Thymic cysts in mediastinal Hodgkin disease

Three cases of proved thymic cysts associated with mediastinal Hodgkin disease are presented. Two illustrate regression of lymphoma with chemotherapy but persistence of thymic cysts. The third case demonstrates a thymic cyst in untreated Hodgkin disease. These cases suggest that such cysts are probably neither coincidental with nor a consequence of therapy but are probably related to initial thymic involvement by Hodgkin disease.     

Ergotamine absorption and toxicity.

Adverse reactions to ergotamine were noted in 16 out of 41 studies in which therapeutic doses of the drug were given to normal, healthy volunteers. In 17 of the studies 0.25 mg ergotamine was given by injection, 6 i.v. and 11 i.m., in 20 studies 2 mg ergotamine was given by mouth, and 4 subjects received 2 mg ergotamine by suppository. Plasma and urinary ergotamine was measured by radio-immunoassay. Adverse reactions were significantly more frequent in subjects in whom plasma ergotamine exceeded 1.8 ng/ml. Pharmacokinetic data derived from the study are presented and their relevance to the therapeutic use of ergotamine are discussed.     

Transmission blocks: clinical and biological rationales

This paper describes the clinical and biological rationales for the use of transmission blocks. Clinical advantages over the use of full-thickness blocks applied part way through the course of therapy include the use of only one set of fields, blocks, and beam calculations, and less complex chart recording. There is a net saving in time required for the preparation and treatment of the patient. There is also a quality assurance advantage since the impact of a potential error in block positioning is reduced. In terms of biological advantages, it is demonstrated that the linear-quadratic iso-effect model can be applied to predict an improvement of up to 10% in the therapeutic ratio if transmission blocks are used instead of full-thickness blocks.     

Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina

Retinal neural transmission represents a key function of the eye. Identifying the molecular components of this vital process is helped by studies of selected human genetic eye disorders. For example, mutations in the calcium channel subunit gene CACNA1F cause incomplete X-linked congenital stationary night blindness (CSNB2 or iCSNB), a human retinal disorder with abnormal electrophysiological response and visual impairments consistent with a retinal neurotransmission defect. To understand the subcellular basis of this retinal disorder, we generated a mouse with a loss-of-function mutation by inserting a self-excising Cre-lox-neo cassette into exon 7 of the murine orthologue, Cacna1f. Electroretinography of the mutant mouse revealed a scotopic a-wave of marginally reduced amplitude compared with the wild-type mouse and absence of the post-receptoral b-wave and oscillatory potentials. Cone ERG responses together with visual evoked potentials and multi-unit activity in the superior colliculus were also absent. Calcium imaging in Fluo-4 loaded retinal slices depolarized with KCl showed 90% less peak signal in the photoreceptor synapses of the Cacna1f mutant than in wild-type mice. The absence of post-receptoral ERG responses and the diminished photoreceptor calcium signals are consistent with a loss of Ca((2+)) channel function in photoreceptors. Immunocytochemistry showed no detectable Ca(v)1.4 protein in the outer plexiform layer of Cacna1f-mutant mice, profound loss of photoreceptor synapses, and abnormal dendritic sprouting of second-order neurons in the photoreceptor layer. Together, these findings in the Cacna1f-mutant mouse reveal that the Ca(v)1.4 calcium channel is vital for the functional assembly and/or maintenance and synaptic functions of photoreceptor ribbon synapses. Moreover, the outcome of this study provides critical clues to the pathophysiology of the human retinal channelopathy of X-linked incomplete CSNB.     

Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells

Renal proximal tubule cells are responsible for the reabsorption of proteins that are present in the tubular lumen. This occurs by receptor-mediated endocytosis, a process that has a requirement for some GTP-binding proteins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase used for the therapeutic reduction of cholesterol-containing plasma lipoproteins. However, they can also reduce intracellular levels of isoprenoid pyrophosphates that are derived from the product of the enzyme, mevalonate, and are required for the prenylation and normal function of GTP-binding proteins. The hypothesis that inhibition of HMG-CoA reductase in renal proximal tubule cells could reduce receptor mediated-endocytosis was therefore tested. Five different statins inhibited the uptake of FITC-labeled albumin by the proximal tubule-derived opossum kidney cell line in a dose-dependent manner and in the absence of cytotoxicity. The reduction in albumin uptake was related to the degree of inhibition of HMG-CoA reductase. Simvastatin (e.g., statin) inhibited receptor-mediated endocytosis of both FITC-albumin and FITC-beta(2)-microglobulin to similar extents but without altering the binding of albumin to the cell surface. The effect on albumin endocytosis was prevented by mevalonate and by the isoprenoid geranylgeranyl pyrophosphate but not by cholesterol. Finally, evidence that the inhibitory effect of statins on endocytosis of proteins may be caused by reduced prenylation and thereby decreased function of one or more GTP-binding proteins is provided. These data establish the possibility in principle that inhibition of HMG-CoA reductase by statins in proximal tubule cells may reduce tubular protein reabsorption.     

Modeled evidence of force reduction at the extensor carpi radialis brevis origin with the forearm support band

PURPOSE: Although the forearm support band has been hypothesized to reduce force and thus inflammation and degeneration at the extensor carpi radialis brevis (ECRB) origin, little evidence exists to support an actual effect. We present both a cadaveric and clinical model that show the effect and principles of the forearm support band. METHOD: The cadaver model measured forces at the ECRB origin as various pressures were applied to the forearm support band and while the ECRB tendon was loaded distally. For clinical correlation support band pressure during rest and activity was measured in healthy individuals. RESULTS: Our results revealed an increased forearm support band effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation the support band pressure during activity was measured in 21 healthy volunteers while controlling for the application pressure in 2 common support band designs. This resulted in activity pressures ranging from 43 to 192 mm Hg dependent on the starting pressure of application. CONCLUSIONS: Although further clinical evaluation is necessary to determine the most appropriate clinical indications and application pressures for the forearm support band these combined results suggest that the forearm support band may be most effective when applied to 30 to 50 mm Hg at rest, resulting in up to 120 mm Hg pressure during activity. According to our model this would result in a force reduction at the ECRB origin of approximately 13% to 15% throughout a range of activity levels.     

Traumatic unilateral avulsion of the anterior superior and inferior iliac spines with anterior dislocation of the hip: a case report

A sixteen-year-old boy involved in a high-speed motor vehicle accident sustained an anterior hip dislocation and avulsion of the anterior ilium extending from the anterior superior iliac spine to the anterior inferior iliac spine. The hip was emergently reduced, and further imaging was obtained to evaluate the bony injury. Computed tomography confirmed the presence of a large displaced bony fragment representing avulsion of the anterior superior and inferior iliac spines and a smaller fragment from the reflected head of the rectus femoris. The patient underwent open reduction and internal fixation of the ilium two days after the initial injury. Postoperatively, he was allowed to bear weight as tolerated with crutches but to avoid active hip flexion. He went on to an uneventful recovery, and at last report (approximately six months after injury), he had returned to full activity. An extensive review of the literature failed to show a similar injury of ipsilateral avulsion of the anterior superior and inferior iliac spines and reflected head of the rectus femoris.