Can the kidney function as a lung? Systemic oxygenation and renal preservation during retrograde perfusion of the ischaemic kidney in rabbits

OBJECTIVE: To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS: After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS: The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION: Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.     

Prenatal diagnosis of triploidy

Triploidy is one of the most common chromosomal numerical aberrations, resulting usually from one out off two main mechanisms: aberrant segregation of chromosomes during meiosis or from the fertilization of one egg by two sperms. In present paper the methods of non-invasive and invasive prenatal diagnosis of triploidy in I and II trimester are described. We also report the case of triploid fetus, diagnosed by ultrasound visualisation followed by amniocenthesis and cytogenetic analysis.     

Weitere Erfahrungen mit dem Äquatorimpressionsglas

Zusammenfassung Wir berichteten vor kurzem über das Äquatorimpressionsglas; man kann damit die Fundusperipherie zwischen Äquator und Ora serrata nicht nur nasal und temporal, sondern auch oben und unten ohne Schwierigkeiten binocular an der Spaltlampe untersuchen. Bei der Untersuchung mit den Impressionskontaktgläsern (Oraglas nach Goldmann und Schmidt und Äquatorimpressionsglas) sollen Binocularmikroskop und Lichtspalt auf die Gipfelzone der Fundusimpression eingestellt werden. Man untersucht daher die Zone zwischen Äquator und Ora serrata mit dem Äquatorimpressionsglas. Ora serrata und Pars plana dagegen mit dem Oraglas.

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Summary We recently reported about the equator-impression-glass. With this instrument it is possible to do a binocular examination of the periphery of the fundus between equator and ora serrata at the slit-lamp without any difficulty not only nasally and temporally but also above and below. During the examination with the impression-contact-glasses (ora-glass after Goldmann and Schmidt and equator-impression-glass) binocular microscope and light slit should be focused upon the summit zone of the fundus impression. Therefore, we examine the zone between equator and ora serrata with the equator-impression-glass, ora serrata and pars plana, in the contrary, with the ora-glass.

     

Spaltlampenphotographie der Netzhautrandzone und Pars plana des Ciliarkörpers

Zusammenfassung Es werden die technischen Einzelheiten der in der vorangehenden Arbeit beschriebenen Methode der Spaltlampenphotographie der Netzhautrandzone und Pars plana des Ciliarkörpers erläutert. Besonders durch stereoskopische Aufnahmen gelingt es, die Anschaulichkeit der visuellen Betrachtung, wie sie beim Untersuchen an der Spaltlampe mit Impressionskontaktgläsern besteht, annähernd zu erreichen.

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Slitlamp photography of the extreme fundus periphery, ora serrata and pars plana of the ciliary bodyII. Technical details

Summary The method of slit-lamp photography of the ora serrata and the pars plana of the ciliary body was described in the previous paper. Now the technical details are explained. Stereoscopic photographs give almost the same visual impression as examination with the slit-lamp with depression contact glasses.

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Auszugsweise vorgetragen in der 15. Jahreshauptversammlung der Österreichischen Ophthalmologischen Gesellschaft 1.–4. Juni 1972 in Baden bei Wien.     

Early onset of proteinuria and focal segmental glomerulosclerosis in obese,hyperinsulinemic adolescents developing metabolic syndrome

BackgroundThe metabolic syndrome (MTS) is comprised of insulin resistance, glucose intolerance, obesity, hypertension, and dyslipidemia. Secondary renal dysfunction can develop after prolonged duration of each component except for dyslipidemia. Here we present 7 obese individuals in whom MTS and proteinuria developed concomitantly during adolescence.Subject and methodsSeven (f:m = 4:3) individuals (Caucasian or African American, ages 11–17 at disease onset) developed macroproteinuria of whom 6 were directly evaluated and had typical MTS characteristics. Body mass index range was 30.8–73.2 kg/m², being highest in African Americans. All had positive family history of MTS. Six patients underwent complete general, hormonal and metabolic work-up, including fasting and stimulated insulin and C-peptide levels. Genomic DNA of 4 patients and their relatives was studied by linkage analysis for MODY 1–4 genes, and for a locus associated with focal segmental glomerulosclerosis (FSGS) and microalbuminuria.ResultsFasting and stimulated insulin and C-peptide levels were elevated. All patients were normoalbuminemic, and five of six patients had mildly elevated liver enzymes. The 24-h urinary protein excretion range was 2.5–9 g, and decreased markedly in 2 patients who lost weight. Renal biopsy of 3 patients showed FSGS. In 2 pedigrees FSGS was familial. Genomic DNA analysis excluded any linkage with common MODY genes or with familial FSGS.ConclusionsThe early concomitant development of MTS, proteinuria and FSGS appears to be associated with hyperinsulinemia, presenting as early as adolescence, and may be reversed by weight loss. We propose that in genetically predisposed individuals, excessive insulin plays a crucial pathogenic role in development of the metabolic syndrome and FSGS.     

Correlations between measures of insulin sensitivity and weight loss

OBJECTIVE: Many formulas have been proposed to calculate insulin sensitivity and studies have shown their effectiveness. However, few studies have been done to compare formulas. METHODS: Seventy-two obese participants completed a randomized weight loss study. Weight loss, change in body fat and change in waist circumference were used as surrogates for change in insulin sensitivity. Correlation coefficients were calculated for each of these surrogates with proposed formulas for insulin sensitivity found in the literature. RESULTS: The change in insulin sensitivity using the formula proposed by McAuley (exp(2.63-0.28 x ln(fasting insulin)-0.31 x ln(fasting triglyceride in mmol/l)) showed the greatest correlation with weight loss (r=-0.59, p<0.0001) and was statistically superior to change in fasting glucose, fasting insulin and homeostasis model assessment (HOMA). CONCLUSIONS: The insulin sensitivity formula proposed by McAuley provides an accurate means of detecting insulin resistance. As it does not require a glucose tolerance test, it is also easier and less expensive than most other formulas. Use of this formula rather than fasting glucose would detect many more patients with insulin resistance who are at risk for subsequent diabetes and other complications.     

Gravity-osmotic pressure effect for flat polymeric membranes and three-component non-electrolyte solutions

In this paper the classification of the gravitational effects in a passive transmembrane transport is presented. Among these effects there are the flux (flux graviosmotic effect, flux gravidiffusive, current gravielectric effect) and force (pressure graviosmotic effect, pressure gravidiffusive effect, voltage gravielectric effect) gravitational effects. The pressure graviosmotic effect model equation in a single-membrane system is elaborated. In this system the flat, microporous and symmetric polymeric membrane (Nephrophan) positioned horizontally separated water and binary (aqueous glucose) or ternary (glucose-0.2 mole/l) aqueous ethanol) non-electrolyte solutions. The calculations of pressure graviosmotic effects for two (A and B) configurations of the single-membrane system were elaborated. In configuration A solution was placed in compartment below membrane and in configuration B--above membrane. These calculated results are interpreted in terms of the convective instability that increases the diffusive permeability coefficient of complex: boundary layer/membrane/boundary layer.     

Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity

To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1–associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%–60% lower following the lipid infusion compared with the glycerol infusion and were associated with a ~90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1–associated PI 3-kinase activity.     

Oxidative stress in female B6C3F1 mice following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Hassoun et al. (1998, Toxicol. Sci. 42, 23-27) reported an increase in the production of reactive oxygen species (ROS) in the brain of female B6C3F1 mice following subchronic exposure to TCDD at doses as low as 0.45 ng/kg/day. In the present study, oxidative stress was characterized in liver, spleen, lung, and kidney following subchronic (0.15-150 ng/kg; 5 days/week for 13 weeks, po) or acute exposure (0.001-100 microg/kg, po) to TCDD in order to investigate the interaction between tissue concentration and time for production of ROS. Seven days following acute administration of TCDD, mice were sacrificed; they demonstrated increases in liver superoxide anion production (SOAP) and thiobarbituric acid reactive substances (TBARS) at doses of 10 and 100 microg/kg, associated with hepatic TCDD concentrations of 55 and 321 ng/g, respectively. Liver obtained from mice following subchronic TCDD exposure demonstrated an increase in SOAP and TBARS above controls at doses of 150 ng/kg/day with liver TCDD concentration of only 12 ng/g. Interestingly, glutathione (GSH) levels in lung and kidney following sub-chronic TCDD exposure were decreased at the low dose of 0.15 ng/kg/day. This effect disappeared at higher TCDD doses. The data suggest that higher tissue TCDD concentrations are required to elicit oxidative stress following acute dosing than with subchronic TCDD exposure. Therefore, the mechanism of ROS production following TCDD exposure does not appear to be solely dependent upon the concentration of TCDD within the tissue. In addition, very low doses of TCDD that result in tissue concentrations similar to the background levels found in the human population produced an effect on an oxidative stress endogenous defense system. The role of this effect in TCDD-mediated toxicity is not known and warrants further investigation.