Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways.

Insulin and insulin-like growth factor (IGF-1) are mitogenic for fibroblasts and smooth muscle cells. IGF-1 increases in inflamed and fibrotic tissues and induces proliferation of rat hepatic stellate cells (HSC). This study evaluates the potential roles of these hormones in the development of liver fibrosis. Insulin and IGF-1 receptor expression was evaluated by immunohistochemistry in both cultured human HSC and human liver tissue. Phosphorylation of both 70-kd S6 kinase and extracellular-regulated kinase (ERK), cell proliferation, type I collagen gene expression, and accumulation in HSC culture media were evaluated by Western blot, immunohistochemistry for bromodeoxyuridine (BrdU), Northern blot, and enzyme-linked immunosorbent assay, respectively. Insulin and IGF-1 receptors were detected in HSC in vitro and in liver sections from patients with chronic active hepatitis. Insulin and IGF-1 induced 70-kd S6 kinase phosphorylation in HSC, whereas IGF-1 only induced ERK phosphorylation. Insulin and IGF-1 stimulated HSC proliferation in a dose-dependent fashion, with IGF-1 being four to five times more potent than insulin. Cell exposure to specific inhibitors showed that both phosphatidylinositol 3-kinase (PI3-K) and ERK are involved in IGF-1-induced mitogenesis, whereas insulin stimulated mitogenesis through a PI3-K-dependent ERK-independent pathway. IGF-1 increased type I collagen gene expression and accumulation in HSC culture media through a PI3-K- and ERK-dependent mechanism. In conclusion, insulin and IGF-1, which stimulate HSC mitogenesis and collagen synthesis, may act in concert to promote liver fibrosis in vivo by a differential activation of PI3-K- and ERK1-dependent pathways.

Outcome of cancer patients receiving home parenteral nutrition. Italian Society of Parenteral and Enteral Nutrition (S.I.N.P.E.).

BACKGROUND: Indication for home parenteral nutrition (HPN) in cancer patients is controversial because intestinal failure and malnutrition are often only two of the many problems found in such patients that may deserve priority of treatment. METHODS: This was a retrospective study of 75 cancer patients from nine institutions included in the Italian HPN Registry. The patients had a mean weight loss of 12.5%, serum albumin of 3.1 g/dL, lymphocyte count of 1150/mm3, and serum total iron-binding capacity of 190 micrograms/dL. The main indication for HPN was intestinal obstruction (66%); 72% of the patients had metastatic disease. A series of demographic, oncologic, and nutritional characteristics were analyzed in an attempt to predict a possible benefit of HPN. RESULTS: A total of 9897 days of HPN were delivered to 75 cancer patients, for a median of 4 months (range 1 to 15 months) per patient. Sixty-nine patients died while receiving HPN, five had a remission of their intestinal failure, and one chose to stop the treatment. Complications related to parenteral nutrition were as follows: 19 cases of sepsis, 6 catheter occlusions, 4 catheter dislocations, and 2 metabolic imbalances. HPN preserved nutritional status and slightly improved weight, lymphocyte count, serum albumin, and Karnofsky performance status in patients who survived > 3 months. Quality of life during HPN was judged by the clinicians to have improved in only 9% of those who survived < 3 months, but in 68% of the patients who survived for > 3 months. Karnofsky performance status > 50 at the start of HPN was correlated with longer survival (p = .02). CONCLUSIONS: Our study demonstrated a positive effect of HPN on nutritional status and quality of life in patients who survived > 3 months and suggests that HPN should be avoided when Karnofsky performance status is < 50.

Modifications of Intestinal Permeability Test Induced by Biliopancreatic Diversion: Preliminary Results.

BACKGROUND: Biliopancreatic Diversion (BPD), excluding the jejunum and part of the ileum from the transit of the food, reduces the absorptive intestinal area available to 250 cm of the distal ileum. The Intestinal Permeability Test (IPT) with Lactulose/Mannitol is performed to assess the intestinal mucosa function. The aim of this study was to investigate the effect of intestinal anatomical modifications induced by BPD on IPT in a group of severely obese patients. METHODS: Group A: 18 severely obese subjects who underwent BPD; the IPT was performed before (T0) and 8.2 +/- 0.9 days after BPD (T1). Group B: nine subjects of Group A; IPT was repeated 96.1 +/- 12.7 days (T2) and 180.4 +/- 19.7 days (T3) after BPD, respectively. IPT was expressed as the %Lactulose/%Mannitol ratio in the urine collected during 5 h after oral administration (normal %L/%M < 0.04). RESULTS: Data from Group A (paired Student's t-test) exhibited significantly higher values in T, with respect to T0 for %L/%M (p < 0.05) and for %L (p < 0.05), and significantly lower values in T, with respect to T0 (p < 0.001) for %M. In the Group B analysis of Variance from T0-T1-T2-T3 resulted statistically significant (p < 0.05) for % L/ % M and % M. CONCLUSIONS: The reduction of intestinal absorption surface induced by BPD causes a significant increase of the Lactulose/Mannitol IPT values, showing an intestinal mucosa function impairment. The IPT values improve progressively at 3 and 6 months after this surgical procedure.

Modifications of functional and physico-chemical properties of rat ileal plasma membranes.

A membrane fraction enriched with plasma membranes was isolated from rat ileal brush-border cells before and after five-day starvation of the animals. Cholesterol/phospholipid ratio of the standard cell membranes decreased highly significantly (0.42 to 0.18), as did the microviscosity of the membranes determined by polarization of fluorescence (0.187 to 0.142). Concomitantly, the specific activity of Na,K-ATPase in the basolateral membranes significantly increased (59 to 83 mumol ATP hydrolyzed per mg protein per min).

The influence of age and sex on nutritional parameters in subjects aged 60 years and over.

The nutritional assessment of the elderly shows several interpretative difficulties due to the lack of standard parameters. Moreover chronic age-related diseases can interfere with the physiological nutritional status. Anthropometric (triceps skinfold, arm muscle area, total body muscle mass, fat mass and Body Mass Index (BMI)), biochemical (serum prealbumin, transferrin, ceruloplasmin, total protein and albumin) and immunological (serum lymphocytes) parameters were measured in 583 out-patients aged 60 years or over selected on the basis of clinical and biochemical criteria and with BMI /= 75) for each sex. The F-test analysis for all anthropometric parameters except BMI showed significant differences with respect to age (P < 0.05) and sex (P < 0.05). Among biochemical parameters, prealbumin showed a significant difference for age (P < 0.05) and sex (P < 0.05) (males, 30.3 +/- 8.2; females, 29.1 +/- 7.5) while ceruloplasmin showed a significant difference for sex only (P < 0.05) (males, 40.9 +/- 9.3; females, 43.8 +/- 8.2). When the biochemical mean values obtained in this study were compared with those utilized in the daily routine of the hospital central laboratory, ceruloplasmin and prealbumin resulted in significantly higher (P < 0.05) while total protein and albumin were significantly lower values (P < 0.05).

A device to perform percutaneous cervical pharyngostomy (PCP) for enteral nutrition.

Percutaneous Cervical Pharyngostomy (PCP) is a technique of proven usefulness in Enteral Nutrition and has been used for over 20 years. The procedure has been modified to make it less traumatic and easier to perform. To further improve the technique we have developed a special device, with which it can be performed with minimum trauma under local anaesthesia, and with a smaller number of manoeuvres when compared with previous techniques. In addition, it gives rise to less occupation of the pharyngostomic passage by the nutritional tube (8 Fr.). We have successfully utilised this device on 37 patients, in whom the procedure took no more than 15 minutes. We had no technical complications. Based on our experience, we think that the use of this device makes the application of PCP easier in Enteral Nutrition.

[*primary osteonecrosis of the medial femoral condyle. Unicompartmental or total replacement?]. / L'ostéonécrose primitive du condyle fémoral interne. Remplacement unicompartimental ou total?

We have inserted 18 Mod II unicondylar knee replacements for idiopathic necrosis of the medial femoral condyle. The age of the patients at operation averaged 72 years, with a range of 49 to 90. The average length of follow up at review was 4 years 6 months, with a range of 2 to 8 years. The only notable complication was deterioration of the lateral compartment if operation had produced overcorrection of the tibiofemoral angle. The stability, level of pain, range of movement and function was satisfactory in 95% of the knees. The average flexion obtained was 115 degrees, and was deliberately restricted to this level to diminish stress on the lateral side. It did not result in aseptic loosening. Most knee flexion deformities were corrected at operation. Laxity and instability before operation were usually due to bone loss rather than ligament insufficiency, and were corrected by the prosthesis. A varus deformity of more than 10 degrees, a flexion deformity greater than 15 degrees or femorotibial subluxation were not considered to be contraindications to this operation.