Nemaline myopathy of cats

An apparently inherited myopathy, characterized by the presence of large numbers of nemaline rods in skeletal muscle fibers, was investigated in five cats. Onset of signs varied from 6 months to 1.5 years of age and consisted of reluctance to move, jerky gait and muscle twitching, hyporeflexia, and muscle wasting, which was most prominent in the proximal muscles of the forelimbs. All of the cats, three males and two females, were from the same dam. In addition to the presence of rods, the myopathy was characterized by marked fiber size variation, with atrophy of type 1 and type 2a muscle fibers. In addition, there was infolding of the sarcolemma and fiber splitting. Ultrastructurally, the rods closely resembled those described in human nemaline myopathy.     

Dopamine-D1 and δ-opioid receptors co-exist in rat striatal neurons

Cocaine's enhancement of dopaminergic neurotransmission in the mesolimbic pathway plays a critical role in the initial reinforcing properties of this drug. However, other neurotransmitter systems are also integral to the addiction process. A large body of data indicates that opioids and dopamine together mediate emotional and reinforced behaviors. In support of this, cocaine-mediated increases in activation of dopamine D1 receptors (D1R) results in a desensitization of δ-opioid receptor (DOR) signaling through adenylyl cyclase (AC) in striatal neurons. To further define cellular mechanisms underlying this effect, the subcellular distribution of DOR and D1R was examined in the rat dorsolateral striatum. Dual immunoperoxidase/gold-silver detection combined with electron microscopy was used to identify DOR and D1R immunoreactivities in the same section of tissue. Semi-quantitative analysis revealed that a subset of dendritic cellular profiles exhibited both DOR and D1R immunoreactivities. Of 198 randomly sampled D1R immunoreactive profiles, 43% contained DOR. Similarly of 165 DOR-labeled cellular profiles, 52% contained D1R. The present data provide ultrastructural evidence for co-existence between DOR and D1R in striatal neurons, suggesting a possible mechanism whereby D1R modulation may alter DOR function.     

A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Symptoms and time to presentation and treatment in ocular melanoma: the Western Canada Melanoma Study

Reports on all ocular melanomas newly diagnosed between Apr. 1, 1979, and Mar. 31, 1981, were obtained from the cancer registries of British Columbia, Alberta, Saskatchewan and Manitoba. Of the 90 cases, 87 were in patients aged 20 to 79 years, 64 of whom were interviewed about their initial symptoms. Three symptoms--loss of part of the visual field (in 33% of patients), photopsia (in 20%) and blurred vision (in 20%)--emerged as the main indicators of disease. In 17% of cases the tumour was discovered as an incidental finding on ocular examination. The length of delay before consulting a physician was generally short in symptomatic patients, with 85% reporting that they saw a physician within 3 months of onset of the first symptom. Of the 30 patients who received definitive treatment 4 months or more after initial presentation, 13 were seen by general practitioners who delayed before referring the patient to an ophthalmologist. Continuing medical education is needed to ensure earlier referral to ophthalmologists by general practitioners of patients with ocular melanoma.     

Mortality among female registered nurses and school teachers in British Columbia

The mortality profile of female nurses and teachers in British Columbia (BC) was examined using age-standardized proportional mortality ratios (PMRs) calculated for the period 1950–1984. Lowered overall mortality among nurses was seen for degenerative heart disease and for cerebrovascular accidents. Significantly elevated PMR values were observed for cancer of the breast and ovary in nurses of age 20–65 years. PMRs were significantly elevated for cancer of the pancreas and leukemia among those age 20 years and older. Elevated values were also observed for motor vehicle accidents and suicide among nurses in both age groups. Lower than expected mortality from degenerative heart disease and cerebrovascular accidents was seen in working age teachers (age 20–65 years). However, elevated PMRs were detected for carcinoma of the colon, breast, endometrium, brain, and melanoma. Among those 20 years and over, significantly elevated PMRs were also observed for cancers of the ovary and other digestive organs. Elevated PMRs were found for motor vehicle and aircraft accidents. Mortality from cirrhosis of the liver was lower than anticipated in both teachers and nurses. A number of significant PMRs declined when deaths of “homemakers” were withdrawn from the comparison group used to generate PMR values, suggesting that risk of death from various causes among women working outside the home differ from those seen in women who are predominantly in the home.     

Evidence for P2-purinoceptors on human osteoblast-like cells.

ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions.