiveness in donor-recipient pairs varied from low (Lewis-to-ACI) to high (ACI-to-Lewis) as measured by mixed lymphocyte reactions. CAA was obtained from rats sensitized by three successive skin grafts at weekly intervals. Group 1 (high responder recipients), which consisted of Lewis rats presensitized to ACI and had a lymphocytotoxicity titer of 1:512 to 1:2048, rejected ACI cardiac allografts in 10.8 +/- 7.2 hr compared with 6.5 +/- 0.5 days in naive controls (p less than 0.001). Injection of 1 ml of high-titer CAA into naive Lewis rats immediately after ACI cardiac grafting led to hyperacute rejection of ACI hears in 2.1 +/- 0.8 hr while 1 ml of CAA followed by 2 ml of guinea pig complement (GPC) resulted in even faster rejection (mean survival time (MST) of 23.8 +/- 4.7 min). Injection of 2 ml GPC alone or in combination with 1 ml naive Lewis serum had no effect on graft survival. Multiple pretransplant injections of 1 ml of CAA on days -3, -2,-1, and 0 relative to transplantation resulted in significant prolongation of allograft survival (MST of 10.3 +/- 0.3 days; P less than 0.01). In group 2 (intermediate responder recipients), where Lewis rats were presensitized to WF strain and where cytotoxicity titer was 1:16 to 1:256, the recipients rejected WF hearts in 23.8 +/- 5.8 hr compared with 6.8 +/- 0.8 days in unsensitized control recipients (P less than 0.001). Injection of 1 ml of Lewis anti-WF CAA resulted in prolonged graft survival of 9.7 +/- 3.5 days, while injection of 1 ml of CAA followed by 2 ml of GPC caused hyperacute rejection in 104 +/- 61.7 min. Pretransplant injections of CAA on days -3, -2, -1, and 0 resulted in enhancement, with an MST of 16.3 +/- 1.3 days (P less than 0.001). In group 3 (low responder recipients), ACI presensitized to Lewis developed a cytotoxicity titer of 1:2 to 1:32 and rejected Lewis hearts in 5.3 +/- 0.4 days compared with 10.6 +/- 1.0 days in naive recipients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Coeliac plexus block and cephalic spread of injectate

Extensive cephalic spread of solution occurred in three out of seven cases studied during coeliac plexus blockade. Spread on to cardiac nerves and plexus may be a factor in hypotension following this procedure. Incremental dosage and careful screening is recommended.     

Pathogenic mitochondrial mt-tRNAAla variants are uniquely associated with isolated myopathy

Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide range of clinical phenotypes, often involving multiple organ systems. We report two patients with isolated myopathy owing to novel mt-tRNA^Ala variants. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation studies (revealing statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres), hierarchical mutation segregation within patient tissues and decreased steady-state mt-tRNA^Ala levels all provide compelling evidence of pathogenicity. Interestingly, both patients showed very high-mutation levels in all tissues, inferring that the threshold for impairment of oxidative phosphorylation, as evidenced by COX deficiency, appears to be extremely high for these mt-tRNA^Ala variants. Previously described mt-tRNA^Ala mutations are also associated with a pure myopathic phenotype and demonstrate very high mtDNA heteroplasmy thresholds, inferring at least some genotype:phenotype correlation for mutations within this particular mt-tRNA gene.     

Psychological functioning of adults with cystic fibrosis

STUDY OBJECTIVES: The purpose of this study is to assess the psychological profiles of adult patients with cystic fibrosis (CF) and to investigate predictors of patients' psychological status. PATIENTS AND METHODS: Thirty-four adults with CF completed a battery of psychological testing including the Minnesota Multiphasic Personality Inventory-2, Beck Depression Inventory, and State-Trait Anxiety inventory. These were compared to health status data, including pulmonary function testing and nutritional status measures. RESULTS: As a group, adults with CF did not demonstrate significant levels of depression, anxiety, or other psychopathology. Results were not affected by age, sex, or severity of disease. Male gender predicted higher scores for depression and anxiety, and better lung functioning predicted less anxiety. Having a higher level of psychosocial support emerged as a strong predictor of better psychological functioning. CONCLUSIONS: Overall, adults with CF report relatively healthy psychological functioning. Better lung function and a strong social support system predicted better psychological functioning, which may have implications for clinical intervention.     

Luteinizing hormone differentially regulates the secretion of testicular oxytocin and testosterone by purified adult rat Leydig cells in vitro.

The aims of the present study were to determine whether Leydig cells in vitro synthesize oxytocin, and whether LH modulates the secretion of oxytocin by Leydig cells. Highly purified adult Leydig cells were prepared from adult rats and cultured for 3 days in the presence or absence of 0.1 ng/ml ovine LH, and media were changed daily. The total amount of oxytocin present in the culture was estimated by RIA of cell extracts before culture (day 0) and at the end of day 3 of culture and in media on days 1-3. The content of immunoreactive oxytocin in cell extracts on day 0 (3.4 +/- 1.2 pg/10(6) cells) was significantly lower than the total amount that had been released into the medium and was present in the cell extracts at the end of day 3 (+LH, 27.8 +/- 3.3; -LH, 16.5 +/- 2.7 pg/10(6) cells), suggesting that Leydig cells are able to synthesize and secrete oxytocin. This hypothesis was supported by the observation that oxytocin release into the medium was significantly reduced during a 3-h treatment of Leydig cells with the protein synthesis inhibitor cycloheximide (5 micrograms/ml for 3 h). The role of LH in regulating testosterone production by Leydig cells is well defined, but whether LH also regulates oxytocin is unknown. Therefore, the effects of LH on oxytocin and testosterone production by Leydig cells were compared. The production of both hormones was stimulated by increasing doses of LH (0.001-100 ng/ml), but no further rise in oxytocin release could be elicited with amounts of LH greater than 0.1 ng/ml. Testosterone production, however, continued to increase with doses of LH up to 100 ng/ml. Furthermore, the two hormones differed in the rate of their responses to both 3- and 12-h exposures to LH; testosterone secretion increased more rapidly than that of oxytocin. These data provide direct evidence that adult Leydig cells produce immunoreactive oxytocin, and that their production of this peptide is regulated by LH.