[Pneumatic tube system for blood products transport]. / Dispositif pneumatique pour le transport des produits sanguins labiles.

Blood product transport from blood bank to the patient care areas of hospitals is a key step in the transfusion process. The pneumatic tube system is now widely used in hospitals. Strict performance specifications must be respected to guarantee blood safety: robustness, easy to use and respect the constraints imposed to blood products. To secure the disposal of blood products ordered to a carrier (delivery step), a security device must be deployed (video camera, barcode reading, fax, chip), allowing in particular to limit the risk of addressing error when sending (in the case of device with several arrival stations) or picked up by the wrong carrier.

Plateletpheresis concentrates produced with the COMTEC cell separator: the French experience.

The latest generation of cell separators such as Trima (Gambro), Amicus (Baxter) and AS-TEC 204 (Fresenius), allow the collection of leucocyte-reduced platelet concentrates without secondary filtration. Fresenius has recently developed the COMTEC cell separator whose performance has been evaluated by several teams in France. This new cell separator is an improved version of the Fresenius AS-TEC 204 cell separator, designed to allow more efficient platelet collections. This study reports on the experience of six French teams (from Bordeaux, Clermont-Ferrand, Creteil, Dijon, Lille and Nancy) who obtained 696 leucocyte-reduced plateletpheresis concentrates in the course of collection using the new Fresenius COMTEC cell separator. All healthy volunteer donors fulfilled French selection criteria for platelet apheresis. Donors were eligible if they had suitable venous accesses, if their bodyweight was *50 kg and if their pre-apheresis platelet count was >150 x 10(9) l(-1). Between 4606 and 5229 ml of blood were processed. The mean volume of the platelet concentrates was between 439 and 493 ml (mean 460 +/- 63 ml). The platelet yield was of the order of 5.18 +/- 1.02 x 10(11) with only one platelet concentrate below the norm of 2 x 10(11) platelets (0.91 x 10(11)). No plausible explanation for this was found. The residual leucocyte levels conform to current norms. The platelet concentrates contained less than 1 x 10(6) leucocytes per concentrate (mean 0.233 +/- 0.150 x 10(6) leucocytes) in more than 97% of the components produced with >95% statistical confidence. The efficacy of the cell separator (52.44 +/- 7.35%) is comparable to that of other separators. The Fresenius COMTEC cell separator makes it possible to obtain leucocyte-reduced platelet concentrates which comply with current standards both in terms of platelet content and residual leucocyte level.

The combination of laser recanalization and endoluminal intubation in the palliation of malignant dysphagia.

Laser recanalization and endoluminal intubation have been combined to optimize the palliation of malignant dysphagia in 37 patients. Nine patients with an endoluminal tube in situ presented with secondary dysphagia due to tumour overgrowth. Patency of the prosthesis was restored in all patients by laser recanalization with no complications. Twenty-eight patients treated initially by laser recanalization required subsequent intubation. The indications were dysphagia secondary to external compression (n = 3), significant angulation (n = 9), tracheo-oesophageal fistula (n = 3), failure of laser recanalization (n = 8), poor palliation (n = 3) or a combination of these (n = 2). There were no complications associated with the insertion of the tube and all patients subsequently reported improved swallowing. Laser recanalization or endoluminal intubation in isolation provide adequate palliation in the majority of patients with malignant dysphagia. We have shown that the appropriate timed combination of these two modalities may optimize the palliation of dysphagia in patients in whom the primary treatment modality fails.

Mixed epithelial polyps in association with hereditary non-polyposis colorectal cancer providing an alternative pathway of cancer histogenesis.

A member of a hereditary non-polyposis colorectal cancer (HNPCC) family developed two colorectal cancers and multiple polyps within four years of a negative colonoscopic examination. One of the cancers was only 4 mm in diameter and showed the gross and endoscopic appearances of a de novo carcinoma. Microscopic examination of multiple levels revealed a mixed hyperplastic polyp/adenoma (mixed polyp) in contiguity with the cancer. The colon harboured additional polyps of which five were tubular adenomas, seven were hyperplastic polyps and seven were mixed polyps (architecturally compatible with hyperplastic polyps but with atypical cytology). Atypical features of the mixed polyps included tripolar mitoses, bizarre chromatin aggregations and multinucleation. One mixed polyp showed DNA microsatellite instability. Under the influence of the mutator defect, hyperplastic polyps may develop atypical or adenomatous features and show progression to carcinoma. Such an alternative morphogenetic pathway could explain the differing molecular and pathological profiles of cancers showing DNA microsatellite instability.

Colorectal neoplasms detected colonoscopically in at-risk members of colorectal cancer families stratified by the demonstration of DNA microsatellite instability.

This study compared colonoscopic findings in families meeting the Amsterdam criteria (A) for hereditary non-polyposis colorectal cancer (HNPCC) but stratified according to whether the familial cancers showed DNA microsatellite instability. DNA was extracted from paired samples of normal and cancer, and microsatellite instability was analysed at up to six loci. Families were termed replication error positive (RER+) when at least 50% of tumours tested per family were positive. Of 26 families studied 17 were RER+ and 9 were RER-. Cancers in the A/RER- families showed no right-sided predilection (P < 0.001). Colonoscopies have been performed on 182 at-risk members of A/RER+ families and 60 members of A/RER- families. More of the at-risk members of A/RER-families were found to have adenomas at colonoscopy (P = 0.095), but these were smaller than those of A/RER+ families (P = 0.19). The adenoma:carcinoma ratio was twice as high in A/RER- families (13:1) as in A/RER+ families (7:1). One of the A/RER- families had hyperplastic polyposis. The others do not appear to have attenuated familial adenomatous polyposis and are similar to the adenoma families or late-onset colorectal cancer families described by others. This study illustrates the importance of molecular technology in separating HNPCC from syndromes with overlapping phenotypes.

Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome.

A mother and five of her ten offspring developed colonic cancers, the mother and one of the offspring being younger than 50 years of age at diagnosis. Despite fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer (HNPCC), several features pointed towards the possibility that this represented a different syndrome of familial cancer. Most notable was the presence of large, multiple hyperplastic polyps and mixed polyps in four of the subjects whose pathology was available for review. In addition, three of the four subjects had cancers that were negative for DNA replication errors (RER-). The subject with an RER+ cancer had a second RER+ cancer and three adenomas, one in contiguity with the second cancer. This subject also had multiple, large hyperplastic polyps, thereby combining hyperplastic polyposis and a proneness to multiple RER+ tumours. One of the hyperplastic polyps was also RER+. Two of five young asymptomatic descendants have been found to harbour multiple colorectal polyps. It is suggested that giant hyperplastic polyposis is a new familial syndrome predisposing to colorectal cancer.

Cardioplegic protection of hearts with pre-arrest ischaemic injury: effect of glucose, aspartate, and lactobionate.

This study compared the cardioprotective effects of three oxygenated "extracellular" crystalloid cardioplegic solutions. These were MBS (containing glucose, aspartate, and lactobionate [GAL]), St. Thomas' Hospital No. 2 (STH), and modified STH (added glucose, aspartate, and lactobionate) (STHGAL). Isolated working rat hearts (45) were initially injured with 10 min of global normothermic ischaemia and then arrested for 4 hr at (30 degrees C) with multidose cardioplegia (2 min every 30 min). The hearts (n = 9 per group) were then reperfused for 7 min in the non-working mode and for a further 23 min in the working mode. MBS-treated hearts rapidly resumed spontaneous sinus rhythm (0.69 +/- 0.06 minutes) with nearly complete recovery of function (aortic flow 93.3 +/- 5.4%, cardiac output 95.7 +/- 3.6%, stroke volume 95.3 +/- 3.7%, heart rate 102.2 +/- 3.7%, and aortic pressure 88.3 +/- 3.2% of pre-ischaemic control values). With either STH or STHGAL these indices were significantly (p < 0.01) lower (aortic flow 25.5 +/- 10.4% or 69.5 +/- 6.5%, cardiac output 30.1 +/- 11.1% or 67.6 +/- 6.6%, aortic pressure 36.5 +/- 7.7% or 63.9 +/- 8.0%, respectively). Total lactate efflux (indicating glycolysis) during cardioplegia was increased (p < 0.01) by inclusion of GAL (MBS 63.7 +/- 1.8, STHGAL 68.7 +/- 2.2, STH 28.5 +/- 1.3 mumol/heart). Progressive increase in coronary vascular resistance was observed during STH-based cardioplegia but not during MBS-based. The improved recovery of function was associated with reduced depletion of adenosine triphosphate (MBS 9.44 +/- 0.79, STHGAL 8.21 +/- 1.00, STH 1.02 +/- 0.10 mumol/g dry wt), total adenine nucleotide pool (14.61 +/- 0.83, 16.81 +/- 0.85, 7.33 +/- 0.52 mumol/g dry wt) and energy charge (0.767 +/- 0.019, 0.620 +/- 0.037, 0.248 +/- 0.012) during arrest, and significantly (p < 0.01) better resynthesis during reperfusion (ATP: 66%, 16%, 40%; TAN: 64%, 22%, 43% of control respectively). These findings indicate that the novel cardioplegic solution MBS (US Pat. No. 5,290,766) provides better myocardial protection than STH in hearts with pre-arrest ischaemic injury not only by providing metabolic substrates but also because of its more appropriate balance of cations.

Diagnostic use of microsatellite instability in hereditary non-polyposis colorectal cancer.

50 families with a history of colorectal cancer were divided according to whether criteria for hereditary non-polyposis colorectal cancer (HNPCC) were fulfilled totally (A, n = 19) or partly (B, n = 31) and stratified by the demonstration that at least half the cancers tested per family were positive for DNA replication errors (RER+). Accepted clinical and pathological characteristics of HNPCC were found to cluster within 12 A/RER+ families in which the mean number of affected individuals per family was 10.1. Reliance upon clinical data alone may result in over-diagnosis of HNPCC, in small families who just meet the minimum criteria, whereas underdiagnosis is rare. The criteria could be refined by inclusion of RER status.

Microvascular incompetence and the failure of hearts to recover contractile function after cardioplegia.

The relationship between the development of microvascular incompetence and the loss of potential for functional recovery following cardioplegia was investigated using St. Thomas' Hospital No. 2 solution (STH) in isolated working rat hearts. Cardiac function was measured prior to cardioplegia and again after 30 min of reperfusion at 37 degrees C following 1, 2 or 4 h arrest at 30 degrees C (n=5). The hearts were then fixed by perfusion with 2.5% glutaraldehyde and then nuclear track emulsion was perfused as an intravascular marker of competent capillaries. Following cardioplegia for 1 h hearts showed 95.4% recovery of aortic flow in the working mode, and a high proportion of the capillaries in the subendocardial (84.6 +/- 2.3%), middle (94.6 +/- 3.0%) and subepicardial (89.1 +/- 4.9%) thirds of the left ventricular myocardium transmitted perfusate. Two hours arrest resulted in significantly diminished recovery of left ventricular function (aortic flow: 56.6 +/- 7.6% and aortic pressure: 64.4 +/- 2.5% and heart rate 56.0 +/- 23.1%). This loss of the remaining two thirds of the potential for functional recovery was associated with significant (P<0.02) reductions in the proportions of competent capillaries (subendocardial, middle and subepicardial thirds to 10.9%, 19.2% and 14.2%, respectively). These non-functional capillaries had open lumina and showed no sign of structural alteration, obstruction or compression, although some focal collections of myocytes (<30%) showed evidence of reperfusion damage including contraction band necrosis. Despite reductions in microvascular competence overall, coronary flow rates (non-working) did not decline, suggesting shunting via large arterio-venous channels. It seems likely that the loss of the first third of the potential for rapid functional recovery following cardioplegia is due to loss of high energy phosphates, whereas the loss of the remaining two-thirds is associated with endothelial cell mediated constriction of small arterial vessels which produces the capillary incompetence demonstrated in this study.

Carotid endarterectomy for asymptomatic carotid artery stenosis: patients with severe bilateral disease a high risk subgroup.

Carotid endarterectomy if advised for asymptomatic disease must be associated with a low peri-operative morbidity and mortality and satisfactory long-term results. Over a 12 year period between 1978-1989 181 carotid endarterectomies were performed on 163 patients with asymptomatic carotid artery stenosis. There were 112 males and 51 females with a mean age of 64.9 years. All patients had a high-grade lesion (> 70% stenosis). The combined operative mortality and stroke rate was 2.8%. On long-term follow up six patients suffered a stroke. Only one patient however sustained a stroke in the same territory as the previously operated carotid artery. Four years following surgery 78% of patients were alive. Carotid restenosis or occlusion occurred in 8.3% of the remaining patients, all of whom were asymptomatic. All the immediate postoperative strokes occurred in patients with severe bilateral carotid artery disease. These patients with severe bilateral disease appear to constitute a high risk sub-group for peri-operative stroke. The role of 'normal pressure-hyperperfusion breakthrough' syndrome as the presumed aetiology of two of the postoperative cerebral haemorrhages is discussed.

Myocardial protection during prolonged ischaemic cardiac arrest: experimental evaluation of three crystalloid cardioplegic solutions.

The aim of this study is to define the cardioprotective effects (functional and metabolic) of our modified "extracellular" cardioplegic solution (MBS: containing glucose, aspartate and lactobionate), St. Thomas' Hospital No. 2 (STH) and Bretschneider's No. 3 (Bret) solutions during prolonged hypothermic ischaemia (20 degrees C, 6 hours) in the isolated working rat heart. hearts (n = 9-10 in each group) were arrested with, and exposed to, multidose reinfusion (2 minutes every 40 minutes interval) throughout the ischaemic period with cold (4 degrees C) MBS, STH or oxygenated (95% O2: 5% CO2) Bret. All MBS treated hearts resumed spontaneous regular sinus rhythm (0.51 +/- 0.01 minutes) of contraction during post-ischaemic reperfusion for 30 minutes at 37 degrees C with the complete recovery of all the functional indices (aortic flow: 87.4 +/- 3.4%, cardiac output: 94.1% +/- 3.3%, coronary flow: 101.8 +/- 4.1%, heart rate: 99.8 +/- 2.8% and aortic pressure: 105.7 +/- 4.6% of prearrest control values). In contrast, hearts protected with either STH or Bret showed the poor or no post-ischaemic recovery of cardiac pump function (aortic flow: 7.2 +/- 4.8% and 0%, respectively). Recovery of all other left ventricular function indices were also significantly (p < 0.001) decreased with increasing more hearts failing to regain function (MBS: 0/10, STH: 7/9 and Bret: 9/9). The efflux of lactate during 6 hours ischaemic arrest was increased [52.40 +/- 1.50 v 36.8 +/- 1.70 (STH) or 14.45 +/- 0.70 (Bret) mumol/heart, p < 0.001] and the progressive increase in the coronary vascular resistance was completely abolished in MBS treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (23.44 +/- 1.08 v 3.79 +/- 1.08 or 4.51 +/- 0.71 mumol/g dry wt), creatine phosphate (30.23 +/- 1.52 v 8.01 +/- 2.21 or 5.41 +/- 0.03 mumol/g dry wt) and guanosine triphosphate (2.26 +/- 0.23 v 0.24 +/- 0.11 or 0.59 +/- 0.07 mumol/g dry wt) during ischaemia, and total resynthesis after reperfusion (ATP: 92% v 36% or 25% and CP: 126% v 92% or 59% of control). These results indicate that the new cardioplegic solution, MBS can meet the metabolic demand of the ischaemic myocardium because of the greater synthesis of intramyocardial ATP and CP during cardioplegic arrest, provide substantially improved protection of hearts from injury and thus increase (double) the safe duration of cardiac arrest.

Protective effects of oxygenated St. Thomas' Hospital cardioplegic solution during ischaemic cardiac arrest: improved function, metabolism and ultrastructure.

The isolated working rat heart model was use to define the cardioprotective effects (function, metabolic and ultrastructure) of the oxygenated St. Thomas' Hospital No. 2 cardioplegic solution (STH) during lengthy, hypothermic ischaemia (20 degrees C, 4 hours and 5 hours). Hearts (n = 9 for each group) were arrested with and exposed to multidose reinfusion (2 min every 40 min interval) throughout the ischaemic period with the cold (4 degrees C) STH or oxygenated (95% O2:5% CO2) STH. Oxygenated STH significantly (p < 0.01) improved the postischaemic recovery of cardiac output from 49.5 +/- 11.1% to 96.8 +/- 1.5% (in 4 hours) and from 20.3 +/- 7.2% to 72.2 +/- 5% (in 5 hours). Other indices of functional recovery showed similar improved performance with the significant decrease in time from the onset of reperfusion to the return of regular sinus rhythm (57 +/- 8 v 495 +/- 150 s). The efflux of lactate during 5 hr ischaemic arrest was decreased (20.62 +/- 1.3 v 26.18 +/- 1.73 mumol/heart for oxygenated STH and STH, respectively, p < 0.05) and the progressive increase in the coronary vascular resistance was abolished in the oxygenated STH treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (14.49 +/- 2 v 3.3 +/- 0.19 mumol/g dry wt), creatine phosphate (24.61 +/- 3.47 v 7.48 +/- 1.34 mumol/g dry wt) and guanosine triphosphate (1.69 +/- 0.2 v 0.84 +/- 0.08 mumol/g dry wt) during ischaemia, total resynthesis after reperfusion (ATP: 103% v 36%, CP: 105% v 69% and GTP: 203% v 61% of control) and the total absence of myocardial cells and microvasculature injuries in ischaemic (non-reperfused) hearts. These results confirm that the provision of additional oxygen to the St. Thomas' Hospital solution (with 95% O2:5% CO2) can meet the metabolic demand of the ischaemic myocardium and thus increase the safe duration of cardiac arrest.

Subtotal cholecystectomy.

Subtotal cholecystectomy has been carried out on 11 patients during a 5-year period, constituting 3.8 per cent of cholecystectomies performed during this time. The indications were severe inflammation/fibrosis in six patients, portal hypertension in three and the Mirizzi syndrome in two patients. There were no deaths and only minor in-hospital morbidity. One patient developed a common bile duct stone 21 months after the operation. None of the remaining patients has to date developed postcholecystectomy sequelae (mean follow-up period 29 (range 1-62) months). Subtotal cholecystectomy is a safe, straightforward and definitive operation in patients for whom standard cholecystectomy could be dangerous, and is a more attractive proposition than cholecystostomy.

Diabetes, hyperinsulinaemia, and coronary risk factors in Bangladeshis in east London.

Immigrants from the Indian subcontinent (South Asians) in England and Wales have higher morbidity and mortality from coronary heart disease than the general population; this seems to apply to both Hindus and Muslims. Studies in north west London and Trinidad found that the increased risk of coronary heart disease in Indians was not explained by dietary fat intakes, smoking, blood pressure, or plasma lipids. In the present study the distribution of coronary risk factors was measured in an East London borough where the mortality and attack rate from coronary heart disease are higher in the Asian population, predominantly Muslims from Bangladesh, than in the rest of the population. In a sample of 253 men and women aged 35-69 from general practice, mean plasma cholesterol concentrations were lower in Bangladeshi than in European men and women. Mean systolic blood pressures were 10 mm Hg lower in Bangladeshis. Plasma fibrinogen concentrations were similar in Bangladeshis and Europeans and factor VII coagulant activity was lower in Bangladeshi than in European men. In contrast with the findings in Hindus in north west London, smoking rates were high in Bangladeshi men and the ratio of polyunsaturated fatty acids to saturated fatty acids in plasma lipids was lower in Bangladeshis than in Europeans. Diabetes was three times more common in Bangladeshis than in Europeans and serum insulin concentrations measured after a glucose load were twice as high in Bangladeshis. High insulin concentrations in Bangladeshis were associated with high plasma triglyceride and low high-density lipoprotein cholesterol concentrations. Insulin resistance, leading to diabetes, hyperinsulinaemia, and secondary lipoprotein disturbances, is a possible mechanism for the high rates of coronary heart disease in South Asians in Britain and overseas.

Effects of beta-agonists on b- and c-waves implicit for adrenergic mechanisms in cat retina.

Nylidrin (buphenine) is a beta-adrenergic agonist known to dilate peripheral vessels and used therapeutically in retinal degeneration and glaucoma. We studied retinal function under beta-agonists in arterially perfused cat eyes and observed a dose-dependent, reversible increase in b-wave amplitude and a decrease in c-wave amplitude in concentrations from 4.5 to 120 microM. A half maximal response was obtained at 40 to 50 microM. The optic nerve response to light showed dose-dependent reversible changes under nylidrin. Standing potential, light peak, intraocular pressure, vascular resistance, and diameter of or retinal vessels showed no consistent changes under nylidrin. The effect were inhibited by each of the beta-blocking agents propranolol, ICI 118, and oxprenolol (in sequence of decreasing potency). Another potent beta 2-agonist, clenbuterol, was used to determine the extent to which the responses to nylidrin were due to beta-receptor-mediated action. Clenbuterol had similar effects on the b-wave and optic nerve response at slightly higher concentrations (30 200 microM) but more variable effects on the c-wave. The data are interpreted as functional evidence that beta-adrenergic mechanisms are involved in retinal signal processing. This concept is corroborated by identification of beta-adrenergic binding sites in cat retina (Bruinink et al., 1986).

Effects of buphenine (nylidrin) on the perfused mammalian eye.

Buphenine (nylidrin), a beta-adrenergic agonist, is used therapeutically for its vasodilating effect on the peripheral circulation and possibly on the cerebral circulation as well. In spite of its ophthalmic usage in degenerative retinal disease and glaucoma, buphenine's ocular effects and their mechanisms are not sufficiently established. Consequently, we studied the action of 4.5-120 microM buphenine in isolated, arterially perfused cat eyes, and then used light-evoked electrical signals, perfusion flow rates and the diameters of the retinal vessels as parameters for the drug's effect. Our findings showed that buphenine induced a marked, dose-related, reversible increase in the amplitude of the electroretinogram (ERG) b-wave, a decrease in the c-wave, but no significant changes in the standing potential and light peak of the DC-ERG. The compound action potential of the optic nerve revealed dose-dependent and reversible changes in configuration. However, the flow of perfusate was not affected by the drug, and the diameter of retinal vessels did not change significantly. Our studies suggest that the interaction of buphenine with retinal adrenergic receptors is not related to the vasculature present but to elements involved in information processing. It is likely that these receptors are linked to neurons, since the beta-agonist affected the ERG b-waves as well as the compound action potential of the optic nerve.