Umbilical endometriosis associated with large umbilical hernia. Case report.

Umbilical endometriosis is a rare condition, usually following laparoscopic and surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis occurring without any previous abdominal or uterine surgery is extremely rare. The maximal depth of penetration of the umbilical endometriosis described is up to fascial level. There have been only two cases of endometriosis reported arising within umbilical hernia. The authors report a case of a patient with spontaneous umbilical endometriosis associated with a large umbilical hernia, treated by surgical excision and mesh repair of the abdominal wall. To the best of our knowledge, this is the first described case of the association of umbilical endometriosis with a large umbilical hernia that requires prosthetic mesh repair of the abdominal wall defect.

[Diabetes and research in primary care: how to improve the care of our patients?]. / Diabète et recherche en médecine de premier recours: comment améliorer la prise en charge de nos patients?

Family practitioners are well aware of the guidelines for diabetic care yet they often find it difficult to apply them in practice. Experience from the literature as well as our own research provide guidance on ways to address this problem in Primary care: 1) collaboration with a nurse practitioner for the prevention of micro and macro-angiopathic complications, 2) the use of motivational interviewing techniques to motivate patients to lifestyle changes, 3) multidisciplinary collaboration (with specialists, nurses, colleagues, pharmacists, etc) and the support of information technology. Research within the Swiss academic institutes of Primary care should provide further, more concrete, guidance on ways to apply these different options in Switzerland to improve the quality of care for diabetic patients.

Free radical modulation of insulin release in INS-1 cells exposed to alloxan.

Generation of free radicals is thought to mediate the cytotoxic action of alloxan on the pancreatic beta-cell. In this investigation, the early effects of alloxan on cell function were studied. When INS-1D insulinoma cells were exposed to alloxan (1 mM) for 45 min followed by a 3-hr recovery period, the drug increased basal insulin release while abolishing the effect of glucose in static incubations. This was associated with impaired stimulation of cellular metabolism by glucose and reduced viability, both monitored colorimetrically with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). These alterations were largely counteracted by the antioxidant butylated hydroxyanisol (BHA). Similar changes occurred when glucose was added directly after 5 min of alloxan treatment, whereas KCl-induced secretion was only partially inhibited. In perifusion, alloxan caused transient insulin secretion to 50% of the rates obtained with glucose 30 min later. Under these conditions, epinephrine abolished the stimulation due to both agents. Membrane potential and cytosolic calcium concentrations ([Ca2+]i) were recorded to clarify the action of alloxan. Alloxan-induced insulin release correlated with depolarization of INS-1D cells and a rise in [Ca2+]i. Alloxan did not augment [Ca2+]i in the presence of BHA or the absence of extracellular calcium. Nickel chloride blocked the effect of alloxan on [Ca2+]i, whereas verapamil was ineffective. This suggests that alloxan promotes Ca2+ influx through channels distinct from L-type channels, perhaps through non-selective cation channels. Thus, alloxan causes changes in INS-1D cells prevented by antioxidant treatment, suggesting that free radicals may modulate the ionic permeability leading to functional activation.

Islet autotransplantation in a cirrhotic liver.

Chronic pancreatitis resulting from alcohol abuse might in some rare cases require a total surgical resection of the pancreas to treat severe local complications. We have learned from the new techniques developed for islet isolation that it is now possible to obtain a sufficient number of good quality islets from one single pancreas to be transplanted into one recipient. We present a case of total surgical pancreatectomy for chronic pancreatitis in a previously non-diabetic patient with immediate islet isolation and autotransplantation. At operation, a cirrhotic liver was found, but no portal hypertension. We still decided to embolize a non purified preparation of endocrine tissue into the liver without alteration of liver function or durable modification of the portal pressure. One year after this procedure, the patient remains insulin-independent with a close to normal glycemic regulation as demonstrated by stimulation tests. Islet autotransplantation does not appear to be generally contra-indicated in the presence of a cirrhotic liver; provided the portal pressure is within normal limits. Under these circumstances, satisfactory glycemic control is achieved.

[The Institute of Surgery in Novi Sad as a trauma center--10 years' experience]. / Institut za hirurgiju u Novom Sadu kao trauma centar--desetogodisnje iskustvo.

UNLABELLED: Trauma is a surgical disease and a leading cause of death in the population in the age of forties. The Institute for Surgery in Novi Sad (trauma center of the first rank) takes care of all injured people brought to the Institute either directly from the place of accident or from other centers. AIM OF THE STUDY: Retrospective analysis of the injured people treated at the Institute for Surgery in the period 1987-1996. MATERIAL AND METHODS: Multivariate analysis of the traumas from the register of the Institute for Surgery according to the trauma system elements: number of injured individuals, sex and age structure, categorization of injuries, etiology of injuries, distribution of serious injuries by regions, results obtained from the treatment of serious injuries. RESULTS: They show a global representation of all elements involved with injured people: due to moderately serious, serious and critically serious injuries 21.6% of patients were hospitalized; in the age of 29-30 years men with traumas caused on work or in traffic were predominant, while women with injuries caused by falling were predominant in the age of 60-69 years; drastically increased injuries caused by fire-arms in the period 1991-1993 were directly caused by the state of war and these injuries are still numerous; in case of hospitalized patients isolated trauma (80%) was predominant, multiple trauma was under 20% and polytrauma was registered in 5% of patients; after surgical treatment of injuries approximately 17% of patients were indicated for postoperative prolonged treatment and in intensive care unit at the Institute for Surgery; the average mortality of hospitalized patients was 5-7% but with extremely high mortality rate (< 70%) in the group of patients with polytraumas.

[Android-type obesity and gynecoid-type obesity]. / Obésité de type androïde et obésité de type gynoïde.

There are several types of obesity, and the metabolic conditions associated with these phenotypes are also heterogeneous. Obesity of the male (android) type shows a dominant visceral and upper thoracic distribution of adipose tissue, whereas in the feminine (gynecoid) type adipose tissue is found predominantly in the lower part of the body (hips and thighs). Android obesity is clearly a cardiovascular risk factor, more so than gynecoid obesity. Hereditary factors contribute significantly to the occurrence of this pathology in families, although environmental factors play a role in its development. Android obesity is associated with metabolic anomalies which also characterize the syndrome X: resistance to insulin, arterial hypertension and dyslipidemia. The predisposition of individuals with android obesity to become diabetic rests in part on genetic and in part on environmental factors. Hyperinsulinemia and a high flux of free fatty acids act at the level of liver and endocrine pancreas to increase resistance to insulin and to decrease insulin secretion, two determining factors for type II diabetes. Other functional anomalies have been involved to explain android obesity such as dysregulation of adrenocortical and sexual steroids or a global derangement of stress mechanisms. No significant proof, however, seems to support either one of these hypotheses.

Improved insulin secretion of cryopreserved human islets by antioxidant treatment.

The viability of islets of Langerhans prior to grafting is believed to influence the clinical outcome of islet transplantation. To determine whether oxidative stress occurs during the isolation-purification procedure as well as during tissue culture and cryopreservation, we have measured the glutathione redox state (GSH/GSSG) of islets. Human islets were purified by standard techniques from organ donors, cultured, and cryopreserved. Glucose-induced insulin release was monitored in parallel during static incubations to assess the function of the islets. Cultured human islets responded by a 2.2-fold increase in insulin release to a glucose challenge. After cryopreservation the hormonal response was lower. Immediately after islet isolation the GSH/GSSG ratio was 25.2 +/- 5.2, and it increased slightly to 32.0 +/- 6.1 after 1-3 days in tissue culture. The GSH/GSSG decreased significantly after cryopreservation to 12.2 +/- 3.4, suggesting that the freezing and thawing procedures imposed oxidative stress on the islets. To explore this hypothesis further, cryopreserved islets were treated with the antioxidant butylated hydroxyanisole (BHA). Islets exposed to BHA showed an improved glucose-induced insulin release and had an increased insulin content. BHA also protected the islets when they were exposed to alloxan, a free radical generating agent. However, after cryopreservation, BHA treatment did not modify the glutathione redox state. Although the BHA effect could not be explained merely by a change in the glutathione redox state, it is not precluded that redox changes of other cell components ameliorate the glucose sensitivity of the beta cells. Further studies will be needed to determine possible ways of improving islet cryopreservation with antioxidant treatments and particularly, to validate the present observations by in vivo experiments in the context of clinical islet transplantation.

[Isolation and cryopreservation of human islets of Langerhans]. / Isolement et cryopréservation d'îlots de Langerhans humains.

Islet transplantation represents an alternative to whole pancreas transplantation for the treatment of patients suffering from diabetes type I. The transplantation of a sufficient number of islets is an essential condition for successful allograft. Islet cryopreservation allows the storage of islet preparations for subsequent pooling, at the time of transplantation, of cryopreserved islets with a fresh preparation in order to increase the mass of transplanted pancreatic endocrine tissue. From May 1994 to April 1995, islets were isolated from 22 human pancreases using a modified automated method, and 19 preparations were cryopreserved. The function of cryopreserved islets was tested in vitro (static incubation and perifusion). The results of static incubation experiments confirmed that the insulin secretion of cryopreserved human islets in response to glucose stimulation was comparable to the response of islets that have not been frozen. In static incubation experiments, the mean (+/- SEM) insulin secretion of islets, prior to cryopreservation, was 239.3 (+/- 58.9) and 479.5 (+/- 59.5) pg/islet/15 min at 2.8 mM glucose and 16.7 mM glucose respectively. The mean (+/- SEM) insulin secretion of cryopreserved islets was 274 (+/- 103.2) and 468.5 (+/- 191.9) pg/islet/15 min at 2.8 mM and 16.7 mM glucose respectively. The perifusion experiments also demonstrated a significant increase of insulin secretion from cryopreserved islets perifused with a stimulating glucose concentration. Our experiments allow us to envisage the use of cryopreserved islet preparations for allotransplantation in diabetic patients.

[Osteopoikilosis--case report]. / Osteopoikilosis--prikaz slucaja.

A very rare case of osteopoikilosis, a disease which is an asymptomatic, genotypical osteopathy with an unknown cause, is described. Most often it is discovered by accidental radiography and it is characterized by the appearance of spotted and oval foci of compact cortical and lameral bone inside the canselous bones. The most common localization of these disorders are epiphyses and metaphyses of the long bones. The disorders have a static character and they do not demand any kind of treatment.

Effect of 2-mercaptoethanol on glutathione levels, cystine uptake and insulin secretion in insulin-secreting cells.

The role of glutathione (GSH) in the differentiated state of insulin-secreting cells was studied using 2-mercaptoethanol as a means of varying intracellular GSH levels. 2-Mercaptoethanol (50 microM) caused a marked increase of GSH in two rat insulinoma cell lines, RINm5F and INS-1, the latter being dependent on the presence of 2-mercaptoethanol for survival in tissue culture. The effect of 2-mercaptoethanol on GSH was shared by other thiol compounds. Since in other cell types 2-mercaptoethanol is thought to act on cystine transport, thereby increasing the supply of cysteine for GSH synthesis, we have studied [35S]cystine-uptake in INS-1 cells. At equimolar concentrations to cystine, 2-mercaptoethanol caused stimulation of [35S]cystine-uptake. The effect persisted in the absence of extracellular Na+, probably suggesting the involvement of the Xc- carrier system. INS-1 cells with a high GSH level, cultured 48 h with 2-mercaptoethanol, displayed a lower cystine uptake than control cells with a low GSH content. The effect of variations of the GSH levels on short-term insulin release was studied. No alteration of glyceraldehyde-induced or KCl-induced insulin release in RINm5F cells was detected. In contrast, both in islets and in INS-1 cells, a high GSH level was associated with a slightly lower insulin release. In INS-1 cells the effect was more marked at low glucose concentrations, resulting in an improved stimulation of insulin secretion. On the other hand, in islets, a decrease in the incremental insulin release evoked by glucose was seen. As in other cell types, oxidized glutathione (GSSG) was less than 5% of total GSH, and in INS-1 cells no change in the GSH/GSSG ratio was detected during glucose-induced or 3-isobutyl-1-methylxanthine-induced insulin release. In conclusion, 2-mercaptoethanol-dependent INS-1 cells, as well as RINm5F cells and islets of Langerhans, display a low capacity in maintaining intracellular levels of GSH in tissue culture without extracellular thiol supplementation; 2-mercaptoethanol possibly acts by promoting cyst(e)ine transport; changes in GSH levels caused a moderate effect on the differentiated function of insulin-secreting cells.

Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay.

Insulin secretion depends critically on glucose metabolism. We investigated whether a rapid viability test could be established for assessing glucose metabolism in insulin secreting cells. The MTT (C,N-diphenyl-N'-4,5-dimethyl thiazol-2-yl tetrazolium bromide) colorimetric assay (reduction of tetrazolium salt to formazan) was applied to rat islets and rat insulinoma cell lines. It was found that the rate of formazan production correlated with glucose oxidation and glucose utilization at glucose concentrations which also stimulated insulin secretion. In differentiated insulinoma INS-1 cells, salt reduction paralleled the insulin release at glucose concentrations of up to 8.3 mmol/l. The glucose-induced formazan production in INS-1 cells and islets was abolished by exposure to the Beta-cell cytotoxic agents, streptozotocin or alloxan. The MTT assay thus provides a convenient tool for the rapid assessment of Beta-cell metabolism and viability.

Effects of cytokines on rat insulinoma INS-1 cells.

To investigate further the role of cytokines in the pathogenesis of type I insulin-dependent diabetes mellitus, the effects of interleukin-1 beta (IL-1), tumour necrosis factor-alpha (TNF) and gamma-interferon (IFN) were tested on rat insulinoma INS-1 cells. Whereas TNF and IFN had, respectively, a minor or no effect on insulin production, IL-1 caused a time- and dose-dependent decrease in insulin release and lowered the insulin content as well as the preproinsulin mRNA content of INS-1 cells. Both IL-1 and TNF exerted a cytostatic effect, estimated by a decrease in [3H]thymidine incorporation, while only IL-1 decreased cell viability as measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The glutathione content of INS-1 cells was shown to be modulated by the presence of 2-mercaptoethanol in the culture medium, but was not affected by IL-1 or TNF. In conclusion, INS-1 cell culture is considered to be a useful model for studying the effect of cytokines on insulin-producing cells. The differentiated features of these cells will permit several questions to be addressed regarding the mechanism of action of IL-1 and eventually other cytokines, both at the level of gene expression and of intracellular signalling.

Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines.

New insulin-secreting cell lines (INS-1 and INS-2) were established from cells isolated from an x-ray-induced rat transplantable insulinoma. The continuous growth of these cells was found to be dependent on the reducing agent 2-mercaptoethanol. Removal of this thiol compound caused a 15-fold drop in total cellular glutathione levels. These cells proliferated slowly (population doubling time about 100 h) and, in general, showed morphological characteristics typical of native beta-cells. Most cells stained positive for insulin and did not react with antibodies against the other islet hormones. The content of immunoreactive insulin was about 8 micrograms/10(6) cells, corresponding to 20% of the native beta-cell content. These cells synthesized both proinsulin I and II and displayed conversion rates of the two precursor hormones similar to those observed in rat islets. However, glucose failed to stimulate the rate of proinsulin biosynthesis. In static incubations, glucose stimulated insulin secretion from floating cell clusters or from attached cells. Under perifusion conditions, 10 mM but not 1 mM glucose enhanced secretion 2.2-fold. In the presence of forskolin and 3-isobutyl-1-methylxanthine, increase of glucose concentration from 2.8-20 mM caused a 4-fold enhancement of the rate of secretion. Glucose also depolarized INS-1 cells and raised the concentration of cytosolic Ca2+. This suggests that glucose is still capable of eliciting part of the ionic events at the plasma membrane, which leads to insulin secretion. The structural and functional characteristics of INS-1 cells remained unchanged over a period of 2 yr (about 80 passages). Although INS-2 cells have not been fully characterized, their insulin content was similar to that of INS-1 cells and they also remain partially sensitive to glucose as a secretagogue. INS-1 cells retain beta-cell surface antigens, as revealed by reactivity with the antigangloside monoclonal antibodies R2D6 and A2B5. These findings indicate that INS-1 cells have remained stable and retain a high degree of differentiation which should make them a suitable model for studying various aspects of beta-cell function.

[Injuries in Vojvodina 1989]. / Prikaz traumatizma u Vojvodini 1989.

Trauma has all sociomedical characteristics and importance which line up it in the leading problems of the contemporary medical pathology. Injuries are among the first five groups of the diseases in the structure of overall outpatient's morbidity (general medicine 4.05%, occupational medicine 7.57%, pediatric medicine, 1.84% and health service for pupils 4.96%) and are a significant cause of hospitalization. Concerning the very thorough and all-inclusive follow up of all aspects of trauma it is necessary to establish the regional register of injury and intoxication.

[Early functional and anatomic results after total condylar knee prosthesis implantation]. / Rani funkcionalni i anatomski rezultati nakon ugradnje totalne kondilarne endoproteze kolena.

The results of total knee replacement in 30 patients have been analyzed. Total knees were implanted during 1990, and the shortest follow-up time after the operations amounted to 6 months. All 30 total condylar prosthesis were of Insall-Burstein posterior stabilized design. The average age of the operated patients was 61 years. Osteoarthritis caused serious knee damage in 21 patients and was the indication for the operation; in 7 patients it was rheumatoid arthritis; in 1 patient synovitis villonodularis; and severe posttraumatic osteoarthrosis in 1 patient. In 18 patients axial knee deformity was noted prior to operation in the sense of valgus or varus. The continuous passive motion machine was used in the postoperative treatment of all patients. Clinically acceptable results were obtained in 90%. Wound healing complications were noted in 2 patients. Full axial deformity correction was achieved in all the patients with a full extension and flexion of over 90 degrees in the operated knees. Preliminary results after the implantation of this type of prosthesis are very encouraging and justify it's further routine use.

[Incorporation of nonvascularized auto- and allotransplanted bone into the site of bone defects]. / Inkorporacija nevaskularizovanih kostanih auto i alotransplantata na mesto kostanog defekta.

It is generally accepted viewpoint that free bone grafts do not survive transplantation, that the incorporation of the autograft is faster and safer than the one of the allograft, and that the immunological processes disturb the process of revascularisation and reossification of the graft, although they stimulate the process of absorbtion. The process of graft incorporation into the host's bone was followed up in 8 dogs, i.e. 16 knees. In 10 knees the medial tibial condyle was replaced by autogenic implants made of patella, thickness of 6-8 mm. and fixed by Kirschner wire. The process of allograft incorporation was studied in 6 knees, where the medial tibial condyle was replaced by the donor's graft. The process of the graft incorporation was followed-up by x-ray studies and after sacrificing the animals during the interval starting from 2 months to a year since the operation had been performed, while in the allograft group the follow-up was during the interval starting from 1 up to 5 months. The obtained results point out that the incorporation of the bone grafts thinner that 1 cm happens within first 8-10 months after the operation. The process of incorporation during this period happens at almost the same speed in both groups. If there are no technical errors while implanting, practically all the grafts of this thickness will be incorporated into the host's bone, i.e. completely reosified and revascularized. The congruity of the joint and the rigidity of the fixation play the main role in the fate of the graft within the first months after the operation.

[Degenerative arthritis of the knee joint after allotransplantation of the joint surface without immunosuppression]. / Degenerativni artritis kolenog zgloba nakon alotransplantacije zglobne povrsine bez primene imunosupresije.

Degenerative arthritis of the knee joint after resurfacing of the knee with fresh osteochondral allograft occurs frequently and was noticed a long time ago. The main causes can be: incongruity of the joint, when the allograft slips so that its surface is out of normal line, inadequate internal fixation different methods of cartilage preservation which are lethal to cartilage, broken grafts as well as immunological reaction to the graft. The experiment was conducted on 5 dogs, i.e. 10 knees. As for operated knees, the medial tibial condyle was replaced by fresh osteochondral allograft taken from the other animal, without preservation, performing precise operative technique and rigid internal fixation. These allografts were followed-up by x-raying them and after sacrifying the animals. The following-up of the development of the degenerative process continued up to 6 months after transplantation. The obtained results point out all the attitudes concerning all the other arthroplastic procedures (such as the precise reconstruction of the joint surface and the rigid internal fixation) should be respected. In spite of this, degenerative arthritis still exists in some cases as the result of immunological reaction to the graft, the process which may start within 6 months after transplantation.

Sodium requirement for insulin release: putative role in regulation of intracellular pH.

The effects on insulin release of Na+ removal, alteration of extracellular pH, and inhibition of acid extrusion processes were examined using freshly isolated and 46-h cultured islets of Langerhans. Na+ removal inhibited the secretory response to 16.7 mM glucose specifically in fresh islets but stimulated the low-glucose response in cultured islets. These divergent effects of Na+ depletion were perfectly mimicked by amiloride, an inhibitor of Na+-H+ exchange, and could be overcome in a raised HCO-3, pH 8.0 medium. Simply raising extracellular pH at constant HCO-3 had no effect. Na+ removal also inhibited the secretory responses to other nutrient secretagogues such as D-glyceraldehyde and L-leucine but not to agents like 3-isobutyl-1-methylxanthine or 12-O-tetradecanoylphorbol-13-acetate. The results show that Na+ is not itself essential for the secretory process but rather suggest that it plays a permissive role in the regulation of intracellular pH via Na+-H+ exchange. Such a regulation appears important mainly for nutrient-stimulated insulin release, which is associated with the generation of acidic metabolites.