The steel ball-bearing test: a new test for evaluating protective sensation in the diabetic foot.

AIMS/HYPOTHESIS: The aim of the study was to assess a new steel ball-bearing test as a means of evaluating protective sensation in the diabetic foot. METHODS: Subjects were enrolled for this study as follows: (1) 39 patients (mean age 61.3+/-9.7 years) with neuropathy and prior neuropathic ulcer (Group A); (2) 36 patients (mean age 63.7+/-10.1 years) with neuropathy without neuropathic ulcer (Group B); (3) 34 patients (mean age 52.1+/-10.4 years) without neuropathy (Group C); and (4) 21 healthy volunteers (mean age 46.7+/-8.7 years) (Group D). Neuropathy was diagnosed by means of neuropathy disability score (NDS). The plantar area over the second metatarsal head of each foot was examined with steel ball-bearings of varying diameters. The smallest diameter that the patient could feel was used to define the ball-bearing score (range 1-6). RESULTS: A high ball-bearing score was significantly more frequent in patients with neuropathic ulceration than in neuropathic patients without ulceration and in diabetic patients without neuropathy (p<0.001). A high score was also more frequent in neuropathic patients without ulceration, than in patients without neuropathy (p<0.001). The ball-bearing score was significantly (p=0.01) correlated with the NDS, the monofilament test, the vibration perception threshold and the thermal perception threshold. The ball-bearing test had a sensitivity of 84% and a specificity of 100% for impaired protective sensation due to neuropathy, and a sensitivity of 84.6% and a specificity of 86.1% for detection of patients with prior neuropathic ulceration. CONCLUSIONS/INTERPRETATION: The steel ball-bearing test has a high sensitivity and specificity both for the evaluation of protective sensation and for detection of patients with prior neuropathic ulceration.

Surveillance as a starting point to reduce surgical-site infection rates in elective orthopaedic surgery.

A surveillance programme was started after a period of high infection rates in an orthopaedic surgical department. The programme was aimed at reducing infection rates in elective hip and knee replacement procedures, and at creating awareness of infection control practices in an acute hospital. Possible causes of the initial high infection rates were analysed and discussed with healthcare workers involved in orthopaedic surgery. No specific cause could be found but substantial logistic improvements were achieved by studying for five years that may have contributed to the reduction of postoperative infections. Surveillance is an important part of any hospital-acquired infection surveillance programme. Its success depends on the ability of the infection control practitioner (ICP) to form a partnership with the surgical staff. Creating a sense of ownership of the surveillance initiative amongst the surgical staff enhances co-operation and ensures that the best use is made of the information generated. It is not possible to eliminate surgical-site infections (SSI) completely, but by a process of sharing information we have been able to influence behaviour to reduce the incidence of SSI.

Voice recognition software versus a traditional transcription service for physician charting in the ED.

This study was conducted to compare real-time voice recognition software to a traditional transcription service. Two emergency department (ED) physicians dictated 47 charts using a voice dictation software program and a traditional transcription service. Accuracy, word per minute dictation time and turnaround time were calculated from the data. The transcription service used in our study was more accurate than the voice recognition program with an accuracy of 99.7 percent versus 98.5 percent for the voice recognition program. The average number of corrections per chart was 2.5 for the voice recognition program and 1.2 for the traditional transcription service. Turnaround time was much better using the computer voice recognition program with an average turnaround time of 3.65 minutes versus a turnaround time of 39.6 minutes for the traditionally transcribed charts. The charts dictated using the voice recognition program were considerably less costly than the manually transcribed charts. In summary, computer voice recognition is nearly as accurate as traditional transcription, it has a much shorter turnaround time and is less expensive than traditional transcription. We recommend its use as a tool for physician charting in the ED.

Antibiotic-induced release of endotoxin: in-vitro comparison of meropenem and other antibiotics.

The influence of meropenem, a new carbapenem antibiotic, on cell morphology and in-vitro lipopolysaccharide (LPS) release from Escherichia coli was compared with that of imipenem, ceftazidime, tobramycin and ciprofloxacin. Free and cell-associated LPS was quantified by means of a capture ELISA method based on the recognition of E. coli LPS by monoclonal antibodies. Microscopically, meropenem was found to induce spheroplast formation similar to that seen with imipenem, while ceftazidime and ciprofloxacin induced filament formation. Free and cell-associated LPS levels were low in the presence of meropenem, imipenem, ciprofloxacin and tobramycin, but high in the presence of ceftazidime. Reduced endotoxin release appears to be a common property of carbapenem antibiotics. Morphological changes in bacteria in the presence of antibiotics do not predict their LPS-liberating effect since ciprofloxacin induced low levels of LPS despite causing filament formation.

Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological changes and endotoxin-liberating effects.

The in vitro effects of meropenem on Pseudomonas aeruginosa were examined by studying (i) the inhibitory and bactericidal concentrations of meropenem versus those of imipenem for clinical isolates; (ii) changes in bacterial morphology during in vitro culture; and (iii) release of endotoxin induced by meropenem compared with that induced by other antipseudomonal compounds. Meropenem MIC90 and MBC90 values for 108 clinical isolates were 2 and 4.8 mg/l compared to 4.5 and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and scanning electron microscopy showed that meropenem induced the formation of indeterminate bacterial cell forms at drug concentrations of 1-2.5 mg/l (0.5- to 1.25-fold the MIC), while spheroplasts predominated at drug levels exceeding 5 mg/l (2.5-fold the MIC). Determination of free and EDTA-releasable endotoxin activity by means of the Limulus lysate test showed that both meropenem and imipenem liberated significantly less endotoxin than did ceftazidime. Therefore, although meropenem binds to penicillin-binding proteins (PBPs) 2 and 3 (in contrast to imipenem, which binds to PBP2 only), endotoxin release should not be a cause of concern when treating systemic gram-negative infections with this drug.

Assessment of insulin action in man: role of hyperglycemia.

The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg.kg-1.min-1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg.kg-1.min-1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg.kg-1.min-1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin-stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action.

Glucoregulatory function of thyroid hormones: interaction with insulin depends on the prevailing glucose concentration.

The effect of elevated serum thyroid hormone concentrations on insulin-induced glucose metabolism was studied in healthy subjects before and after T4 administration (250 micrograms T4/day for 10-14 days). This treatment induced moderate hyperthyroidism (T4, 15.2 micrograms/dl; T3, 200 ng/dl). The following results were obtained. Insulin receptor binding to a 90% enriched monocyte fraction or to mitogen-stimulated cultured T lymphocytes was decreased by T4 administration, whereas insulin binding to erythrocytes was unaffected. Despite down-regulation of cellular insulin receptors, T4 administration did not alter oral glucose tolerance, but increased the disappearance of glucose after an iv load and the amount of glucose metabolized during euglycemic clamp studies infusing 1.0 or 1.5 mU insulin/kg BW X min; no effect was found at insulin infusion rates of 0.5, 2.0, and 4.0 mU/kg X min. At increasing steady state plasma glucose levels (up to 175 mg/dl) and an insulin infusion rate of 1.0 mU/kg BW X min, T4 administration reduced insulin-induced glucose metabolism. We conclude that experimental hyperthyroidism decreases insulin receptor binding but increases insulin-induced glucose metabolism during euglycemia. This may be due to the direct effect of thyroid hormones on glucose metabolism; however, during hyperglycemia, thyroid hormone induced insulin resistance is unequivocal.

[Clinical experiences with the substitution of biosynthetic human insulin in children and adolescents with type I diabetes]. / Klinische Erfahrungen mit der Substitution biosynthetischen Humaninsulins bei Kindern und Jugendlichen mit Typ-I-Diabetes.

The therapeutic efficiacy of biosynthetic human insulin (BHI) is compared to that of porcine insulin into groups of 10 children each with so far untreated type I diabetes. No significant difference between the two groups could be demonstrated throughout the first months of treatment: both the initial substitution dose, and the rate of partial remission were similar. However, the regimen of the BHI treated patients had to be changed to two injections a day earlier, since BHI given subcutaneously results in a faster and shorter lasting response than porcine insulin. Thus, after 9 and 12 months of treatment a higher BHI dose than porcine insulin dose had to be given. Thirty children pretreated with regular and NPH porcine insulin, who were in the post remission period, were transferred to BHI. First, the needed dose of insulin was significantly reduced. Two to three months later, however, the need in insulin increased, so that after 9 and 12 months the original dose had to be given again. The relationship between morning (2/3) and evening (1/3) dose was constant and in the morning as well as in the evening the ratio between regular and NPH-BHI was 40%/60%. There was no significant improvement or deterioration after replacing porcine by human insulin, since both insulins have the same metabolic effects.

[Effect of pregnancy on maternal carbohydrate and lipid metabolism. II: Changes in lipid and carbohydrate metabolism as well as hormonal changes following intravenous glucose administration]. / Untersuchungen zum Einfluss der Schwangerschaft auf den Kohlenhydrat- und Fettstoffwechsel der Mutter. Teil II: Anderungen im Lipid- und Kohlenhydratmetabolismus sowie hormonale Veränderungen nach intravenöser Glucosegabe.

The following parameters of glucose biokinetics in pregnancy, in which the behavior of the glucose in the steady state is described, were investigated mathematically following short-term disturbance of the steady state of the maternal metabolism by intravenous administration of glucose. The glucose assimilation coefficient (KG) is unchanged in pregnancy. However, both during pregnancy and post partum (2.30; 2.20; 2.36; 1.79 [%/min]), the values are higher than in the non-pregnant control group (1.2%/min). Analogously to these findings, the glucose distribution space increases during pregnancy from 13 liters to 16.3 liters, decreasing post partum to 13.4 liters. The easily exchangeable glucose pool, i.e., the quantity available for assimilation in the distribution space, is unchanged during pregnancy; nor is there any change as compared to the non-pregnant and postpartal control groups. Glucose transfer, i.e., the glucose quantity which enters or leaves the pool per unit of time, is increased during pregnancy (0.45; 0.444; 0.47 [g/kg/h]) as compared to the non-pregnant and postpartal controls (0.25; 0.35 [g/kg/h]). The findings above indicate that the maternal glucose metabolism is increased during pregnancy. Owing to the lipolytic effect of HPL, the mother is obliged to meet a portion of her energy requirements from the lipid metabolism, so that there is enough glucose available for the fetus. HPL appears to develop this glucose-saving effect doubly.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin binding and degradation studies on erythrocytes at different temperatures.

Insulin binding of human erythrocytes has been investigated between 0 and 37 degrees C using porcine 125I-insulin/unlabeled porcine insulin and mono [125I] (Tyr-A14)biosynthetic human insulin/ unlabeled biosynthetic human insulin, respectively. Either system exhibited a regular thermodynamical behavior between 0 and 22 degrees C, giving unitary free-energy changes of about -58/ -59 kJ/mol, unitary entropy changes of about +55/ +70 J/K per mol and a reaction heat of -43.1/ -38.3 kJ/mol. From 22 up to 37 degrees C an irregular thermodynamical behavior could be observed, which can be partially explained by an increased insulin degradation during incubation and an additional time-dependent binding of the degradation products.

Insulin binding to erythrocytes before and after changing from porcine to biosynthetic human insulin in children with type-I diabetes.

The binding of [125I]insulin to isolated erythrocytes from diabetic children (n = 27) before (group a) as well as one and five months after changing from porcine to biosynthetic human insulin (groups b and c) was investigated. An analysis of variance of the binding parameters, determined by a nonlinear regression procedure, yielded statistically significant differences between the receptor affinities Ka as well as between the receptor concentrations Xo of the groups a and b, a and c and b and c. (formula: see text). The results suggest that the change from porcine insulin to biosynthetic human insulin induces a short-term as well as long-term increase in the affinity, and a decrease in the concentration of the erythrocyte insulin receptors.

Insulin binding to erythrocytes in children with type-I diabetes mellitus.

Specific binding of [125I]insulin to isolated erythrocytes was investigated in four groups of children (A) Healthy children under 10 years of age (n = 20) (B) Healthy children over 10 years of age (n = 13) (C) Diabetic children under 10 years of age (n = 12) (D) Diabetic children over 10 years of age (n = 63). In addition, all diabetic children (n = 75) were subdivided into four groups according to the duration of diabetes. (E) less than 2 years, (F) 2--4 years, (G) 4--6 years, and (H) greater than 6 years. By means of a nonlinear regression analysis for the extraction of binding parameters (assuming a single receptor class model with independent receptor sites) and methods of variance analysis, statistically significant differences were observed for the receptor affinities Ka (10(8) l/mol) and the receptor concentrations X0 (nmol/l) between groups A and C, B and D, C and D, but not between A and B. The affinities of groups C and D were found to be higher than the corresponding values of groups A and B, whereas the receptor concentrations exhibited an inverse behaviour. A significant increase of the receptor concentration and decrease of the receptor affinity depending on the duration of diabetes could only be proved to exist during the first 2 years of the disease.

[Diabetes specific hand changes (cheiropathy) in children and adolescents with insulin-dependent diabetes (type I)]. / Diabetesspezifische Handveränderungen (Cheiropathie) bei Kindern und Jugendlichen mit insulinbedürftigem Diabetes (Typ I).

215 children and adolescents with insulin dependent diabetes (age: 12(6)/12 +/- 3(9)/12 yrs; duration of diabetes 4(5)/12 +/- 3(9)/12 yrs, daily insulin requirement: 0.74 +/- 0.26 I.U./kg b.w.) were investigated for the presence of hand changes (cheiropathy) due to diabetes. Controls were 110 healthy persons of similar age (age: 11(5)/12 +/- 4(8)/12 yrs). Signs of cheiropathy were found in 44 (20.5%) of the diabetics. In 28 of these diabetics reduced mobility of the proximal and/or distal interphalangeal joints of one finger and in 16 others of at least two fingers was observed. No pathological alterations were found in the wrists, shoulder joints or spine. Mild signs of cheiropathy were seen in 5 (4.5%) of the controls. A significant positive relationship was found between age and duration of diabetes and the severity of cheiropathy. Diabetics with cheiropathy also had significantly higher daily insulin requirements than others. Of 49 patients with good diabetic control only one (2.0%) had signs of cheiropathy. In the group of 82 diabetics with fair control 12 (14.6%) showed hand changes, in the group of 84 patients with poor control 31 (36.9%). Cheiropathy must be considered to be a prognostic indicator of impending microangiopathy (retinopathy, nephropathy and neuropathy) in diabetic children and adolescents.

[Diabetes-specific hand changes in type I diabetes mellitus]. / Diabetes-spezifische Handveränderungen bei Diabetes mellitus vom Typ I.

Diabetes-specific hand alterations (cheirarthropathy) were observed in 44 out of a total of 215 children and adolescents with insulin-dependent diabetes. In 28 of them limitations of movement in the proximal or (and) distal interphalangeal joints of one finger, and in the remaining 16 patients changes of at least two fingers were seen. Hand and shoulder joints or the vertebral column were not affected. In a control group of 110 probands without metabolic disorder only five showed cheirarthropathy. The frequency of diabetes-specific alterations of the hand increased with the age of the patients, the duration of diabetes and insulin requirements. In particular, the quality of metabolic control is of paramount importance for the as yet unclear pathogenesis of cheirarthropathy.

Insulin binding to erythrocytes after acute 16-methyleneprednisolone ingestion.

The binding of [125I]insulin to erythrocytes, glucose and insulin were determined before and 1, 7 and 35 days after ingestion of 2 X 60-methyleneprednisolone. None of two groups of volunteers (7 males, 4 females showed clear alterations of the insulin binding parameters (Ka and R0), or of the fasting cortisol, glucose and insulin concentrations. These results exclude the possibility that the diabetogenic effect of glucocorticoides is accompanied by an alteration of the insulin receptor characteristics of erythrocytes.

Renal handling of homologous and heterologous insulin in the isolated perfused rat kidney.

1. Renal handling of pig- and rat-insulin was studied in the isolated perfused rat kidney. 2. Metabolic clearance rates of both pig- and rat-insulin exceeded GFR. 3. Peritubular uptake of pig-insulin accounted for 13% of rat-insulin for 31% of the total metabolic clearance. 4. The nonfiltering kidney does not remove insulin from the peritubular circulation. 5. Metabolic clearance rates of pig- and rat-insulin are directly related to GFR. 6. The filtration process seems to be necessary for the uptake of insulin at the peritubular site.

[C-peptide excretion in 24 hours-urine as an indicator of B-cell residual function in children and adolescents with type-I-diabetes (author's transl)]. / Die C-Peptidausscheidung im 24 Std-Urin als Indikator der B-Zell-Residualfunktion bei Kindern und Jugendlichen mit Typ-I-Diabetes.

In 140 juvenile diabetics residual B-cell-function was measured according to the amount of the immunoreactive C-peptide (IRCP) in the 24 h-urine. We were able to repeat this test after two years in 69 of these patients. All diabetic children showed maintained residual insulin secretion (mean +/- S mean 2.60 +/- 0.31 nmol/24 h). There was a significant negative relationship (p less than 0.001) between the duration of diabetes and the extend of the residual B-cell-function. C-peptide urine excretion of the diabetics who were followed up dropped significantly (0.08 down to 0.02 nmol/kg/24 h, p less than 0.001), and the daily insulin requirement increased significantly (0.36 to 0.67 U/kg, p less than 0.05). In comparison, children with a shorter duration of the diabetes (less than 3 years) showed a more rapid decrease of their residual B-cell function with a simultaneously greater increase of the daily insulin dose as opposed to children with the diabetes for longer than 3 years at the time when they were first seen. With a short course of diabetes the decrease of the C-peptide and the increase of the daily insulin dose were negatively correlated (p less than 0.001). The clinical phenomena of the remission period as known until now are related to the decline of B-cell function.