Use of an artificial pancreas as a tool to determine subcutaneous insulin doses in juvenile diabetes.

The present study was undertaken to examine the feasibility of determining the most appropriate subcutaneous insulin treatment in unstable diabetes on the basis of the circadian hormonal profile delivered by an artificial pancreas. The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas. The usual insulin treatment was continued to that day. Examination of the insulin pattern revealed by the artificial pancreas suggested that a valid scheme for subsequent treatment should consist of two daily injections of a mixture of short-acting and intermediate-acting insulins, which was administered to the patients beginning with the injection given after the artificial pancreas onwards. The new insulin regimen was characterized by a total daily dose that increased from 0.93 +/- 0.10 to 1.20 +/- 0.10 U/kg body weight (mean +/- SEM; P less than 0.005) as well as by a higher proportion of the dose given as regular insulin (37.1 +/- 6.9% before vs. 56.0 +/- 2.1% after; P less than 0.05). These changes led to a better control of blood glucose in 10 patients, as evidenced by a decrease of both the M value and the mean of all blood glucose levels. The mean MAGE index was not decreased, however, by the new insulin program, thereby suggesting that the lability of the disease remained unabated. These results indicate that subcutaneous treatment consisting of two daily injections of regular and intermediate-acting insulins and comprising 50 to 60% of the former could improve the metabolic control in unstable diabetes. The artifical pancreas provided a rapid and simple means to determine the appropriate doses for each type of insulin.

Differential effect of swelling and anoxia on kidney function and its consequences on the mechanism of action of intracellular organ preservation solutions.

In order to differentiate the effects of swelling and anoxia on kidney function, a canine experimental model is used. After complete liberation of kidneys and their vessels from adjacent tissues, each kidney is submitted to 10 min of hypotonic flushing, or to 60 min of normothermic anoxia. Swelling resulting from these two procedures are equal and permit the study of the consequences of anoxia independently from swelling. Edema is determined by water content and renal blood flow is measured. Kidney function is studied by time of restoration of urinary flow, creatinine, and inulin clearances and fractional water reabsorption. The results show that nonanoxic edema is much less damaging than anoxic edema and consequently that anoxic injury is not the simple consequence of spatial disruption of cell architecture. Since many works have shown the beneficial effects of intracellular organ preservation solutions and consequently that anoxia is better tolerated in the absence of swelling, it can be deduced that injuries induced by anoxia and by swelling are cumulative and that the efficiency of intracellular solutions cannot be attributed solely to the preventive effect on swelling, considered as lethal for the cell.

In vivo IgM depletion by anti-mu monoclonal antibody therapy. The role of IgM in hyperacute vascular rejection of discordant xenografts.

Xenoreactive natural antibodies (XNA) and complement activation are thought to be the 2 main factors responsible for the hyperacute vascular rejection (HVR) of discordant xenografts. The aim of this work was to study the role of IgM XNA in the HVR of guinea pig to rat cardiac xenografts, a discordant model. Adult LOU/C rats were depleted of circulating IgM and therefore of IgM XNA using an anti-mu mAb (mouse anti-rat IgM mAb 7 [MARM-7]). Rats were injected with 10 mg and 5 mg of MARM-7 at days -3 and -1, respectively, and guinea pig cardiac xenografts were performed on day 0. Control animals were injected on the same days with 10 mg and 5 mg of anti-alpha mAb (MARA-1) or equivalent volumes of PBS. Xenografts were performed on day 0. Guinea pig cardiac xenograft survival time was significantly prolonged in IgM-depleted animals (62 min, P < 0.01) compared with controls using PBS (18 min) or MARA-1 mAb (12 min). This prolongation was not due to a decrease in the complement activity in IgM-depleted rats, since no significant variation of the C1q, C4, C3, and C5 complement hemolytic activity was observed between control and treated animals before HVR. Prolongation of the xenograft survival time in the MARM-7-treated group was correlated with an undetectable serum level of IgM and IgM XNA and a lack of IgM XNA deposits on the rejected xenograft vascular endothelium. Contrarily, both IgM-depleted and control animals showed C3 deposits on the rejected xenograft vascular endothelium and myocardium, as well as diffuse deposits of IgG2a XNA. Although HVR was not abrogated by the depletion of IgM XNA, our data indicate that IgM is implicated in the HVR and that the anti-mu approach is a potential therapeutic treatment for discordant xenografts. Finally, we suggest that other factors such as IgM-independent activation of complement might be one of the mechanisms responsible for the pathogenesis of HVR in the guinea pig to rat xenograft model.

Beneficial effect of atrial natriuretic factor on ischemically injured kidneys in the rat. A new approach to improve early renal function.

In a rat experimental study we investigated whether the atrial natriuretic peptide by itself is able to improve early renal function after an ischemic injury. Two groups of Wistar male rats underwent a right nephrectomy and a left renal artery occlusion for 30 min and were infused for 2 hr after ischemia with isotonic saline or rat atrial natriuretic peptides (alpha ANF: 28 amino acids (AP 28) and atriopeptin III (AP 24): 24 amino acids). ANF infusion increased the urinary flow (P less than 0.001), the urinary sodium concentration (P less than 0.001), the sodium excretion rate (P less than 0.0001), and improved the glomerular filtration rate (GFR) recovery (P less than 0.02) determined at the end of the 2-hr infusion period. AP 24 exhibited higher natriuretics activities than AP 28. The effect of both peptides upon GFR recovery was equivalent. These effects of ANF observed after acute ischemia suggest that this peptide may be beneficial on the resumption of renal function in the early phases following transplantation.

Evidence that atrial natriuretic factor is the humoral factor by which volume loading or mannitol infusion produces an improved renal function after acute ischemia. An experimental study in dogs.

This experimental study in dogs was designed to investigate whether maximal loading produces atrial natriuretic factor (ANF) release and whether this physiological peptide is involved in the improvement of the early renal function recovery after acute ischemia. The experimental protocol included a renal artery occlusion for 45 min in uninephrectomized dogs and the measurement of various parameters of renal function over 2-hr period after declamping. There were 3 experimental groups. In the control group (I) (n = 10), the dogs received, after ischemia, an isotonic saline solution infusion at a rate of 0.2 ml/kg/min. In group II, (n = 10) the animals underwent acute volemic expansion (1 ml/kg/min) with whole blood (hematocrit approximately equal to 25%) during the ischemic period, and after declamping, an isotonic saline infusion (NaCl 0.9%) infusion at the same rate as in the control group. In group III, (n = 8) the dogs only received NaCl 0.9% (0.2 ml/kg/min) before ischemia and alpha human ANF (3.6 ng/kg/min) dissolved in saline after ischemia and during the 2 hr of the renal recovery period. Volemic expansion induced a highly significant increase of the cardiac filling pressures concomitant with a prompt but transient 5-6-fold increase in ANF levels (357 +/- 92 pg/ml versus 60 +/- 4.1 pg/ml in controls at the time of declamping [P less than 0.05]). With these higher plasma ANF levels in overloaded animals, we observed, 2 hr after declamping, considerably improved renal function recovery in terms of glomerular filtration rate--37.5% +/- 8.7 versus 11.8 +/- 3.9%; urinary sodium excretion rate--53.89 mu eq/min versus 5.36 +/- 1.2 mu eq/min (P less than 0.01); total Na reabsorption rate--1.2 +/- 0.23 meq/min versus 0.28 +/- 0.09 meq/min (P less than 0.01) (group II vs. controls, respectively). A 1-28 alpha ANF infusion after the ischemic insult allowed a comparable but more significant improved recovery of renal function--indeed, 2 hr after declamping, the GFR reached 73.7 +/- 14% of the preoperative GFR values. The urinary sodium excretion rate was 15-fold higher than in controls, and the total and fractional sodium reabsorption rates followed a similar increase. These beneficial effects of ANF were obtained with low doses of synthetic ANF (3.6 ng/kg/min) inducing plasma levels slightly higher (120 pg/ml) than in controls and comparable to the levels reached in the overloading group. In addition, maximal loading or ANF infusion produces an inhibition of the aldosterone rise occurring after the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of acute cyclosporine nephrotoxicity by atrial natriuretic factor after ischemia in the rat.

The present experimental study investigates whether the atrial natriuretic factor (ANF) is able to prevent the nephrotoxic effects of cyclosporine infused after 30 min of warm renal ischemia in the rat. At 2 hr after the end of ischemia, the glomerular filtration rate was improved by an ANF infusion: 390 +/- 19 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in ANF and saline-infused rats, respectively (P less than 0.05). Intravenous CsA infusion at a dose of 2.5 mg/kg/day produced a more pronounced fall in GFR when compared with the control: 205.4 +/- 19.7 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in CsA and saline, respectively (P less than 0.05). In contrast, a synthetic rat atriopeptin III (0.5 microgram/kg/min) infusion after ischemia given together with CsA prevented its deleterious effects upon GFR: 316 +/- 22 microliters/min/100 g versus 205.4 +/- 19 microliters/min/100 g in ANF/CsA versus CsA alone (P less than 0.001). Moreover, the natriuretic ANF effects remained unaffected by high plasma CsA peak levels: indeed, other parameters of renal function--urinary flow, urinary sodium concentration and excretion rates, and urinary sodium reabsorption and fractional excretion rates, were significantly increased in ANF alone or CsA/ANF groups. These preliminary results suggest that ANF may be useful in renal transplantation or in the management of patients given large doses of CsA (liver or heart transplant) since, despite nephrotoxic CsA levels (greater than 1500 ng/ml), ANF provides an improved GFR and tubular function after ischemia.

The unreliability of the lidocaine/monoethylglycinexylidide test for assessment of liver donors.

The serum monoethylglycinexylidide (MEGX) level 15 min (t15) after i.v. administration of lidocaine (1 mg/kg) in liver donors was retrospectively correlated with graft outcome and early hepatic function. Among the 35 orthotopic liver transplants studied, 4 recipients had to be retransplanted within 10 days post-OLT because of early graft nonfunction or dysfunction, and 3 recipients died, with a median (range) donor MEGX t15 (ng/ml) of 100 (86-119) and 169 (146-182), respectively. The remaining 28 OLT patients living with functioning grafts had a donor MEGX of 87 (18-245). No significant correlations could be found between donor MEGX t15 and recipient mean and peak glutamic-oxaloacetic and -pyruvic transaminases, total serum bilirubin, or mean and minimum prothrombin time values studied from day 1 to day 5 post-OLT. Moreover, categorization of donors using the MEGX t15 cut-off point of 80 ng/ml could not predict liver graft quality, as previously suggested. In summary, MEGX t15 in liver donors correlated neither with graft outcome nor with early functional parameters. Accordingly, the MEGX test should not be used as an isolated discriminatory evaluation for organ utilization.

Early hepatocyte, endothelial, and bile duct cell injury after pediatric liver transplantation from cadaveric or living-related donors.

BACKGROUND: When compared with cadaveric grafts (Cad), the potential advantages of pediatric orthotopic liver transplantation (OLT) from living-related (LR) donors may include better graft quality, shorter ischemic time, appropriate preparation of the recipient, and better immunologic compatibility. METHODS: The aim of this study was to analyze early hepatocyte, endothelial, and bile duct cell injury following pediatric OLT using LR (n=15) or uncomplicated Cad reduced-size (n=10) grafts. Median (range) total ischemic times were 190 min (105-261) versus 760 min (418-948) in LR and Cad groups, respectively (P<0.001). RESULTS: The post-OLT cytolytic profile, assessed daily during the first 7 days using both plasma glutamate-pyruvate transaminase and serum alpha-glutathione S-transferase, showed significantly higher levels of both parameters for the 10 uncomplicated Cad cases when compared with the 15 LR grafts (P<0.001). The evaluation of hepatic endothelial cell function during the first week after OLT, using serum hyaluronic acid levels, suggested lower endothelial injury in the LR grafts, when compared with the Cad grafts (P=0.059). Bile duct cell injury, as assessed using plasma gamma-glutamyl transferase levels, was similar in both groups, with a progressive increase at the end of the first week after OLT, which was correlated with a similar incidence of early acute rejection in both groups (80% in the LR group vs. 62% in the Cad group, NS). CONCLUSION: (1) The hepatocellular and endothelial cell damage was reduced after OLT with LR grafts, which may be related to shorter ischemic time when compared with Cad grafts; (2) the putative immunologic advantage for LR grafts was not confirmed in terms of incidence of acute rejection.

Brain tumor imaging with PET and 2-[carbon-11]thymidine.

METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated.

Preformed antibody and complement rebound after plasma exchange: analysis of immunoglobulin isotypes and effect of splenectomy.

UNLABELLED: Splenectomy (Sx) has been proposed to attenuate post-PE (plasma exchange) rebound of isoagglutinins and xenogenic (XG) antibody (Ab) in both ABO-incompatible allografts and discordant xenografts. This study analyses the qualitative nature and kinetics of serum immunoglobulins as well as complement resynthesis after PE in sham-operated (PE) and splenectomized (PE+Sx) syngeneic LOU/C rats; non-PE sham-operated or splenectomized animals were used as controls. PE was performed in unanesthetized, unheparinized rats. Immunoglobulin isotypes and subclasses (IgM, IgG1, IgG2 alpha, IgG2b) of total circulating Ab were measured pre-PE and up to 21 days post-PE, using ELISA (enzyme-linked immunosorbent assay) and specific mouse antirat monoclonal Ab. Antiguinea-pig (GP) XG Ab (IgM, IgG2a) serum levels were measured using cellular ELISA with cultured GP endothelial cells as targets. Sx alone significantly reduced XG IgM serum levels (p < 0.0001). Maximal rebound of total and XG IgM was observed on day 3 post-PE, reaching 674% and 187% of the pre-PE levels, respectively; these overshoots were entirely suppressed by Sx (p < 0.005 for total IgM; p < 0.0001 for XG IgM). Total IgG2a, IgG2b and IgG1 as well as XG IgG2a serum levels did not show significant overshoot post-PE. The activity of the complement classical pathway (mean +/- SD), assessed by CH50, was decreased at 51 +/- 19% of basal value 15 minutes after PE, and had returned to baseline level by day 2 post-PE with or without Sx. IN CONCLUSION: (1) Six alone significantly reduced XG IgM serum levels; (2) early post-PE Ab rebound was mainly observed for IgM; (3) both total and XG IgM rebound was inhibited by Sx. This suggests that Sx probably removes a significant proportion of IgM producing cells undergoing post-PE stimulation. These data provide a rationale for combining PE with Sx in ABO-incompatible and discordant XG transplantation.

[Basic data in informatics illustrated by their application in surgery]. / Quelques données de base en informatique illustrées par leur application en chirurgie.

As an introduction to a study day devoted to informatic in surgery, some basis knowledges are summarized: architecture and function of computers, programmation language, data bases. They are illustrated by various applications made in the "Cliniques St Luc" te Brussel namely patient monitoring, artificial pancreas, office system and operating room management system. The future use of local area network is proposed in order to achieve medical department independence and the needed cooperation between all users of medical and hospital informatic.

[Superselective vagotomy. Preliminary results]. / La vagotomie supersélective. Résultats préliminaires

Twelve patients suffering from an intractable duodenal ulcer are included in this review. Eleven were treated by superselective vagotomy without drainage, one had a selective vagotomy with pyloroplasty. A peroperative control of the gastric acidity after pentagastrin stimulation was used in all cases and permitted section of forgotten nerve fibers. Short-term results are satisfactory: after 2-6 months the clinical state of the patients is excellent (Visick I and II), basal acidity is decreased by 58 to 66% of preoperative value, the Hollander tests are negative except two. After more than 6 months, the few available results are satisfactory except one case of recurrent ulcer. The one case with a 1 year follow-up is excellent, clinically and as to acid secretion.

[Use of the artificial pancreas in the diagnosis and management of an insulinoma (author's transl)]. / Contribution du pancréas artificiel au diagnostic et au traitement d'un insulinome.

The artificial endocrine pancreas is generally used to control blood glucose in brittle diabetic patients. In this study, it was applied to the diagnosis and surgical management of a pancreatic insulinoma. Several tests were performed without the risks inherent to severe hypoglycemia. It was also used during surgery, permitting an optimal blood glucose control.