Surgery for asymptomatic carotid stenosis: a study of three patient subgroups

Increasing evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) differ in gastrotoxicity. This study aimed to compare the effects of a short-acting NSAID, tiaprofenic acid, with indomethacin on experimental gastric ulcer healing in a rat model. Similar anti-inflammatory and prostaglandin-inhibitory doses of indomethacin (1 mg/kg) and tiaprofenic acid (2 mg/kg) were administered to rats with acetic acid-induced ulcers. After 2 weeks treatment, rats were killed and ulcer size determined. In addition, histological sections of ulcers were assessed for ulcer contraction and mucosal regeneration. The degree of inhibition of prostaglandin E2 (PGE2) synthesis was 72% at 2 h after tiaprofenic acid and 64% at 2 h after indomethacin administration, respectively. Rats treated with indomethacin for 2 weeks had significantly larger ulcers, both macroscopically and microscopically, than controls. Rats treated with tiaprofenic acid for 2 weeks had ulcers of a similar size to those of controls. Indomethacin-treated ulcers showed a failure in mucosal regeneration. Tiaprofenic acid-treated ulcers had significantly more regeneration than indomethacin-treated ulcers. We conclude that tiaprofenic acid inhibits mucosal prostaglandin levels but does not inhibit experimental gastric ulcer healing. These findings suggest that inhibition of PGE2 synthesis is not the only factor in generating gastrotoxicity and that a shift to low gastrotoxic NSAID may be clinically worthwhile.     

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.     

Ultrasonically activated shears in thyroid surgery

BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both safe and fast devices in laparoscopic surgery. We studied whether the use of UAS would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed by one senior endocrine surgeon between December 1996 and February 1997, were retrospectively matched, with patients operated on by the same surgeon using the conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of lobectomies could be matched. Mean operating time was 100 minutes for the patients operated on with the UAS and 154 minutes for the patients operated on with the conventional method. The mean operating time with the UAS was thus on average 64.6% of the operation time with the conventional method, with a 95% confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS: In this material the use of UAS reduced significantly operating time in thyroidectomies.     

Fibronectin fragments modulate human retinal capillary cell proliferation and migration

Capillary morphogenesis involves cell-cell and cell-matrix interactions. Proteases elaborated by capillary cells modify the extracellular matrix (ECM) to facilitate capillary tube formation. Previously, we detected the presence of fibronectin fragments (Fn-f) associated with the proform of matrix metalloprotease-2 (MMP-2) in conditioned medium of human retinal endothelial cells (HRECs). Association of this fragment to latent MMP-2 prevented autocatalytic activation of MMP-2, suggesting a modulatory role of Fn-f in MMP-2 activation. In this report, we examined the potential role of Fn-f on two processes involved in angiogenesis, proliferation and migration of vascular cells. The effects of Fn-f on proliferation were determined by DNA synthesis and cell counts. Their effects on migration were assessed using modified Boyden chambers. Seven Fn-f were tested on vascular cell migration and/or proliferation. Three Fn-f induced migration. Fn-f of 30-kDa and 120-kDa size positively affected proliferation of microvascular cells but not macrovascular cells. A 45-kDa gelatin binding fragment of Fn inhibited HREC proliferation but stimulated pericyte and smooth muscle cell proliferation. The potency of these fragments exceeded that of the known angiogenic growth factor, basic fibroblast growth factor (bFGF), on HREC migration. ECM components such as fibronectin may influence capillary morphogenesis by the generation of fragments that can modulate proliferation, migration, and protease activation. In the setting of diabetes, excess Fn is generated and is available for degradation. Thus, the production of Fn-f may be specifically relevant to the angiogenesis observed in proliferative diabetic retinopathy.     

Effect of bile/pancreatic secretions on absorption of radioactive or stable zinc. In vivo and in vitro studies

Biliary/pancreatic (B/P) secretions are a major component of endogenous secretions, and endogenously secreted Zn is a primary means of Zn homeostasis. This study examined whether B/P fluid alters the absorption/reabsorption of Zn and, in doing so, whether this contributes to homeostatic control of Zn. Animal experiments utilized rats fed 10 or 300 micrograms Zn/kg diet. An open-ended gut perfusion study in which 65Zn-labeled B/P fluid or 67Zn-labeled and digested diet found significantly decreased Zn absorption from B/P fluid. Although Zn absorption from both sources was less in animals fed diets higher in Zn, there was no interaction of treatment and diet. Further studies utilizing cultured human colon carcinoma cells (CACO-2) as in vitro models of gut enterocytes found that the presence of B/P fluid significantly decreased Zn retention and/or transport and resulted in a redistribution of cellular Zn after 1200 min of incubation. These studies show that a substance in B/P fluid can decrease the absorption of Zn and also suggest that dietary Zn and Zn associated with B/P secretions are absorbed from distinct pools. However, the lack of an interactive effect with diet, and the amount of time required to see differences in CACO-2 cells, suggest that differences in absorption are not a major contributor to Zn homeostasis.     

Isochoric specific heat of sulfur hexafluoride at the critical point: Laboratory results and outline of a spacelab experiment for the d1-mission in 1985

The specific heat at constant volume c_v shows a weak singularity at the critical point. Renormalization group techniques have been applied, predicting a universal critical behavior which has to be experimentally confirmed for different systems. In this paper an experiment is presented to measure the specific heat of SF₆ along the critical isochore (_c=0.737 g·cm^–3), applying a continuous heating method. The results cover a temperature span of –1.5×10^–2< <1.70×10^–2 [=(T–T _c)/T _c] and were strongly affected by gravity effects that emerge in the sample of 1-mm hydrostatic height near the critical point. Using regression analysis, data were fitted with functions of the form c _v/R=A × ¦¦^– + B for the one-phase state and c _v/R=A × ¦¦^– + B for the twophase state. Within their error bounds the critical values (==0.098, A/A=1.83) represent the measurements for the temperature span 3.5×10^{–5< ¦¦<2.0×10 –3}, in good agreement with theoretical predictions. In order to exclude density profiles in the specimen, which are unavoidable in terrestrial experiments due to the high compressibility of fluids at the critical point and the gravity force, a space-qualified scanning ratio calorimeter has been constructed, which will permit long-term c_v measurements under microgravity (-g) conditions. The experiment will be part of the German Spacelab mission in October 1985. The significant features of the apparatus are briefly sketched.Paper presented at the Ninth Symposium on Thermophysical Properties, June 24–27, 1985, Boulder, Colorado, U.S.A.