[Brain metastases from colorectal cancer]. / Hjernemetastaser ved kolorektal cancer.

Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time.

Efficacy of transluminal angioplasty for the management of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: Transluminal angioplasty has become a widely used adjunct therapy to medical management of symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH). Despite anecdotal reports of universal, angiographically confirmed reversal of vasospasm and high rates of clinical improvement, no rigorous examination of the efficacy of this procedure has been conducted. In this study the authors assess the efficacy of the aforementioned procedure. METHODS: Thirty-eight patients enrolled as part of the North American trial of tirilazad in aneurysmal SAH underwent transluminal angioplasty for symptomatic cerebral vasospasm. Fifty-three percent of these patients showed good recovery or moderate disability based on their 3-month Glasgow Outcome Scale score. Among the 38 patients who underwent angioplasty, the severity and type of vasospasm, use of papaverine in addition to balloon angioplasty, timing of treatment, and dose of study drug did not have an effect on the outcome. The results of their neurological examinations improved in only four of the 38 patients immediately after the procedure. A conditional logistic regression analysis was performed in which these patients were compared with individuals matched for age, sex, dose of study drug, admission neurological grade, and modified Glasgow Coma Scale score at the time of angioplasty. No effect on favorable outcomes was found for this procedure. CONCLUSIONS: Transluminal cerebral angioplasty is very effective in reversing angiographically confirmed vasospasm, and anecdotal reports of its clinical utility are numerous. However, in this report the authors conclude that its superiority to medical management for symptomatic cerebral vasospasm is questionable.

Sex hormones and lipoproteins in adolescent male offspring of parents with premature coronary heart disease and a control group.

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.

Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm.

OBJECTIVE: We examined the therapeutic benefits of intra-arterially administered papaverine for treatment of symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). Recent advances in microcatheter technology have facilitated endovascular approaches to vessels experiencing vasospasm after SAH. However, despite numerous encouraging anecdotal reports, no rigorous examination of the efficacy of these procedures has been published. Intra-arterial infusion of papaverine has become part of the standard management of vasospasm at some centers. METHODS: We examined a series of 31 patients undergoing papaverine infusion for the treatment of symptomatic vasospasm after SAH. The patients were a subgroup of the series enrolled in the North American Trial of Tirilizad for Aneurysmal Subarachnoid Hemorrhage. These individuals were matched with patients from the same trial who exhibited similar clinical characteristics (including the degree of vasospasm and the modified Glasgow Coma Scale scores measured at the time of admission and on the day of papaverine infusion) but received medical management alone for vasospasm. RESULTS: Logistic regression analysis comparing these two groups showed no statistical difference in the 3-month Glasgow Outcome Scale scores between patients receiving papaverine and control subjects (58% favorable outcomes for control subjects versus 45% for patients receiving papaverine). CONCLUSION: Although isolated series documenting clinical successes have prompted the increased use of papaverine as a treatment for vasospasm after SAH, this series suggests that, as it is currently being used, the drug does not provide added benefits, compared with medical treatment of vasospasm alone. This result does not preclude the possibility that alterations in the timing of or indications for drug treatment might produce beneficial effects.

Human bone bank allografts stimulate bone resorption and inhibit proliferation in cultures of human osteoblast-like cells.

Incorporation of a frozen human bone allograft requires osteoclast activity and ingrowth of recipient osteoblast precursors. We examined the effects of allografts on human osteoblasts. Allografts stimulated a release of factors from normal human osteoblast-like cells, capable of inducing osteoclastic bone resorption in vivo. Further allografts inhibited osteoblast proliferation in cultures. The response was detectable within 4 days of culture and was still present after 3 weeks. Devitalized bone autografts had a similar effect. This suggests that bone bank grafts may induce a resorptive reaction at the recipient site by stimulating release of factors from osteoblasts capable of inducing osteoclastic resorption. The storage temperature was crucial for preservation of the response, since the activity was lower in allografts stored for 6 months at -20 degrees C than in those stored at -80 degrees C.

Endovascular treatment for symptomatic cerebral vasospasm after subarachnoid hemorrhage: transluminal balloon angioplasty compared with intraarterial papaverine.

The authors retrospectively evaluated the short-term neurological improvement of 69 patients undergoing endovascular treatment for symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The patient group observed here is a subset of patients enrolled in the multicenter North American Trial of Tirilazad in SAH. Thirty-one patients were treated with intraarterial administration of papaverine (IAP). Fourteen patients were only treated with transluminal balloon angioplasty (TBA), and 24 patients received a combination of angioplasty and papaverine. The purpose of this study was to compare the effects of IAP and TBA on short-term clinical improvement of patients. Daily clinical staging with the modified Glasgow Coma Scale and every-other-day transcranial Doppler (TCD) measurements allowed for a close investigation of the clinical course. Furthermore, this study was designed to investigate the effects of treatment timing on short-term outcome. Although TCD studies demonstrated a decrease in flow velocities in the middle cerebral artery in both treatment groups, indicating a vasodilating effect of both treatment modalities (dv = -18.4 cm/second for papaverine, dv = -26.04 cm/second for angioplasty; p = 0.5509), there was no significant difference in clinical improvement at Days 1 and 4 postprocedure (p = 0.1996). Neither of the two treatment forms showed an effect of therapy timing on neurological outcome. Neither IAP nor TBA was correlated with a high percentage of short-term neurological improvement. The authors discuss reasons why those procedures may result in limited clinical change.

Removable partial denture design considerations where periodontally compromised teeth exist.

Restoration of a periodontally compromised dental arch with a removable partial denture may require one or more design modifications. Multiple rests ensure that adequate vertical support remains in the event primary abutment teeth are lost. An open or closed base can be strategically placed in the maxillary major connector to facilitate the replacement of subsequently lost teeth. The location of finish lines can be modified to provide a smoother resin-to-metal transition when posterior teeth are lost. Wire direct retainers that provide more physiologically acceptable clasping of compromised teeth and that are easily adjusted and added to the prosthesis should be considered.

The rat subcutaneous air sac model: a new and simple method for in vivo screening of antiangiogenesis.

An experimental rat model, the Subcutaneous Air Sac (SAS) model, was developed to provide an animal model in which neo-vascularization can be easily assessed in situ and quantified using a radiolabelled plasma marker. The SAS model was designed to replace a previous model where neovascularization was induced by chemical injury of rat or rabbit cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model the air sac replaces the cornea as a transparent avascular substratum in which vascularization can be observed. The air sac is induced by injection of air subcutaneously on the back of the animal. After 8 to 10 days a sufficient air sac has been established. The animal is anaesthesized and by a minor operation the cellulose sponge is implanted upon the air sac under the skin. The vasoproliferative effect of the cellulose sponge causes formation of new vessels which are macroscopically visible 10 days after implantation. The ability of the in vivo SAS model to show an antiangiogenic effect of a systemically applied test compound was investigated using the fumagillin analogue TNP-470 (ochloro-acetylcarbamoyl)-fumagillol) as a positive control at dose levels of 0, 1, 2.5, 5 and 10 mg/kg/day given subcutaneously for 10 days. The neo-angiogenesis was scored both in situ using a subjective point system and by measuring the 125I-activity of the implant and the membrane after an intravenous injection of 125I-labelled antibodies. The neo-angiogenesis was reduced by approximately 45-50% in animals treated with 5 or 10 mg/kg/day of TNP-470 compared to animals treated with the vehicle. The animals treated with 10 mg/kg/day TNP-470 showed signs of toxicity. The SAS model is considered highly relevant for in vivo testing of potential antiangiogenic drugs on humane grounds. The high reproducibility, the low cost and the technical simplicity of the method makes it attractive.

Differential coupling of alpha1-adrenoreceptor subtypes to phospholipase C and mitogen activated protein kinase in neonatal rat cardiac myocytes.

Activation of cardiac alpha1-adrenoreceptors has a number of physiological effects. Ascribing these effects to a specific alpha1-adrenoreceptor subtype first requires the elucidation of the subtypes that are present in the tissue of interest. In the present study, mRNA transcripts for the alpha1A, alpha1B and alpha1D-adrenoreceptor subtypes were detected in cultured neonatal rat cardiac myocytes, using reverse transcriptase-polymerase chain reaction analysis. However, binding sites for only the alpha1A and alpha1B-adrenoreceptor subtypes were detected in cultured neonatal rat cardiac myocytes, using competition binding analysis with a variety of alpha1 selective receptor antagonists. Phenylephrine-stimulated phosphatidylinositol hydrolysis was inhibited by alpha1 selective receptor antagonists with affinities consistent with the alpha1A-adrenoreceptor subtype, whereas phenylephrine-induced activation of the mitogen activated protein kinase cascade was inhibited by these same antagonists with affinities more closely resembling the alpha1B-adrenoreceptor subtype. In the case of both signaling pathways, the alpha1D selective receptor antagonist, BMY 7378, exhibited affinities suggestive of the relative absence of a alpha1D-adrenoreceptor subtype. Thus, despite the presence of mRNA transcripts for all three alpha1-adrenoreceptor subtypes, only the alpha1A and alpha1B-adrenoreceptor subtypes were expressed and functionally coupled at detectable levels in neonatal rat cardiac myocytes. Of particular interest, phenylephrine-induced activation of the mitogen activated protein kinase cascade appears to be mediated by a subtype resembling most closely the pharmacological profile of the alpha1B-adrenoreceptor subtype.

G-protein alpha subunit Gi(alpha)2 mediates erythropoietin signal transduction in human erythroid precursors.

Erythropoietin induces a dose-dependent increase in cytosolic calcium in human erythroblasts that is mediated by a voltage-independent Ca2+ channel. Inhibition of this response to erythropoietin by pertussis toxin suggests involvement of guanine nucleotide-binding regulatory proteins (G-proteins). The role of G-proteins in regulation of the erythropoietin-modulated Ca2+ channel was delineated here by microinjection of G-protein modulators or subunits into human erythroid precursors. This is the first report on the use of microinjection to study erythropoietin signal transduction in normal precursor cells. Fura-2 loaded day-10 burst-forming units-erythroid-derived erythroblasts were used for microinjection and free intracellular calcium concentration ([Ca(i)]) was measured with digital video imaging. BCECF (1,2',7'-bis(2-carboxyethyl)-5-(and -6-)-carboxyfluorescein) was included in microinjectate, and an increase in BCECF fluorescence was evidence of successful microinjection. Cells were microinjected with nonhydrolyzable analogues of GTP, GTPgammaS or GDPbetaS, which maintain the alpha subunit in an activated or inactivated state, respectively. [Ca(i)] increased significantly in a dose-dependent manner after microinjection of GTPgammaS. However, injection of GDPbetaS blocked the erythropoietin-induced calcium increase, providing direct evidence that activation of a G-protein is required. To delineate which G-protein subunits are involved, alpha or betagamma transducin subunits were purified and microinjected as a sink for betagamma or alpha subunits in the erythroblast, respectively. Transducin betagamma, but not alpha, subunits eliminated the calcium response to erythropoietin, demonstrating the primary role of the alpha subunit. Microinjected antibodies to Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3, blocked the erythropoietin-stimulated [Ca(i)] rise, identifying Gi(alpha)2 as the subunit involved. This was confirmed by the ability of microinjected recombinant myristoylated Gi(alpha)2, but not Gi(alpha)1 or Gi(alpha)3 subunits, to reconstitute the response of pertussis toxin-treated erythroblasts to erythropoietin. These data directly demonstrate a physiologic function of G-proteins in hematopoietic cells and show that Gi(alpha)2 is required in erythropoietin modulation of [Ca(i)] via influx through calcium channels.

A simplified procedure for boxing elastomeric impressions.

Although it is taught in most dental schools, the boxing of impressions is often avoided by dentists after their graduation. This article presents a simple and efficient procedure that makes boxing impressions more acceptable. Irreversible hydrocolloid and the subsequent stone mix are confined with a magnetic boxing strip that can be easily removed and replaced. The procedure is described for boxing edentulous and partially edentulous altered cast impressions made with elastomeric impression materials.

Gßγ-Mediated signaling in the heart: Implications of ß and γ subunit heterogeneity.

A family of G proteins, composed of α, ß, and γ subunits, plays a central role in coupling receptors to a variety of enzymes and ion channels. In the cardiovascular system, G proteins are involved in coupling receptors for epinephrine, norepinephrine, acetylcholine, adenosine, angiotensin II, and endothelin to regulation of adenylyl cyclases, phospholipases, and ion channels. For many years, the classic view has been that G protein α subunits provide the requisite specificity for receptor and effector interactions. Recent advances, however, have revealed that the ß and γ subunits also play prominent roles in transducing information from receptors to the appropriate effectors. With the identification of multiple subtypes of ß and γ subunits in the heart, questions are raised regarding their respective roles in signal transduction processes regulating cardiac function.

Surgical approaches for the correction of unstable thoracolumbar burst fractures: a retrospective analysis of treatment outcomes.

The authors retrospectively studied 49 nonparaplegic patients who sustained acute unstable thoracolumbar burst fractures. All patients underwent surgical treatment and were followed for an average of 27 months. All but one patient achieved solid radiographic fusion. Three treatment groups were studied: the first group of 16 patients underwent anterior decompression and fusion with instrumentation; the second group of 27 patients underwent posterior decompression and fusion; and the third group of six patients had combined anterior-posterior surgery. Prior to surgical intervention, these groups were compared and found to be similar in age, gender, level of injury, percentage of canal compromise, neurological function, and kyphosis. Patients treated with posterior surgery had a statistically significant diminution in operative time and blood loss and number of units transfused. There were no significant intergroup differences when considering postoperative kyphotic correction, neurological function, pain assessment, or the ability to return to work. Posterior surgery was found to be as effective as anterior or anterior-posterior surgery when treating unstable thoracolumbar burst fractures. Posterior surgery, however, takes the least time, causes the least blood loss, and is the least expensive of the three procedures.

Custom tinting denture bases by visible light cure lamination.

A urethane dimethacrylate and tinting powder lamination, chemically bonded to a methyl methacrylate denture base, produces a natural-appearing distribution of the tints. The characterization is protected by a hard, clear layer of urethane. Procedures are described that achieve this lamination either in the laboratory, before processing the dentures, or after the dentures have been fabricated.

Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

Tirilazad mesylate, a 21-aminosteroid free-radical scavenger, has been shown to ameliorate cerebral vasospasm and reduce infarct size in animal models of subarachnoid hemorrhage (SAH) and focal cerebral ischemia. In preparation for performing large-scale clinical trials in humans with aneurysmal SAH, the safety of varying doses of tirilazad was tested in a randomized, double-blind, vehicle-controlled, sequential dose-escalation study at 12 Canadian neurosurgical centers. Two hundred forty-five patients with an aneurysmal SAH documented by angiography were enrolled in the study sequentially within 72 hours of hemorrhage. The patients were assigned to one of three dosage tiers: receiving 0.6 mg/kg, 2 mg/kg, or 6 mg/kg tirilazad or vehicle per day intravenously in divided doses through Day 10 following the SAH. All patients also received oral nimodipine. No serious side effects of tirilazad treatment were identified at any of the three doses, despite close monitoring of hepatic and cardiac toxicity. A trend toward improvement in overall 3-month patient outcome was seen in the 2 mg/kg per day tirilazad-treated group compared to the outcomes in the vehicle-treated groups. We conclude that tirilazad mesylate is safe in SAH patients at doses up to 6 mg/kg per day for up to 10 days and is a promising drug for the treatment of patients with aneurysmal SAH.

Subunit expression of signal transducing G proteins in cardiac tissue: implications for phospholipase C-beta regulation.

In the heart, alpha-adrenergic, angiotensin II and endothelin signaling pathways modulate short-term changes in chronotropy and inotropy, and participate in the long-term control of cardiac growth. A shared feature of these signaling pathways is the stimulation of phosphatidylinositol (PI) turnover, which is thought to occur via G protein-mediated regulation of phospholipase C (PLC) activity. However, G protein subunits capable of regulating PLC activity have not been identified in different regions and cell types of the heart and members of the G protein-regulated PLC-beta isozyme family have not been documented in the heart. Using a battery of antipeptide specific antisera directed against the G protein alpha q, beta and gamma subunit families and against members of the PLC-beta, PLC-gamma and PLC-delta families, we demonstrated that heart tissues express the G protein alpha subunits alpha q and alpha 11, multiple G protein beta and gamma subunits, and PLC-beta 3, a phospholipase C isozyme regulated by either G protein alpha or beta gamma subunits. The degree of expression and distribution of these subunits differed between regions of the heart (atria versus ventricle) and changed with development. These data lay the ground work for future studies to determine the functional coupling of specific subsets of these components involved in receptor activation of PI turnover in the heart.