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The effects of normal, low and high plasma concentrations of 1,25-(OH)[sub 2]vitamin D (1,25-(OH)[sub 2]D) combined with normal, low and high concentrations of plasma calcium on renal calbindin-D28k and intestinal calbindin-Dgk were examined in rats. We found that the expression of renal calbindin-D28k was significantly (P<0.05) increased by high levels of 1,25-(OH)[sub 2]D, but was not affected by a 50% reduction in 1,25-(OH)[sub 2]D. In contrast the intestinal calbindin-Dgk responded significantly (P<0.005) to both high and low 1,25-(OH)[sub 2]D levels. The effect of 1,25-(OH)[sub 2]D on intestinal calbindin-Dgk was modulated by plasma calcium concentrations. Increased plasma calcium levels did not affect the renal calbindin-D28k concentrations, but suppressed intestinal calbindin-D9k (P<0.05). The effect of calcium was not mediated by calciotropic hormones. This suggests the existence of a calcium-sensing mechanism in the proximal duodenum. It is concluded that intestinal calbindin-D9k is more sensitive than renal calbindin-D28k to changes in 1,25-(OH)[sub 2]D and that intestinal calbindin-Dgk in contrast to renal calbindin-D28k is sensitive to changes in plasma calcium concentrations. [ABSTRACT FROM AUTHOR]

Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety., (Copyright © 2020 Rouanet, Bolca, Bru, Claes, Cvejic, Girgis, Harper, Lavergne, Mathys, Pane, Pot, Shortt, Alkema, Bezulowsky, Blanquet-Diot, Chassard, Claus, Hadida, Hemmingsen, Jeune, Lindman, Midzi, Mogna, Movitz, Nasir, Oberreither, Seegers, Sterkman, Valo, Vieville and Cordaillat-Simmons.)

Microbubbles (MBs) stabilized by particle surfactants ( i.e ., Pickering bubbles) have better thermodynamic stability compared to MBs stabilized by small molecules as a result of steric hindrance against coalescence, higher diffusion resistance, and higher particle desorption energy. In addition, the use of particles to stabilize MBs that are typically used as an ultrasound (US) contrast agent can also introduce photoacoustic (PA) properties, thus enabling a highly effective dual-modality US and PA contrast agent. Here, we report the use of partially reduced and functionalized graphene oxide as the sole surfactant to stabilize perfluorocarbon gas bubbles in the preparation of a dual-modality US and PA agent, with high contrast in both imaging modes and without the need for small-molecule or polymer additives. This approach offers an increase in loading of the PA agent without destabilization and increased thickness of the MB shell compared to traditional systems, in which the focus is on adding a PA agent to existing MB formulations.

Emulsions are important in numerous fields, including cosmetics, coatings, and biomedical applications. A subset of these structures, oil-in-oil emulsions, are especially intriguing for water sensitive reactions such as polymerizations and catalysis. Widespread use and application of oil-in-oil emulsions is currently limited by the lack of facile and simple methods for preparing suitable surfactants. Herein, we report the ready preparation of oil-in-oil emulsions using 2D nanomaterials as surfactants at the interface of polar and nonpolar organic solvents. Both the edges and basal plane of graphene oxide nanosheets were functionalized with primary alkyl amines and we demonstrated that the length of the alkyl chain dictates the continuous phase of the oil-in-oil emulsions (i.e., nonpolar-in-polar or polar-in-nonpolar). The prepared emulsions are stable at least 5 weeks and we demonstrate they can be used to compartmentalize reagents such that reaction occurs only upon physical agitation. The simplicity and scalability of these oil-in-oil emulsions render them ideal for applications impossible with traditional oil-in-water emulsions, and provide a new interfacial area to explore and exploit.

Background: Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients with T2D. Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 randomised clinical trials that randomised 29 ,986 participants with T2D. We now report our updated review., Objectives: To assess the effects of targeted intensive glycaemic control compared with conventional glycaemic control in patients with T2D., Search Methods: Trials were obtained from searches of The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL (all until December 2012)., Selection Criteria: We included randomised clinical trials that prespecified targets of intensive glycaemic control versus conventional glycaemic control targets in adults with T2D., Data Collection and Analysis: Two authors independently assessed the risk of bias and extracted data. Dichotomous outcomes were assessed by risk ratios (RR) and 95% confidence intervals (CI). Health-related quality of life and costs of intervention were assessed with standardized mean differences (SMD) and 95% Cl., Main Results: Twenty-eight trials with 34,912 T2D participants randomised 18,717 participants to intensive glycaemic control versus 16,195 participants to conventional glycaemic control. Only two trials had low risk of bias on all risk of bias domains assessed. The duration of the intervention ranged from three days to 12.5 years. The number of participants in the included trials ranged from 20 to 11,140. There were no statistically significant differences between targeting intensive versus conventional glycaemic control for all-cause mortality (RR 1.00, 95% CI 0.92 to 1.08; 34,325 participants, 24 trials) or cardiovascular mortality (RR 1.06, 95% CI 0.94 to 1.21; 34,177 participants, 22 trials). Trial sequential analysis showed that a 10% relative risk reduction could be refuted for all-cause mortality. Targeting intensive glycaemic control did not show a statistically significant effect on the risks of macrovascular complications as a composite outcome in the random-effects model, but decreased the risks in the fixed-effect model (random RR 0.91, 95% CI 0.82 to 1.02; and fixed RR 0.93, 95% CI 0.87 to 0.99; P = 0.02; 32,846 participants, 14 trials). Targeting intensive versus conventional glycaemic control seemed to reduce the risks of non-fatal myocardial infarction (RR 0.87, 95% CI 0.77 to 0.98; P = 0.02; 30,417 participants, 14 trials), amputation of a lower extremity (RR 0.65, 95% CI 0.45 to 0.94; P = 0.02; 11,200 participants, 11 trials), as well as the risk of developing a composite outcome of microvascular diseases (RR 0.88, 95% CI 0.82 to 0.95; P = 0.0008; 25,927 participants, 6 trials), nephropathy (RR 0.75, 95% CI 0.59 to 0.95; P = 0.02; 28,096 participants, 11 trials), retinopathy (RR 0.79, 95% CI 0.68 to 0.92; P = 0.002; 10,300 participants, 9 trials), and the risk of retinal photocoagulation (RR 0.77, 95% CI 0.61 to 0.97; P = 0.03; 11,212 participants, 8 trials). No statistically significant effect of targeting intensive glucose control could be shown on non-fatal stroke, cardiac revascularization, or peripheral revascularization. Trial sequential analyses did not confirm a reduction of the risk of non-fatal myocardial infarction but confirmed a 10% relative risk reduction in favour of intensive glycaemic control on the composite outcome of microvascular diseases. For the remaining microvascular outcomes, trial sequential analyses could not establish firm evidence for a 10% relative risk reduction. Targeting intensive glycaemic control significantly increased the risk of mild hypoglycaemia, but substantial heterogeneity was present; severe hypoglycaemia (RR 2.18, 95% CI 1.53 to 3.11; 28,794 participants, 12 trials); and serious adverse events (RR 1.06, 95% CI 1.02 to 1.10; P = 0.007; 24,280 participants, 11 trials). Trial sequential analysis for a 10% relative risk increase showed firm evidence for mild hypoglycaemia and serious adverse events and a 30% relative risk increase for severe hypoglycaemia when targeting intensive versus conventional glycaemic control. Overall health-related quality of life, as well as the mental and the physical components of health-related quality of life did not show any statistical significant differences., Authors' Conclusions: Although we have been able to expand the number of participants by 16% in this update, we still find paucity of data on outcomes and the bias risk of the trials was mostly considered high. Targeting intensive glycaemic control compared with conventional glycaemic control did not show significant differences for all-cause mortality and cardiovascular mortality. Targeting intensive glycaemic control seemed to reduce the risk of microvascular complications, if we disregard the risks of bias, but increases the risk of hypoglycaemia and serious adverse events.

Background: Patients with type 2 diabetes mellitus (T2D) exhibit an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report a relationship between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients with T2D., Objectives: To assess the effects of targeting intensive versus conventional glycaemic control in T2D patients., Search Strategy: Trials were obtained from searches of CENTRAL (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL (until December 2010)., Selection Criteria: We included randomised clinical trials that prespecified different targets of glycaemic control in adults with T2D., Data Collection and Analysis: Two authors independently assessed the risk of bias and extracted data. Dichotomous outcomes were assessed by risk ratios (RR) and 95% confidence intervals (CI)., Main Results: Twenty trials randomised 16,106 T2D participants to intensive control and 13,880 T2D participants to conventional glycaemic control. The mean age of the participants was 62.1 years. The duration of the intervention ranged from three days to 12.5 years. The number of participants in the included trials ranged from 20 to 11,140. There was no significant difference between targeting intensive and conventional glycaemic control for all-cause mortality (RR 1.01, 95% CI 0.90 to 1.13; 29,731 participants, 18 trials) or cardiovascular mortality (RR 1.06, 95% CI 0.90 to 1.26; 29,731 participants, 18 trials). Trial sequential analysis (TSA) showed that a 10% RR reduction could be refuted for all-cause mortality. Targeting intensive glycaemic control did not show a significant effect on the risk of non-fatal myocardial infarction in the random-effects model but decreased the risk in the fixed-effect model (RR 0.86, 95% CI 0.78 to 0.96; P = 0.006; 29,174 participants, 12 trials). Targeting intensive glycaemic control reduced the risk of amputation (RR 0.64, 95% CI 0.43 to 0.95; P = 0.03; 6960 participants, 8 trials), the composite risk of microvascular disease (RR 0.89, 95% CI 0.83 to 0.95; P = 0.0006; 25,760 participants, 4 trials), retinopathy (RR 0.79, 95% CI 0.68 to 0.92; P = 0.002; 10,986 participants, 8 trials), retinal photocoagulation (RR 0.77, 95% CI 0.61 to 0.97; P = 0.03; 11,142 participants, 7 trials), and nephropathy (RR 0.78, 95% CI 0.61 to 0.99; P = 0.04; 27,929 participants, 9 trials). The risks of both mild and severe hypoglycaemia were increased with targeting intensive glycaemic control but substantial heterogeneity was present. The definition of severe hypoglycaemia varied among the included trials; severe hypoglycaemia was reported in 12 trials that included 28,127 participants. TSA showed that firm evidence was reached for a 30% RR increase in severe hypoglycaemic when targeting intensive glycaemic control. Subgroup analysis of trials exclusively dealing with glycaemic control in usual care settings showed a significant effect in favour of targeting intensive glycaemic control for non-fatal myocardial infarction. However, TSA showed more trials are needed before firm evidence is established., Authors' Conclusions: The included trials did not show significant differences for all-cause mortality and cardiovascular mortality when targeting intensive glycaemic control compared with conventional glycaemic control. Targeting intensive glycaemic control reduced the risk of microvascular complications while increasing the risk of hypoglycaemia. Furthermore, intensive glycaemic control might reduce the risk of non-fatal myocardial infarction in trials exclusively dealing with glycaemic control in usual care settings.

Background: In addition to the regulation of calcium homeostasis, vitamin D affects the cellular immune system, targets the TNF-alpha pathway and increases vasoconstrictor response to angiotensin II. We therefore examined the effect of 1,25-dihydroxy-vitamin D(3) on coagulation and organ failure in experimental sepsis in the rat., Methods: Three series of placebo-controlled studies were conducted. All rats were pre-treated with daily SC injections of 1,25-dihydroxy-vitamin D(3) 100 ng/kg or placebo vehicle for 3 days. In study 1, sepsis was accomplished by abdominal surgery comprising a coecal ligation and puncture with a 1,2 mm needle, or sham surgery. In study 2, the rats had a single IP injection of lipopolysaccharide from E. Coli 0111:B4 (LPS) 8 mg/kg, or placebo. In study 3, an hour-long IV infusion of LPS 7 mg/kg, or placebo was given., Results: All three models of sepsis showed significant effects on coagulation and liver function with reduced thrombocyte count and prothrombin time together with elevated ALT and bilirubin (p<0.05) as compared to controls. In study 1, the vitamin D treated rats maintained normal platelet count, whereas the vehicle treated rats showed a significant reduction (p<0.05). This effect of vitamin D on platelets was not found in the LPS-treated groups. We found no significant differences between vitamin D and placebo-treated rats with regards to liver function., Conclusion: The present data suggest a positive modulating effect of 1,25-dihydroxy-vitamin D(3) supplementation on sepsis-induced coagulation disturbances in the coecal ligation and puncture model. No such effect was found in LPS-induced sepsis.

Cyanide is a toxic compound which inhibits the cellular utilization of oxygen. A number of substances can give rise to cyanide intoxication, which in some cases may have a delayed onset. The symptoms are non-specific and reflect cellular hypoxia. Several strategies may be employed in the treatment. Hydroxycobalamine is an effective and non-toxic antidote. On the basis of a case story, the toxicology, symptoms and treatment of cyanide poisoning are discussed.

Calbindin-D28k is an intracellular protein with high affinity for calcium. In the kidney, this protein is exclusively localized in the distal tubule and in the proximal part of the collecting ducts. Functionally, calbindin-D28k is supposed to be involved in the regulation of the reabsorption of calcium and possibly magnesium in the distal nephron though the exact regulatory mechanisms are not yet known. Thus, several theories regarding the functional role of calbindin-D28k have been proposed: The carrier theory describes calbindin-D28k as a transport protein which binds calcium and then transports it from the luminal to the basolateralcell membrane. The buffer theory assumes that calbindin-D28k functions by binding calcium ions to prevent intracellular calcium concentrations from reaching toxic levels. The activator theory describes that calbindin-D28k increases the activity of calcium channels or the enzymatic activity of the Ca++-Mg++-ATPase in the luminal membrane and thereby increases the tubular reabsorption of calcium. The renal calbindin-D28k is dependent upon vitamin D. Pharmacological doses of the active vitamin D metabolite 1,25-(OH)2D increases the concentrations of renal calbindin-D28k, whereas the concentration of calbindin-D28k is low in conditions with reduced levels of circulating 1,25-(OH)2D. Likewise, plasma calcium concentrations, uremia and hypertension affect calbindin-D28k expression. However, several studies have rendered probable the effect of additional factors in the regulation of renal calbindin-D28k. The aim of the present dissertation therefore was to examine the regulation of renal calbindin-D28k in a series of physiological and pathophysiological conditions established in vivo in the rat. A possible correlation between hypertension and calbindin-D28k was examined in three models of experimental hypertension: the genetically defined spontaneous hypertensive rat, the salt-sensitive Dahl rat and the renovascular hypertensive rat. These three models clearly demonstrated three separate patterns in the calcium metabolism, but the studies were unable to support a role for calbindin-D28k in the development of hypertension. In all three models the development of hypertension caused an increased plasma 1,25-(OH)2D. This increase was accompanied by either unaltered or reduced levels of renal calbindin-D28k possibly secondary to a cellular resistance against 1,25-(OH)2D. Magnesium binds to calbindin-D28k with a relatively high affinity. The regulation of urinary magnesium excretion takes place in the distal tubule where calbindin-D28k is found in high concentrations. Therefore, a possible relation between magnesium and calbindin-D28k was examined. The studies demonstrated not previously known connections between magnesium intake, urinary magnesium excretion and renal calbindin-D28k which suggests that this protein is involved in the regulation of magnesium homeostasis by the kidney. Calcitonin increases the reabsorption of calcium in the distal tubule. Therefore, the effect ofcalcitonin on renal calbindin-D28k was examined both by eliminating the endogeneous calcitonin production by a selective thyroidectomy followed by an autotransplantation of the parathyroid glands and further by infusion of calcitonin. These studies demonstrated unchanged concentrations of renal calbindin-D28k. It was concluded that the increased calcium reabsorption induced by calcitonin in the distal tubule is not mediated by calbindin-D28k. Urinary calcium excretion is in part regulated by the action of PTH on calcium reabsorption in the distal nephron. Previous reports of increased expression of renal calbindin-D28k in uremic rats led us to suggest that secondary hyperparathyroidism associated with uremia induced the synthesis of renal calbindin-D28k. Therefore, the effect of PTH was examined in a study comprising selective parathyroidectomy and infusions of PTH, PTHrP, 1,25-(OH)2D and calcium. (ABSTRACT TRUNCATED)

Intraperitoneal injection of 1,25-(OH)2D3 4 micrograms/kg was given to 84 calcium- and vitamin D-repleted Wistar rats and samples of plasma, duodenal mucosa and renal tissue were taken after 0, 3, 6, 12, 24, 48 and 96 hr (n = 12 at each time interval). Plasma-ionized Ca increased after 6 hr, reached a maximum after 24 hr and returned to the initial values after 96 hr. The concentrations of renal calbindin-D28k and intestinal calbindin-D9k did not increase until 48 hr after injection and remained elevated until 96 hr after. Therefore, significantly elevated concentrations of the cytosolic calbindin-D were found at a time with normal values of plasma Ca. The present data suggest that calbindin-D does not alone increase the transcellular Ca transport and, therefore, supports the view that calbindin-Ds may serve as Ca buffer proteins.

We evaluated the effect of non-invasive nocturnal ventilation with the bi-level positive airway pressure (BiPAP) ventilator in 12 overweight patients with verified obstructive sleep apnoea syndrome (OSAS) and nocturnal hypercapnia. All patients exhibited subsequently less overnight CO2 accumulation (p < 0.0001), the desaturation event frequency was reduced (p < 0.002), daytime O2 tension rose (p < 0.001), daytime CO2 tension was reduced (p < 0.01), and apnoeas were eliminated. All symptoms characterising the syndrome, when present at the beginning of the therapy, were eliminated during the treatment. Patient compliance was high. This study showed that OSAS patients with hypercapnia can be effectively treated by BiPAP ventilation during sleep.

The present investigation examined the possible influence of urinary calcium excretion on the concentration of renal calbindin-D28k. Thiazide diuretics stimulate calcium transport across the epithelial cells of the distal tubule, which express calbindin-D28k in high concentrations. Calbindin-D28k is assumed to facilitate transcellular Ca diffusion. Reduced urine calcium excretion and increased urine output were induced in Wistar rats by infusion of bendroflume-thiazide 1 mg/kg/day. The two control groups had infusions of either furosemide 20 mg/kg/day or vehicle, n = 8 in each group. Urinary Ca excretion was reduced to 10% in the thiazide group and increased by 50% in the furosemide group. Renal concentrations of calbindin-D28 showed no difference between vehicle, thiazide- and furosemide-treated rats. No differences in plasma concentrations of calcium, magnesium, phosphorus, urea, PTH, calcitonin and 1,25-(OH)2D were found between the groups. The present study describes that urine calcium excretion selectively can be manipulated without accompanying changes in renal calbindin-D28k concentrations. The data, therefore, suggest that urinary calcium excretion is not a significant determinator of cytosolic concentrations of renal calbindin-D28k.

The present investigation was conducted to examine the effects of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) on renal calbindin-D28k in rats. Four groups of studies were performed: (1) parathyroidectomy (PTX) or a sham operation followed by infusion of 1,25-dihydroxyvitamin D (1,25[OH]2D) or vehicle; (2) infusions of PTH(1-34), PTH(1-84), 1,25(OH)2D, or vehicle; (3) infusion of PTHrP(1-34), PTHrP (1-86), PTH(1-34), or vehicle; and (4) injections of calcium or vehicle. PTX reduced renal calbindin-D28k levels even when plasma concentrations of 1,25(OH)2D were kept constant by infusion of 1,25(OH)2D. Infusions of PTH(1-34), PTH(1-84), and 1,25(OH)2D all increased renal calbindin-D28k and plasma calcium, whereas PTHrP(1-34) and PTHrP(1-86) increased renal calbindin-D28k before an increase of plasma calcium took place. Hypercalcemia induced by the injection of calcium did not affect the levels of renal calbindin-D28k. The present data suggest that PTH and PTHrP exert a direct effect on renal calbindin-D28k, which is not mediated by changes of 1,25(OH)2D or calcium.

Objective: To examine the impact of peritoneal dialysis catheter configuration, curled or straight catheter, on catheter survival and mechanical and infectious complications., Design: Prospective randomized trial., Setting: Department of Nephrology of a single university hospital., Patients: Seventy-two consecutive patients initiating peritoneal dialysis were randomized to receive either a single cuff straight catheter or a single cuff curled catheter, implanted by percutaneous technique., Results: Significantly higher (p < 0.01) survival rate of the curled as compared to the straight catheter. The difference in catheter survival was due to a significantly higher (p < 0.01) incidence of drainage failure associated with catheter tip migration of the straight catheter than of the curled catheter. No difference in infectious complication between the two types of catheters was seen. Catheter survival at 12 months was 77% for the curled catheter and 36% for the straight catheter., Conclusion: This study demonstrates superiority of the curled Tenckhoff peritoneal dialysis catheter survival as compared to the straight catheter. This difference in catheter survival is due to the higher displacement rate of the straight catheter.

Objective: To examine renal and intestinal calbindin-D in relation to calcium metabolic changes in three different models of experimental hypertension., Design: Spontaneously hypertensive rats (SHR), hypertension-prone Dahl salt-sensitive (Dahl-S) rats and the Goldblatt two-kidney, one clip rat model of renovascular hypertension were examined., Results: Both prehypertensive and hypertensive SHR had significantly lower concentrations of both renal calbindin-D28k and intestinal calbindin-D9k than Wistar control rats. This was accompanied by hypocalcaemia, hypomagnesaemia and increased plasma 1,25(OH)2 vitamin D levels. Induction of hypertension in Dahl-S rats reduced intestinal calbindin-D9k and increased plasma levels of 1,25(OH)2 vitamin D, while renal calbindin-D28k levels, plasma calcium levels and plasma magnesium levels were unchanged. Renovascular hypertension was associated with a significant increase in the intestinal calbindin-D9k, plasma 1,25(OH)2 vitamin D, parathyroid hormone and magnesium levels, while renal calbindin-D2k, plasma calcium and phosphorus levels were unaffected., Conclusions: These three models of experimental hypertension have clearly demonstrated three separate patterns in the regulation of renal and intestinal calbindin-D, which relate to different alterations of factors involved in calcium and magnesium metabolism. In all three models hypertension was accompanied by a significant increase in plasma concentrations of 1,25(OH)2 vitamin D. Only rats with renovascular hypertension showed increased intestinal calbindin-D9k levels, whereas reduced concentrations were found in the SHR and in the hypertensive Dahl-S rats. This indicates the existence of a resistance at the cellular level to 1,25(OH)2 vitamin D affecting the expression of calbindin-D in both SHR and Dahl-S rats.

The effect of ketamine on bronchospasm during mechanical ventilation was evaluated in a prospective, placebo-controlled, double-blind trial. Fourteen mechanically ventilated patients with bronchospasm were randomly allocated to either ketamine 1 mg/kg or saline placebo. In the ketamine-treated patients, PO2 increased from 10.5 (+/- 0.5) kPa to 16.4 (+/- 2.7) kPa (P < .05), whereas PO2 in the placebo-treated patients remained unchanged. The PCO2 was constant in the ketamine group, although it increased from 5.6 (+/- 0.9) kPa to 6.1 (+/- 0.9) kPa in the placebo group (P < .05). The pulmonary stethoscopic bronchospasm improved immediately after the administration of ketamine, whereas the thoracic compliance remained unchanged. In conclusion, the ketamine-treated patients showed an improvement by stethoscopic examination, in PO2 and in PCO2, suggesting that ketamine might be useful in the treatment of bronchospasm during mechanical ventilation. However, further studies are required to decide whether ketamine should be considered the drug of choice in patients with severe bronchospasm during ventilator treatment.

The purpose of the study was to review a single center's experience with the disconnect system for continuous ambulatory peritoneal dialysis (CAPD), and to evaluate peritonitis incidence with and without use of iodine-containing clamp shields. The retrospective review of patients using the disconnect system lasted from January 1991 throughout March 1993, evaluating the peritonitis incidence with and without use of iodine clamp shields. In the observation period, a total of 103 patients were evaluated. Of these, 42 patients were treated with iodine clamp shields until July 1992 and then were instructed not to use the iodine clamp shields, thus acting as their own controls. We found an overall peritonitis incidence of 0.411 episodes/patient/year (= 29.2 patient-months/episode) on disconnect CAPD-system (Baxter), in spite of the fact that more than 60% of our dialysis population is treated with peritoneal dialysis. We found no difference in peritonitis rates with or without the use of iodine clamp shields. Peritonitis rates with clamp shields were 0.400 episodes/patient/year and, without clamp shields, were 0.400 episodes/patient/year. The introduction of a disconnect system provided a system with low incidence of peritonitis. No difference in peritonitis rates was observed with or without the use of iodine clamp shields, allowing us to reduce the cost of treatment and to simplify training procedures.

Unlabelled: In this prospective study the preoperative risk classification and pulmonary status was compared to postoperative mortality and morbidity, following either spinal or general anaesthesia. We studied 408 consecutive orthopaedic patients. Comparing the anaesthetic methods we found no differences in mortality or in frequency of cardiac complications, while the non-cardiac complications were seen more frequently in patients who had undergone spinal anaesthesia (p < 0.05). Patients from the lower risk groups with a preoperative abnormal pulmonary status had a higher frequency of postoperative pulmonary complications following spinal anaesthesia than following general anaesthesia (p = 0.015)., In Conclusion: 1) We find no difference in postoperative mortality depending on the anaesthetic method chosen, 2) the predictive value of the Boston Cardiac Risk index is identical for the two anaesthetic methods, and 3) the anaesthetic method of choice for the pulmonary disabled patient has not yet been established.

Twenty-three patients subjected to arthrotomy of the knee were in a double-blind trial randomly allocated to either: 1) Indomethacin 100 mg (Confortid) administered as an enema immediately before induction of anaesthesia and repeated morning and evening for the next two days, or: b) a placebo. The patients' demand for postoperative pain treatment were registered. Survival analysis was applied to the time passed from recovery from anaesthesia until patients first asked for postoperative pain treatment. A significant difference was found (p less than 0.05). The indomethacin treated group required significantly less postoperative pain treatment than did the placebo group. 36% of the patients in the indomethacin group had no additional pain treatment during the two days of observation. Indomethacin as an enema proved to be an easy and effective way of reducing postoperative pain.

We investigated 131 consecutive patients who were submitted to orthopaedic surgical interventions under spinal anaesthesia during a period of 12 months. Prior to operation, all of the patients were classified according to the Boston Cardiac Risk Index. Immediately before operation, approximately 500 ml sodium chloride solution was infused. Patients were registered as haemodynamically unstable when a peroperative fall in the mean arterial pressure of more than 30% occurred or when the systolic blood pressure fell to less than 80 mmHg. In 40 patients, haemodynamically unstable conditions developed peroperatively while 91 were haemodynamically stable. In Boston group III, 67% of the patients were haemodynamically unstable peroperatively which was significantly more than in the Boston group I (25%) and the Boston group II (32%) (p less than 0.005). The postoperative mortality was significantly higher (13%) among the total number of peroperatively haemodynamically unstable patients than among the peroperatively stable patients (3%) (p less than 0.05). In Boston group III, the postoperative mortality was 42% as compared with 1% and 7% in the Boston groups I and II, respectively (p less than 0.05). It is concluded that the risk of fall in blood pressure during spinal anaesthesia may be predicted by the Boston Cardiac Risk Index and that patients who develop haemodynamic instability during spinal anaesthesia have an increased risk of developing complications. These patients should be offered maximal postoperative observation and care.