Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

BACKGROUND/OBJECTIVES: Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. SUBJECTS/METHODS: The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). RESULTS: Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. CONCLUSIONS: Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate.

BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. RESULTS: GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. CONCLUSION: In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP.

The macrophage activation marker sCD163 is associated with changes in NAFLD and metabolic profile during lifestyle intervention in obese children.

BACKGROUND: Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s)CD163 is a macrophage activation marker. OBJECTIVES: To associate sCD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention. METHODS: We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography. RESULTS: Baseline sCD163 was higher in children with elevated alanine transaminase (ALT) (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.03), steatosis (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.01) and high paediatric NAFLD fibrosis index (2.3 ± 0.7 vs. 1.9 ± 0.6 mg L(-1) , P = 0.03). Baseline sCD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol. CONCLUSION: sCD163 was associated with markers of liver injury and metabolic parameters in obese children, and changes in these parameters during lifestyle intervention. This may suggest that activated macrophages play a role in NAFLD and sCD163 may serve as a marker of liver disease severity and treatment effect.

Intra-aortic balloon pumping increases renal blood flow in patients with low left ventricular ejection fraction.

Intra-aortic balloon pumping (IABP) has, for decades, been one of the key treatment modalities following impaired cardiac function after cardiac surgery. IABP increases cardiac output, decreases oxygen consumption of the heart and relieves the left ventricle. However, a number of complications have been reported in connection with IABP treatment. Only a few studies have evaluated renal blood flow and the purpose of this prospective study was to evaluate whether renal blood flow was affected by IABP treatment in high-risk patients. After approval from the county ethical committee and informed consent, seven consecutive patients with low left ventricular ejection fraction and scheduled for preoperative IABP treatment were allocated to the study. Assessment of renal blood flow was based on ultrasound spectral Doppler estimation of the flow velocity profiles in the interlobar kidney arteries. The result was described as balloon index (BI), which is maximal systolic velocity divided by the temporal mean velocity. Typical velocity profiles were demonstrated in all patients before, during and after IABP. BI measurement changed with time (p <0.05). BI was lower during IABP compared to both pre-IABP and post-IABP (p <0.025), indicating a higher renal blood flow. No statistically significant changes were seen in s-creatinine or creatinine clearance. Assuming unchanged diameter of kidney arteries and no considerable decrease in renal resistance and/or compliance, we conclude that the interlobar renal blood flow was significantly increased during IABP treatment, measured by ultrasound Doppler technique, but without a simultaneously significant change in creatinine clearance.

The effect of TNFalpha blockade in complicated, refractory Kawasaki disease.

In Kawasaki disease (KD), a systemic vasculitis of childhood, serum levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) are elevated during the acute phase of the disease. Although the majority of children recover completely from a single dose of intravenous immunoglobulin (IVIG), the treatment is not always effective. In refractory cases of KD there are no documented treatment guidelines. A future role of biological agents directed against proinflammatory cytokines has recently been suggested by the American Heart Association (AHA). We describe two infants with severe KD, complicated by coronary as well as extracoronary aneurysms, who responded neither to repeated treatment with IVIG plus aspirin nor to corticosteroids. The children were subsequently treated with infliximab. In both cases, the effect was prompt and long-lasting. Clinical improvement was seen within a few days after the first dose, and regression of the aneurysms occurred within weeks.

Changes in renal dimensions evaluated by magnetic resonance imaging and ultrasonography during long-term ciclosporin-A treatment.

PURPOSE: To investigate changes in renal dimensions during long-term treatment with ciclosporin-A (CsA). MATERIAL AND METHODS: Five mini-Göttingen pigs were treated with CsA (10 mg kg(-1) day(-1)) for 6 months; 3 untreated animals served as controls. Renal length was measured by magnetic resonance imaging (MRI) and ultrasonography (US); renal volume by MRI. Examinations were performed at baseline (0 weeks) and after the start of CsA treatment at intervals of 5 weeks (5-25 weeks). RESULTS: Comparison of baseline and end-point data (0 weeks vs. 25 weeks) revealed a statistically significant increase in renal volume in CsA-treated animals (87.1 cm3 vs. 55.9 cm3, P=0.002). Renal volume remained unchanged in the control group. A significant increase in renal length was found both in the CsA-treated pigs (MRI: 96 mm vs. 84 mm, P<0.001; US: 94 mm vs. 81 mm, P<0.001) and in the control group (MRI: 97 mm vs. 85 mm, P<0.001; US: 89 mm vs. 81 mm, P=0.018). No difference was found between MRI and US measurements based on 40 paired units (MRI variance: 2.4-30.3% and US variance: -5.1-40.6%, P=0.133). CONCLUSION: During long-term CsA treatment, renal volume increases in mini-pigs, but there is no correlation between the increase in volume and the increase in length in this pig model.

Chronic cyclosporine nephrotoxicity: a pig model.

Cyclosporine A (CsA) is one of the keystones in immunosuppressive treatment after solid organ transplantation, despite its major side effects such as nephrotoxicity. The chronic nephrotoxic effects of CsA seen in humans have been difficult to reproduce in small-animal models. The aim of the present study was to examine the chronic nephrotoxicity produced by therapeutic dosages of CsA in a pig model. Among 11 Gottingen minipigs included in the study, three died, yielding data from five animals given CsA (10 mg/kg/d, orally) for 6 months, and three controls. Body weight, blood pressure, glomerular filtration rate (GFR) by plasma clearance of (51)Cr-ethylenediamine-tetraacetic acid, CsA concentration, serum creatinine, and other values were measured every 5 weeks. Our results showed that the whole blood trough CsA levels were lower in pigs than in humans treated with similar CsA doses. Renal biopsies, which were obtained successfully, except one case of macroscopic hematuria, showed no histological changes in the kidney. No significant increase in serum creatinine or blood pressure was observed. Surprisingly, there was a significant increase in GFR during CsA treatment. We conclude that the pig model displays a hyperfiltration that warrants further investigation.

Resistive index: an experimental study of the effects of diuretic stimulation in the unobstructed porcine kidney.

OBJECTIVE: To study the effects of diuretic stimulation with frusemide and mannitol on the renal resistive index (RI) of the undilated unobstructed porcine kidney. MATERIALS AND METHODS: Experiments were carried out on 14 pigs divided into two equal groups (A and B), under general anaesthesia. In all pigs both ureters were catheterized, thereby allowing urine output to be measured on each side separately, and an indwelling catheter in a femoral artery used to continuously measure the systemic blood pressure. Furthermore, in five pigs from each group, right renal blood flow was measured by ultrasonic flow probes placed around the renal arteries. The right kidney RI was measured at baseline and at 5-min intervals after frusemide (group A) and mannitol (group B) stimulation, for 75 min. RESULTS: Frusemide caused significant increases in diuresis (P < 0.001) and renal blood flow (P = 0.009). This was accompanied by a significant decrease in mean arterial pressure (P < 0.001). The RI was unaffected (P = 0.706), with mean values in group A of 0.58-0.65. Mannitol also caused a significant increase in diuresis (P < 0.001) and a subtle but significant decrease in mean arterial pressure (P < 0.001). However, renal blood flow was unaffected by the diuretic (P = 0.820); the mean RI values were unaffected, at 0.61-0.66 (P = 0.375). CONCLUSIONS: These results show that diuretic stimulation with frusemide or mannitol does not affect the RI of the unobstructed undilated porcine kidney, despite significant changes in diuresis, renal blood flow and mean arterial pressure.

Short- and long-term repeatability of intrarenal resistive index in the pig.

RATIONALE AND OBJECTIVES: To evaluate the short- and long-term repeatability (intraobserver variation) of the renal resistive index (RI) in a pig model. METHODS: Under standardized ambient conditions, short- and long-term repeatabilities were assessed by measuring the RI three consecutive times at 30-minute intervals in 14 pigs and twice 4 weeks apart in 6 pigs, respectively. Repeatability was judged according to predefined criteria, which included calculation of coefficients of variation (CVs) and repeatability coefficients combined with visual assessment and estimation of bias. RESULTS: Short-term repeatability was acceptable, having an average CV of 4.9% +/- 2.9% and of 6.1% +/- 4.7% in two comparisons, findings that were reiterated in the visual assessment. Long-term results were, however, less consistent, having an average CV of 8.1% +/- 6.1% and prominent scatter on the visual assessment graphs. CONCLUSIONS: In this study, RI measurements showed an acceptable short-term repeatability, whereas long-term results were less consistent. The components of error contributing to the modest long-term repeatability need to be investigated in studies of larger populations.

The intrarenal resistive index as a pathophysiological marker of obstructive uropathy.

PURPOSE: The intrarenal resistive index is a physiological parameter that indirectly reflects the degree of resistance in the intrarenal vasculature. Resistive index measurements have been advocated for the diagnostic evaluation of several renal pathologies, including obstructive uropathy. However, despite extensive research in this field during the last decade clear guidelines on the use of resistive index measurements for discriminating obstructive from nonobstructive dilatation of the upper urinary tract remain elusive. Therefore, we reviewed the literature to clarify the proper role of resistive index measurements in the context of obstructive uropathy. MATERIALS AND METHODS: We reviewed the recent literature on the use of resistive index measurements for the diagnostic evaluation of obstructive uropathy. RESULTS: Despite a continuously growing body of literature the resistive index has yet to be recognized as a dependable parameter when it comes to resolving the long-standing dilemma of the dilated upper urinary tract. While proponents have observed that this method has sensitivity and specificity that supersede those of conventional methods, opponents have reported that the resistive index is an unreliable parameter that is prone to systemic and local influences. CONCLUSIONS: Resistive index measurements are still in a developmental phase. Additional studies are needed before this technique may be used reliably for the diagnosis of obstructive uropathy.

Resistive index: an experimental study of the normal range in the pig.

OBJECTIVES: To study the normal range and distribution of the resistive index (RI) and the resistive index ratio (RIR) in the non-obstructed non-dilated porcine kidney, and to assess the reliability of the threshold values RI 0.70 and RIR 1.10 as prognosticators of true obstruction in the upper urinary tracts. METHODS AND MATERIALS: Twenty female pigs of Danish land race breed were studied under general anaesthesia. Blood pressure and urine output was monitored throughout the experiment. Doppler evaluations were obtained from an interlobar artery in the lower half of each kidney, and the RI was calculated as the average of 3 x 3 cycles for each side independently. Statistical analysis of the obtained results was performed. RESULTS: Forty renal units were studied. The RI values ranged from 0.48-0.85 (mean 0.63). Nine renal units (22.5%) had RI values > or = 0.70. RIR values ranged from 1.00-1.38 (mean 1.07). Three RIR values (15%) were above 1.10. There was no statistically significant relationship between RI and laterality (p = 0.25), and no overall significant relationship between RI and mean arterial blood pressure (r2 = 0.21) or urine output (r2 = 0.004). CONCLUSIONS: This study shows a wide distribution of the RI normal values in the pig model, and our results do not support the normal ranges for RI and RIR, or the cut-off values used in clinical practice.

The possible role of ultrasound in early cervical cancer.

The value of preoperative ultrasonography to detect lymph node metastases in patients with early cervical carcinoma (stage IB-IIA) was investigated in 111 patients. Comparison was made between ultrasound and the operative histopathologic findings in 109 patients and with fine-needle biopsy in 2 patients. The positive predictive value was 71%, and the negative predictive value was 84%. Sensitivity was 23%, specificity was 98%. Lymph node metastases were found in 19% (21 patients) by operative histopathologic examination; these patients received subsequent radiotherapy. The rest, 92 patients with no lymph node metastases at Meigs' operation, were followed by abdominal and transvaginal ultrasonography as well as clinical examination at 6, 9, 12, 18, 24, 36, and 48 months postoperatively to detect recurrences. The recurrence rate was 9.8%. Ultrasound alone detected only one recurrence in an asymptomatic patient. We conclude that ultrasonography is not reliable in the preoperative detection of lymph node metastases. Moreover, ultrasound examination presents no advantage over clinical examination in early detection of asymptomatic recurrent cervical cancer after radical hysterectomy.

The value of bone marrow examination in small cell carcinoma of the lung.

Of 668 consecutive patients with SCLC, 472 underwent bone marrow examination for staging. In 330 patients a triple examination (sternal aspiration, iliac crest aspiration and biopsy) was performed, otherwise a single procedure. Bone marrow infiltration (MI) was found in 37% of the patients with extensive disease, and the frequencies of a positive finding in single and triple examination were not statistically different. In the group having triple examination performed iliac crest aspiration alone disclosed MI in 32%. When all three procedures were included still more patients with MI were found (42%) but the two values were not significantly different. In 6.6% of patients who would have been classified as 'limited' did bone marrow examination change the stage to extensive disease. Based on these results we recommend iliac crest aspiration, but not triple examination with iliac crest biopsy, in the staging of SCLC.

[Residual metastases from testicular cancer. CT as a diagnostic and strategic adjuvant]. / Restmetastaser fra cancer testis. CT som diagnostisk og strategisk adjuvans.

Forty-nine young males with advanced testicular cancer treated between March 1982 and June 1989 comprised a 49/588 (8%) subgroup with distant metastases to the retroperitoneum, mediastinum and lungs, and required mandatory surgery on basis of the risk for reactivation of "slumbering" malignant components in tumor tissue temporarily inactivated by chemotherapy and/or radiotherapy. Preoperative CAT-scan was carried out with the intention of mapping regional pathology related to the size, number, burden of the tumor tissue, and the occasional and prognostic ominous invasion of the great vessels. Regarding radical surgery, the positive predictive value of CAT-scan was found to be 33/34 (97%). The negative predictive value was 5/15 (33%) and was interpreted as an expression of the radiologist's cautious assessment. 14/49 (29%) died before March 1990. Poor prognosis was related to invasion of major vessels and was found in 14 patients of whom eight died. It seems established that CAT-scan presents an extremely valuable preoperative investigation when it comes to planning of surgical strategy in a patient population with testicular cancer metastases with difficult access.

The cortical distribution pattern of diabetic glomerulopathy.

In advanced diabetic nephropathy, all nephrons are affected. However, glomerulopathy shows some variation in severity. The aim of this study was to see whether the distribution of glomerular lesions bears any relationship to known renal anatomical/functional organization. Autopsy material from 12 long-term Type 1 (insulin-dependent) diabetic patients was collected retrospectively. Sections presenting the whole depth of cortex were subdivided into 3 zones of equal width. Two parameters were estimated in the deep and the superficial zones separately: in open glomeruli, the volume of red-stained (PAS-positive) material as a fraction of the total glomerular volume, and the number of occluded glomeruli as a fraction of the total number. The results show that the volume fraction of red-stained (PAS-positive) material, as well as the frequency of occluded glomeruli, are similar in the superficial and the deep zone. In addition, the spatial distribution of occluded glomeruli was tested for randomness. The occluded glomeruli are not randomly distributed, but show clustering. Furthermore, they tend to be located in columns perpendicular to the kidney surface, a tendency which cannot be explained by the general tendency for glomeruli to show such an arrangement. We conclude that it is unlikely that the combined structural and functional differences that exist between the superficial and deep glomeruli play a major role in the development of diabetic glomerulopathy. The kidney topology influences the process of glomerular occlusion. Several a priori, plausible mechanisms for the process are discussed.

Diabetic glomerulopathy. Structural characteristics of the early and advanced stages.

Studies of the glomerular structure in diabetes mellitus have helped to elucidate the basis for some functional abnormalities. The decline in glomerular filtration occurring in many long-term diabetics is a functional disorder of great clinical importance. Quantitative structural studies of the glomeruli in diabetics at different stages of disease are necessary to learn about the development of structural changes leading to the end-stage kidney disease. Preliminary results of a study of glomeruli from long-term diabetics with clinical nephropathy are compared with those obtained in control subjects and in diabetics within the first 5 yr of disease. In the long-term diabetics the peripheral basement membrane thickness was doubled. On the average, mesangial regions occupied nearly 60% of the total tuft volume as compared with 33% in the early stages. A marked accumulation of basement membrane material in the mesengial regions had taken place so that 85% of the total basement membrane material of the tufts (i.e., peripheral basement membrane in the capillary walls plus mesangial basement membrane-like material) was localized within the mesangial regions. In the early stages equal amounts were found at these two different sites. The distribution of the lesions within the kidney is under investigation in a light microscopic study of autopsy material from long-term diabetics with varying degrees of glomerulopathy. The severity of the diabetic glomerulopathy was quantitated separately within the superficial and the deep cortical zones. The results showed that there was no tendency toward increased severity in the deep glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)