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Biomedical subjects

M Sperlich

Publications and source records attributed to M Sperlich.

At least 19 recordsLinked to original sources

Information technology and home glucose clamping.

Persons with diabetes are responsible for the day-to-day control of their glycemia. To assist patients in discharging this responsibility and help them achieve and sustain improvements in self-blood glucose control, we developed information technology capable of executing algorithms for "clamping glucose" at home. Algorithms for laboratory glucose clamping were translated and adapted for use by patients. The procedures were supported by a central computer and registry. Interaction with the algorithms from home required the patient to handle only a touch-tone telephone, which accessed voice response hardware in the central computer. Patients reported self-measured blood glucose levels or hypoglycemia symptoms together with dietary changes, planned exercise, stress, illness or other lifestyle events. In response, they received self-management instructions and dosing decision support. Metabolic end points were measured. System beta testing in active patients was for 1 year. Patients (n = 142) used the algorithms for their daily self-management, accumulating 1,651 patient-months of follow-up. Almost 100,000 telephone calls were received. Patients benefited. Prevalence of diabetes related crises (hyperglycemia > 400 mg/dL, hypoglycemia < 50 mg/dL or symptoms without measurement) fell approximately twofold (p < 0.05) and glycated hemoglobin levels fell 1.3% (p < 0.001), while body weight was stable. Providers benefited from the timely receipt of standardized reports to monitor the progress of their patients. Earlier intervention was possible. Information technology facilitated home glucose clamping whereby patients with diabetes received timely assistance, advice and decision support for crucial self-control of blood glucose levels. This empowered patients to achieve independence and improve diabetes self-management.

Algorithms↗

The impact of initiatives in education, self-management training, and computer-assisted self-care on outcomes in diabetes disease management.

The purpose of this work is to elucidate the advantages and disadvantages arising from three distinct diabetes disease management initiatives in a managed care setting. The initiatives included (1) education alone, (2) education with self-management training, and (3) education with computer-assisted self-care. Outcomes of interest were changes in glycated hemoglobin (HbA1c), body weight, and costs of care in each cohort of care recipients. A total of 978 health plan members with diabetes within a mixed model HMO were included in the initiatives for improving blood glucose control. HbA1c was measured at baseline and at 3 and 12 months, body weight at baseline and 12 months, and costs of care over 1 year. Costs were derived from suppliers and the health plan. The design is a longitudinal observation study. With the edu-cation-alone initiative, costs, HbA1c, and body weight were unchanged. When education is supplemented with ongoing self-management training, HbA1c fell 1.1% (p < 0.01), body weight rose by 11 kg (p < 0.01), and costs for care increased by $18 per member per month. When education is supplemented with ongoing computer-assisted self-care, HbA1c also dropped by 1.1% (p < 0.01), body weight was unchanged (p > 0.4), and costs for care were $1.31 per member per month. All initiatives improved glycated hemoglobin. Other outcomes must therefore be considered. Among the initiatives, this study elucidated significant differences in body weight and costs. Therefore, in choosing a diabetes disease management program, it would appear that costs should be the primary consideration and methodologies that control body weight should be a priority.

Body Weight↗

Childhood onset of GH deficiency: reassessment of GH status and effects of substitution.

The final height of 77 patients with growth hormone (GH) insufficiency of childhood onset was analysed. Patients were treated between 1968 and 1996 for 1-15 years. The mean final height in patients with severe GH deficiency was 163.9 cm (males) or 151.1 cm (female patients). In patients with partial GH insufficiency, the mean final heights were 166.2 and 157.7 cm, respectively, and in patients with GH deficiency caused by intracerebral tumours, 175.9 or 160.2 cm, respectively. Late established diagnosis, lack of (pituitary) GH during the time prior to 1980 or low frequency of injections per week were related to the fact that final height was often below the target height range. In four of 51 retested patients with childhood onset GH deficiency, a normal response of the pituitary gland to pharmacological testing was found, whereas all other patients still suffered from GH insufficiency. An increased amount of fat and a decreased amount of lean body mass as well as low bone mineral density (12 out of 15 patients) could be demonstrated at re-evaluation.

Adolescent↗

Small bowel tissue high-energy phosphate regeneration after 7 hr of cold ischemic storage: comparison of University of Wisconsin and Eurocollins solutions.

As adenine nucleotide content has been shown to correlate with post-transplant function of livers and hearts, it was the aim of our study to investigate the regeneration of rat small bowel tissue high-energy phosphates after 7 hr of cold storage followed by incubation of everted small bowel sacs in normothermic oxygenated KHB for 1 hr. We compared the University of Wisconsin (UW) and the Eurocollins (EC) solutions. Krebs-Henseleit-bicarbonate buffer (KHB) was used to point out the effect of simple cold ischemic storage. After 7 hr of cold storage only small bowel stored in UW and EC solutions retained the capacity for almost total regeneration of ATP necessary for optimal posttransplant function, whereas in the KHB group we found only minimal regeneration. A similar pattern was found for the energy charge. These data support the superiority of UW and EC solutions over simple cold storage in KHB for preservation of small bowel.

Adenosine↗

Final height and predicted height in boys with untreated constitutional growth delay.

We report on 49 boys with constitutional growth delay (CGD) who were initially seen in our clinic at a mean chronological age of 13.3 years (range, 7.3-16.4) and a bone age of 11.1 years (range, 6.0-13.5). All were below the 5th height percentile for chronological age. A positive family history with delayed growth and puberty in one or both parents could be elicited in 75%. All 49 patients were re-examined at a mean age of 22.9 years (range, 20.4-31.2). Measured final height was 171.3 cm (range, 161.2-181.7), which was slightly, but significantly lower than mean target height of 173.0 cm. Final height expressed as standard deviation score (SDS) of a male adult population standard was -1.0 (range, -2.4 to 5), also significantly lower than initial height SDS related to bone age (SDSBA) of -0.5 (range, -1.6 to 2). If related to target height (Tanner), final height was found to correlate positively with the initial bone age deficit and the initial height SDSBA. Observed final height was also compared with the predicted adult height by the methods of Bayley-Pinneau (BP), Tanner-Whitehouse Mark II (TW II) and Roche-Wainer-Thissen. Regression equations between all three prediction methods and final height showed an excellent correlation (P < 0.0001). However, only by the BP method was predicted height very close to and no different from measured final height (paired t-test). Despite this, final height in 16 of 49 patients (32.6%) differed by more than 5.0 cm from BP predicted height.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Administration of atracurium during reperfusion of rat livers after 21 h of cold ischaemic storage in different solutions.

The pharmacokinetics of atracurium are not altered by impaired hepatic function. The drug is therefore used widely in liver transplant patients. In previous work on the hepatotoxic effects of atracurium in an isolated, perfused rat liver model, we could not detect biochemical (release of lactate dehydrogenase or aspartate aminotransferase) or histological evidence of liver cell damage, except a reduction in hepatic tissue ATP content. In the present study, rat livers were reperfused with Krebs-Henseleit bicarbonate buffer with or without atracurium after 21 h of cold ischaemic storage in University of Wisconsin (UW), Bretschneider's HTK or Euro-Collins solution. UW-protected livers showed a complete restoration of ATP, total adenine nucleotides and energy charge during reperfusion, but the addition of atracurium diminished the regeneration capacity to about 50%. The energy charge (an index for determination of liver viability) was also reduced markedly.

Adenine Nucleotides↗

Influence of incubated atracurium on rat liver function.

Degradation of atracurium by Hofmann elimination and ester hydrolysis depends mainly on pH and temperature and is said to be independent of liver and kidney function. Consequently atracurium is used widely in patients with liver failure. However, there is evidence that incubation of atracurium at 37 degrees C and pH 8 leads to leakage of LDH from hepatocyte cell cultures. We have tested the hepatotoxic effects of incubated atracurium in an isolated perfused rat liver model. After equilibration, atracurium 2010 mumol ml-1 (preincubated at pH 8 and 37 degrees C for 120 min) was administered over a period of 10 min followed by perfusion of Krebs-Henseleit bicarbonate buffer for 60 min. We found that incubation resulted in considerable degradation of atracurium and formation of laudanosine. Administration of incubated atracurium did not produce either biochemical or morphological damage to liver cells, but caused considerable increase in bile flow. We conclude that administration of preincubated atracurium did not produce impairment of liver cell function. The increase in bile flow could be beneficial if it occurs clinically.

Animals↗

Proton spin-lattice relaxation time as liver transplantation graft viability parameter.

In this study proton NMR T1 of stored rat liver grafts was investigated and correlated with other viability parameters. Five different storage solutions were used and T1 as well as overall tissue water content, bile flow, and energy charge were determined after various periods of cold storage (1 to 48 hr). A good correlation between T1 and tissue water content was detected, suggesting the possible use of this relaxation time parameter as liver graft viability parameter in a combined protocol of rapid viability assays for human liver transplantation surgery.

Adenosine↗

Proton spin-spin relaxation times as liver transplantation graft viability parameter.

In this study, spin-spin relaxation time T2 of stored rat liver grafts was investigated and correlated with other viability parameters. Five different storage solutions were applied and T2 as well as overall tissue water content, bile flow, and energy charge were determined for increasing durations of cold storage (1-48 hr). Good correlation between T2 and tissue water content was detected. In a subset of experiments, dealing with additional warm ischemia after cold storage, the relative increase of T2 and energy charge showed a very good correlation. The results suggest the possible use of relaxation time parameters as liver graft viability parameters in a combined protocol of rapid viability assays for human liver transplantation surgery.

Animals↗

Comparison of HTK- and UW-solution for liver preservation tested in an orthotopic liver transplantation model in the pig.

The aim of this experimental study was to compare the preservation potency of University of Wisconsin (UW) and HTK (Bretschneider) solutions in an orthotopic liver transplantation (OLT) model in pigs. Livers were harvested using an in situ perfusion technique, where organs were flushed with the solution being tested, stored on ice--cold storage (CS)--for 2 or 24 h and then transplanted. Parameters monitored were liver enzymes in serum, hepatic water content, high energy phosphates, nuclear magnetic resonance (NMR) relaxation time T2, light microscopy and bile production. CS for 24 h is an extreme in pig liver preservation and is not compatible with animal survival. Biopsies showed drastic morphological changes and grafts did not produce bile in either group. (Bile production 2 h CS: HTK, 5.6 +/- 1.8 ml/h; UW, 4.7 +/- 2.3 ml/h) Enzyme release after reperfusion (deltaSGOT, deltaLDH) was higher in long-term preservation. Hepatic tissue water content significantly decreased during CS in UW preserved livers. Edema alter reperfusion (deltaH2O: HTK 24 h = +5.6%, UW 24 h = +4.8%) and regeneration capacity after reperfusion (UW 2 h = 63%, HTK 2 h = 55%, UW 24 h = 30%, HTK 24 h = 30%) were not significantly different. However, we did not observe major differences in preservation potency between the solutions tested. Differences were correlated, rather, with length 9 time of CS, than with the solution used. Therefore, HTK solution seemed to be a low potassium containing alternative to UW solution.

Adenosine↗

Hepatotoxicity testing of atracurium and laudanosine in the isolated, perfused rat liver.

The pharmacokinetics of atracurium, which is degraded by Hofmann decomposition and ester hydrolysis, is not altered by impaired liver function. Atracurium should, therefore, be ideal for patients with heptic failure, and is now widely used in clinical practice. However, some studies reported considerable hepatotoxicity after atracurium, especially from its breakdown products--for example, leakage of lactate dehydrogenase (LDH) from isolated rat hepatocytes. Therefore, we have studied, in an isolated perfused rat liver model, biochemical and morphological changes after administration of either atracurium or its main metabolite, laudanosine. Despite using extremely high concentrations of these substances, we could not detect, biochemically (release of LDH or aspartate amino-transferase (AST)) or histologically, any signs of liver cell damage.

Animals↗