Pullout strength of tibial graft fixation in anterior cruciate ligament replacement with a patellar tendon graft: interference screw versus staple fixation in human knees

The endoscopic single incision technique for anterior cruciate ligament (ACL) reconstruction with a femoral half-tunnel may lead to a graft/tunnel mismatch and subsequent protrusion of the block from the tibial tunnel. The typical tibial fixation with an interference screw is not possible in these cases. Fixation with staples in a bony groove inferior to the tunnel outlet can be used as an alternative technique. Current literature does not provide biomechanical data of either fixation technique in a human model. This study was performed to evaluate the primary biomechanical parameters of this technique compared with a standard interference screw fixation of the block. Fifty-five fresh-frozen relatively young (mean age 44 years) human cadaver knee joints were used. Grafts were harvested from the patellar tendon midportion with bone blocks of 25 mm length and 9 mm width. A 10-mm tibial tunnel was drilled from the anteromedial cortex to the center of the tibial insertion of the ACL. Three different sizes of interference screws (7 × 30, 9 × 20, 9 × 30 mm) were chosen as a standard control procedure (n = 40). For tibial bone-block fixation the graft was placed through the tunnel, and the screw was then inserted on the cancellous or the cortical surface, respectively. Fifteen knees were treated by staple fixation. A groove was created inferior to the tunnel outlet with a chisel. The bone block was fixed in this groove with two barbed stainless steel staples. Tensile testing in both groups was carried out under an axial load parallel to the tibial tunnel in a Zwick testing machine with a velocity of 1 mm/s. Dislocation of the graft and stiffness were calculated at 175 N load. Maximum load to failure using interference screws varied between 506 and 758 N. Load to failure using staples was 588 N. Dislocation of the graft ranged between 3.8 and 4.7 mm for interference screw fixation and was 4.7 mm for staples. Stiffness calculated at 175 N load was significantly higher in staple fixation. With either fixation technique, the recorded failure loads were sufficient to withstand the graft loads which are to be expected during the rehabilitation period. Staple fixation of the bone block outside of the tunnel resulted in a fixation strength comparable to interference screw fixation. Received: 2 September 1996 Accepted: 30 January 1997     

Gene transfer to the patellar tendon

Growth factors have the potential to enhance native repair responses in ligamentous lesions. However, methods for applying these cytokines to sites of injury for extended periods are lacking. We suggest that local transfer of genes which encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study, the retroviral vectors MFG lacZ and BAG lacZ neo^r and adenovirus LacZ were evaluated for their ability to deliver genes to cells of ligamentous origin. The posterior and anterior cruciate ligaments, medial collateral ligament, semitendinosus tendon and patellar tendon were harvested from New Zealand white rabbits. Cells grown from these tissues were then investigated for their susceptibility to genetic alteration by these vectors in vitro. Based upon their ability to convert cells in culture to a lacZ(+) phenotype, adenovirus was the most effective vector in short-term experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells could be increased by the use of the selectable marker gene neo^r. In an in vivo marker study, we injected adenovirus into the rabbit patellar tendon. Transduced cells could be observed preferentially in the subsynovial layer at a declining frequency over a 6-week period. The allogeneic transplantation of in vitro retrovirally transduced fibroblasts into the patellar tendon resulted in a greater number of transduced cells. Although the number of lacZ(+) cells declined with time, positive cells were still present 6 weeks after transplantation. Furthermore, the transplanted cells, unlike cells transduced in situ with adenovirus, migrated from the injection site and integrated into the crimp of the tendon. Received: 24 July 1996 Accepted: 7 January 1997     

Production of insulin resistance by hyperinsulinaemia in man

Summary It has been proposed that hyperinsulinaemia may cause or exacerbate insulin resistance. The present studies were undertaken to test this hypothesis in man. Glucose utilization, glucose production, and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations (80 and 1700 mU/l), and monocyte and adipocyte insulin binding were measured in normal volunteers on two occasions: once after 40 h of hyperinsulinaemia (25–35 mU/l) produced by infusion of insulin and once after infusion of saline (75 mmol/l; plasma insulin 10 mU/l). After 40 h of hyperinsulinaemia, glucose utilization and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations were both slightly, but significantly, reduced compared with values observed after the infusion of saline (p<0.05), whereas glucose production rates were unaffected. Monocyte and adipocyte binding were also unaffected. These results indicate that hyperinsulinaemia of the magnitude observed in insulin resistant states, such as obesity, can produce insulin resistance in man. Assuming that human insulin sensitive tissues possess spare insulin receptors and that monocyte and adipocyte insulin binding accurately reflect insulin binding in insulin-sensitive tissues, the decreased maximal responses to insulin and the lack of change in insulin binding suggest that this insulin resistance occurred at a post-binding site.     

Subjective Estimation of Health Literacy—What Is Measured by the HLS-EU Scale and How Is It Linked to Empowerment?

A recently published study introduced a new instrument (HLS-EU) for the measurement of health literacy (HL) and comparative data at population level for this measure across eight European Union (EU) countries, and revealed significant differences in HL at population level. The HLS-EU instrument consists of items that aim to assess respondents’ estimation of difficulties regarding different health-related tasks, and it is therefore a measure of subjective HL. With help of a two-step approach, the present study, which was conducted in Austria, aimed to investigate individual experiences and factors that are associated with high or low values of subjective HL as measured by the HLS-EU scale. In a first step, qualitative data from 20 cognitive interviews for the short version of the HLS-EU scale were analyzed. In a second step, the preliminary results of the qualitative analysis were validated with the help of a standardized survey (n = 800). Results show that subjective HL may be grounded either in high empowerment, including high personal and social skills and resources, or in a lack of health-related experience and reduced critical contemplation but high trust in the health system, which is paired with paternalistic preferences. As a conclusion, it is recommended that research should acknowledge the heterogeneous and multidimensional nature of subjective HL.     

Pathogenesis of hypoglycemia in insulinoma patients: suppression of hepatic glucose production by insulin

To determine the mechanism by which hyperinsulinemia causes hypoglycemia in insulinoma patients, rates of glucose production and utilization, and circulating levels of insulin, glucagon, alanine, lactate, and glycerol were measured in 6 insulinoma patients during development of fasting hypoglycemia and in 8 normal volunteers studied over an identical interval. Initially, insulinoma patients had a greater plasma insulin (42 +/- 9 versus 15 +/- 1 microunits/ml) and glucagon levels (214 +/- 31 versus 158 +/- 21 pg/ml) than normal subjects, P less than 0.05, but their plasma glucose levels (81 +/- 4 mg/dl) and rates of glucose production and utilization (1.71 +/- 0.08 and 1.74 +/- 0.08 mg/kg . min, respectively) were not significantly different from those of normal subjects (93 +/- 2 mg/dl, 1.93 +/- 0.11, and 1.92 +/- 0.13 mg/kg . min, respectively). During a subsequent 8-h fast, glucose production and glucose utilization decreased in both groups, but more markedly in insulinoma patients. Since glucose utilization exceeded glucose production to a greater extent in insulinoma patients than in normal subjects, plasma glucose decreased to 44 +/- 3 mg/dl in insulinoma patients, but only to 84 +/- 1 mg/dl in normal subjects (P less than 0.001). Glucose utilization in insulinoma patients never exceeded that of normal subjects. These results demonstrate that fasting hypoglycemia in the insulinoma patients is usually due to suppression of glucose production rather than to acceleration of glucose utilization, as is widely thought. A direct effect of insulin on the liver is probably responsible, since circulating levels of gluconeogenic precursors are normal and since plasma glucagon increases during development of hypoglycemia in insulinoma patients.     

Guideline for management of postmeal glucose

An estimated 246 million people worldwide have diabetes. Diabetes is a leading cause of death in most developed countries, and is reaching epidemic proportions in many developing and newly industrialized nations. Poorly controlled diabetes is associated with the development of renal failure, vision loss, macrovascular diseases and amputations. Large controlled clinical trials have demonstrated that intensive treatment of diabetes can significantly decrease the development and/or progression of microvascular complications of diabetes. There appears to be no glycaemic threshold for reduction of diabetes complications; the lower the glycated haemoglobin (HbA1c), the lower the risk. The progressive relationship between plasma glucose levels and cardiovascular risk extends well below the diabetic threshold. Until recently, the predominant focus of therapy has been on lowering HbA1c levels, with a strong emphasis on fasting plasma glucose. Although control of fasting hyperglycaemia is necessary, it is usually insufficient to obtain optimal glycaemic control. A growing body of evidence suggests that reducing postmeal plasma glucose excursions is as important, or perhaps more important for achieving HbA1c goals. This guideline reviews the evidence on the harmful effects of elevated postmeal glucose and makes recommendations on its treatment, assessment and targets.     

Acute effects of a glucose load on plasma apolipoproteins A-I, A-II, C-II, and C-III in normal and non-insulin-dependent diabetic men

Changes in plasma levels of apolipoproteins A-I, A-II, C-II, and C-III, cholesterol, triglycerides, glucose, and insulin were studied after administration of a glucose load in six normal subjects and five patients with non-insulin-dependent diabetes mellitus. The main finding of our study was the significantly increased responses of total triglycerides and apolipoproteins C-II and C-III from the baseline values in the normal subjects but not in the diabetic group. High-density lipoprotein cholesterol levels at baseline and after glucose loading were significantly lower in diabetic than in normal subjects. As expected, abnormal glucose tolerance and hyperinsulinemia were observed in the diabetic subjects after the glucose loading. The peak glucose and insulin levels and their decline after the glucose loading were delayed in the diabetic patients. The glucose load did not significantly alter total plasma cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II concentrations in normal and diabetic subjects. The apparent blunted response of total triglycerides and apolipoproteins C-II and C-III in the diabetic subjects may be related to maximal stimulation of synthesis of triglycerides and apolipoproteins C-II and C-III by the hyperglycemia and hyperinsulinemia (or both) present in these patients.     

Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo

To assess whether plasma glycerol could be directly derived from plasma glucose, nine postabsorptive dogs were infused with [U-14C] glucose and [2-3H] glycerol to measure the rates of appearance of plasma glucose and glycerol and the conversion of plasma glucose to glycerol before (basal) and after two hours of infusion of glucose (45 mumol/kg/min). Basally (plasma glucose 4.9 +/- 0.2 mmol/L; plasma insulin 5.9 +/- 0.2 microU/mL), rates of appearance of plasma glucose and glycerol were 20 +/- 2 and 5.9 +/- 1.3 mumol/kg/min, respectively, and 1.6 +/- 0.6% of plasma glycerol was derived from plasma glucose. After glucose infusion (plasma glucose 9.1 +/- 0.7 mmol/L; plasma insulin 21.1 +/- 1.9 microU/mL), the rate of appearance of plasma glycerol decreased 80% to 1.1 +/- 0.3 mumol/kg/min and the percent of plasma glycerol from glucose increased significantly to 6.9 +/- 2.9. However, the absolute rate of conversion of glucose to glycerol did not change (0.09 +/- 0.03 v 0.07 +/- 0.03 mumol/kg/min). We conclude that even under conditions of stimulated glycolysis and inhibited lipolysis, only a small amount of plasma glycerol is derived from plasma glucose. Thus, rates of appearance of plasma glycerol can be used as a measure of rates of overall lipolysis in vivo.     

Effect of intermittent physiologic hyperglucagonemia on postprandial plasma glucose levels in normal man

The ability of glucagon to impair glucose tolerance has been questioned by studies involving infusion of exogenous glucagon during a glucose load. Since such hormone administration may not reflect the physiologic pattern of glucagon secretion and may result in hepatic downregulation to glucagon, the present experiments have examined the effects of intermittent andogenous hyperglucagonemia (induced by episodic infusion of arginine) on plasma glucose profiles of normal man following ingestion of mixed meals. In control studies following meal ingestion, plasma glucose, insulin and glucagon increased respectively 15–30 mg/dl, 30–60 uU/ml and 25–50 pg/ml. When meals were accompanied by arginine infusions, plasma glucagon responses were augmented three to fourfold (p < 0.05). Amplitudes of glycemic excursions during infusion of arginine (345 ± 40 mg/dl) were significantly augmented compared to those observed in control studies (286 ± 34 mg/dl, p < 0.02). These results indicate that intermittent increases in plasma glucagon within the physiologic range can adversely affect postprandial glucose profiles in normal man despite concomitant hyperinsulinemia and suggest that such hyperglucagonemia may contribute to impaired postprandial glucose tolerance in diabetic individuals in whom insulin secretion is deficient.