Oral cyclosporine A treatment is feasible after myeloablative conditioning in allogeneic hematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: The target level and route of administration of cyclosporine A (CsA) differ between transplantation centres. It is unclear whether oral CsA is sufficient to maintain target level of CsA. CASE SUMMARY: We retrospectively analysed data from 48 adult patients, who underwent myeloablative hematopoietic stem cell transplantation. Twenty-one patients (44%) tolerated CsA orally throughout the transplantation period without increased incidence of acute graft versus host disease(aGVHD). Low concentration of CsA in week 2 was associated with increased incidence of aGVHD. WHAT IS NEW AND CONCLUSION: Oral administration of CsA is safe, less time-consuming and economically advantageous. Close monitoring of CsA concentration is important.

Validation of the type 1 diabetes distress scale (T1-DDS) in a large Danish cohort: Content validation and psychometric properties.

Aim: To validate the Type 1 Diabetes Distress Scale (T1-DDS) in a large sample of adults with Type 1 diabetes (T1D) from diabetes clinics in Denmark. Methods: Altogether 40 adults with T1D were interviewed to explore the content of T1-DDS in a Danish setting and to validate the translation of the T1-DDS into Danish. Subsequently, a survey including T1-DDS, the Problem Areas In Diabetes scale (PAID-20), fear of hypoglycemia, social support, and diabetes duration was answered by 2201 people with T1D. Other person characteristics were collected from the National Patient Register. HbA1c was obtained from the Clinical Laboratory Information System. Data distribution, internal consistency, convergent and construct validity, factor structure, three weeks retest, and cut-points were explored. Results: Interview data supported the relevance of all T1-DDS items for the assessment of diabetes distress among adults with T1D. The T1-DDS showed good content and acceptable construct validity, and the ability to detect high diabetes distress levels. A high correlation between T1-DDS and PAID-20 (rho = 0.91) was found. The retest scores showed a good reliability (all rho ≥0.68) with the highest variability in the Friends/Family Distress and Physician Distress subscales and the lowest variability in the Powerlessness and Eating Distress subscales of the T1-DDS. Qualitative findings pointed out relevant concerns of people with T1D, which were not included in the T1-DDS. Conclusion: The study supports the use of the Danish T1-DDS, but also highlights that existing diabetes distress questionnaires including T1-DDS do not cover all potential diabetes stressors and worries.

Increased performance of secondary clarifiers using dynamic distribution of minimum return sludge rates.

Most wastewater treatment plants have several secondary clarifiers or even more sets of clarifiers including several secondary clarifiers, and in practice it is a well known problem that equal distribution of the load to the single clarifier (or set of clarifiers) is very difficult-not to say impossible-to obtain. If the problem is neglected, quite a big percentage of the total clarifier capacity-measured as the max. allowed hydraulic load-can be lost. Further, return sludge rates are seldom controlled by any other means than as a (typically too high) percentage of the inlet to the wastewater treatment plant-giving a varying and too low suspended solids concentration in the return sludge, which again can lead to an unnecessary use of polymer in the pre-dewatering of the surplus sludge taken from the return sludge. A control of the return sludge rate divided into two parts - control of the total return sludge flow and control of how the total flow shall be distributed between the secondary clarifiers - is able to solve the mentioned problems. Finally, as shall be demonstrated on full scale wastewater treatment plants, a considerable increase of the hydraulic capacity of the treatment plants can be obtained.

Cardiac surgery patients present considerable variation in pre-operative hemodynamic variables.

BACKGROUND: It is essential to control hemodynamics in cardiac surgery. Patients are often monitored extensively in order to optimize hemodynamic performance. However, pre-operative values are normally unknown. Furthermore, hemodynamic goals may seem arbitrary and the lack of an evidence-based consensus may lead to both under- and over-treatment. The aim of this study was to evaluate the variables most commonly used for hemodynamic guidance in the post-operative period. METHODS: Ten patients scheduled for elective cardiac surgery were followed with invasive hemodynamic monitoring the night before surgery. All data were recorded automatically and electronically. RESULTS: We found considerable inter-patient differences and intra-patient variation. The greatest intra-patient variation was found in the cardiac index (CI), ranging from 1.9 to 5.3 l/min/m(2). Four patients had periodic CI <2.4 l/min/m(2). Eight patients showed SpO2 values < or =92, four of them in more than 15% of the observations. Six patients had an SvO2 <70% in more than 40% of the observations and two an SvO2 < 64% in more than 20% of the observations. CONCLUSIONS: This study is unique because hemodynamic reference data in cardiac surgery patients have not been published previously. The intra-patient variations were unexpectedly high in most hemodynamic variables and demonstrate the difficulties of using hemodynamic parameters as a guidance for treatment and indicate that goal-oriented therapy using currently accepted values may result in over-treatment in some patients.

A mathematical model approach quantifying patients' response to changes in mechanical ventilation: evaluation in volume support.

This paper presents a mathematical model-approach to describe and quantify patient-response to changes in ventilator support. The approach accounts for changes in metabolism (V̇O2, V̇CO2) and serial dead space (VD), and integrates six physiological models of: pulmonary gas-exchange; acid-base chemistry of blood, and cerebrospinal fluid; chemoreflex respiratory-drive; ventilation; and degree of patients' respiratory muscle-response. The approach was evaluated with data from 12 patients on volume support ventilation mode. The models were tuned to baseline measurements of respiratory gases, ventilation, arterial acid-base status, and metabolism. Clinical measurements and model simulated values were compared at five ventilator support levels. The models were shown to adequately describe data in all patients (χ(2), p > 0.2) accounting for changes in V̇CO2, VD and inadequate respiratory muscle-response. F-ratio tests showed that this approach provides a significantly better (p < 0.001) description of measured data than: (a) a similar model omitting the degree of respiratory muscle-response; and (b) a model of constant alveolar ventilation. The approach may help predict patients' response to changes in ventilator support at the bedside.

A mathematical model approach quantifying patients' response to changes in mechanical ventilation: Evaluation in pressure support.

PURPOSE: This article evaluates how mathematical models of gas exchange, blood acid-base status, chemical respiratory drive, and muscle function can describe the respiratory response of spontaneously breathing patients to different levels of pressure support. METHODS: The models were evaluated with data from 12 patients ventilated in pressure support ventilation. Models were tuned with clinical data (arterial blood gas measurement, ventilation, and respiratory gas fractions of O2 and CO2) to describe each patient at the clinical level of pressure support. Patients were ventilated up to 5 different pressure support levels, for 15 minutes at each level to achieve steady-state conditions. Model-simulated values of respiratory frequency (fR), arterial pH (pHa), and end-tidal CO2 (FeCO2) were compared to measured values at each pressure support level. RESULTS: Model simulations compared well to measured data with Bland-Altman bias and limits of agreement of fR of 0.7 ± 2.2 per minute, pHa of -0.0007 ± 0.019, and FeCO2 of -0.001 ± 0.003. CONCLUSION: The models describe patients' fR, pHa, and FeCO2 response to changes in pressure support with low bias and narrow limits of agreement.

Early periprosthetic femoral bone remodelling using different bearing material combinations in total hip arthroplasties: a prospective randomised study.

The present study was performed to test the hypothesis that different bearing materials have an impact on femoral bone remodelling within the first year after a total hip arthroplasty. A total of 225 patients with osteoarthrosis of the hip or avascular necrosis of the femoral head were included in this randomised prospective study. All patients had an identical hybrid total hip arthroplasty (cemented BiMetric stem and cementless RingLoc acetabular cup) except for the bearing materials: polyethylene-on-zirconia (n = 78), CoCr-on-CoCr (n = 71), or alumina-on-alumina (n = 76). Bone mineral density (BMD) was measured with Dual-energy X-ray absorptiometry (DEXA) in seven Gruen zones adjacent to the femoral implant. The DEXA scan was performed within one week after surgery and was repeated one year postoperatively. There was no significant difference in periprosthetic BMD change between the three groups. After twelve months the relative BMD decrease was highest in the proximal part of the femur, - 6.2% in the greater trochanter region and - 12.7% in the lesser trochanter region. In the distal zones the relative BMD decrease was -5.3, -4.2, -2.1, -2.3, and -5.6%, respectively. The use of different bearing materials had no significant impact on femoral bone remodelling adjacent to the cemented hip stem within one year after surgery.

On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats.

In laboratory animals as well as in human beings a depth of anaesthesia, where the subject has no pain or recall of events from the surgery, should be provided. Haemodynamic parameters such as heart rate and blood pressure are not a guarantee for an optimal depth of anaesthesia, especially when using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia in rats. The AEP was elicited with a click stimulus and monitored in an 80 ms window synchronised to the stimulus. The AEP was extracted applying an Auto Regressive Model with Exogenous Input (ARX-model) from which a Depth of Anaesthesia Index (DAI) was calculated. DAI was normalised to 100 while awake and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet. and Dormicum were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously with the AEP. The results showed that in four rats DAI decreased to a level below 30 while anaesthetised. In the remaining five rats the AEP was only decreased to a level below 45. The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual rats. The decrease in the DAI correlated well with the loss of stimulus response. In conclusion, MLAEP could be used as an indicator of depth of anaesthesia in rats during Hypnorm vet. and Dormicum administration. However studies applying other anaesthetic drugs should be carried out, before a conclusion of the general utility of the method can be made.

Elektra prosthesis for trapeziometacarpal osteoarthritis: a follow-up of 39 consecutive cases.

We present a prospective follow-up of 39 Elektra prostheses in 37 patients (32 women and five men), with a mean age of 56.5 (range 46-71) years; 34 patients had osteoarthritis and three had rheumatoid arthritis. Patients were followed using clinical examination, including measurement of pain on a visual analogue scale, mobility, and strength, after 6, 12, 26, and 52 weeks, and annually thereafter. Radiological examination was done preoperatively and after 6, 26, and 52 weeks, and annually thereafter. The mean follow-up time was 48 (range 3-91) months. Although we observed a fast recovery, including maintenance of mobility and a gradual increase in grip strength, there was a revision rate of 7/38 (24%) after 36 months, increasing to 17/38 (44%) after 72 months. The main reason for revision was loosening of the trapezial component, and biomechanical properties of the trapezial fixation may be the key problem in treating trapeziometacarpal osteoarthritis using a total prosthesis.

A biomechanical evaluation of the relative load change in the joints of the wrist with ulnar shortening: a 'handbag' model.

The wrist joint is loaded not only while applying a proximally directed load but also, less obviously, while carrying a handbag. Ulnar shortening reduces pressure and relieves pain in the ulnocarpal joint. The present study evaluated the pressure distribution in the wrist joints with ulnar shortening and lengthening when applying traction to the flexed fingers while the fingers were loaded and unloaded. The compressive forces in the loaded wrist were distributed with 67% across the radiocarpal joint and 33% across the ulnocarpal joint. Shortening the ulna by 3 mm increased load in the radius to 80%. Lengthening of the ulna by 1 mm increased its load to 55%. The load share of the distal radioulnar joint was constant even when the ulna was shortened 3-4 mm. It seems advisable to shorten the ulna by 3 mm, since the increased load in the related joints are constant within a range of -2 to -4 mm.

Non-verbal learning disabilities in children with infantile hydrocephalus, aged 4-7 years: a population-based, controlled study.

The aim of this population-based, controlled study was to investigate non-verbal learning disabilities (NLD) in children with infantile hydrocephalus (IH). For this purpose, the results from subtests measuring either assets or deficits within Rourke's model of NLD were analyzed. Children with myelomeningocele (MMC), intracranial tumors, or IQ < 70 were excluded. Of the 52 IH children included in the study, 46 were shunt-treated, whereas 6 were not shunted. The 44 controls were matched according to age, gender, and geographic variables. The Neuropsychological Assessment of Children (NEPSY) was administered to 52 children (age 4-7) with IH; (F = 17, M = 35), and to 44 controls (F = 17, M = 27). The tests used were classified along each of the dimensions "assets" or "deficits", according to Rourke's model of the elements and the dynamics of the NLD syndrome. Differences between sum scores for the subtests classified as "assets", versus "deficits" were significantly higher in the IH group as compared with the controls (p < 0.005). These findings are compatible with a higher frequency of NLD in the IH group, in which neurological confounding factors have been excluded. In addition, the model of the elements and the dynamics of the NLD syndrome may be useful when analyzing neuropsychological test results obtained with traditional and comprehensive test batteries.

Inactivation of human cells cultivated in vitro by the new mitotic inhibitors NY 4137 and NY 4138.

The effect of the two closely related drugs, the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137), and the sulfoxide 2-(2-thenyl)sulfinyl-5-bromopyrimidine (NY 4138), a sulfoxide, on the survival of cells of the human line NHIK 3025 was investigated. Cell survival was measured as the ability of single cells to form macroscopic colonies. Two-hour treatment with 0.012 mM NY 4137 resulted in 50% inactivation. The drug concentration of NY 4138 had to be adjusted about 10 times higher than that of NY 4137 for treatment periods of 2 or 24 h to obtain similar surviving fraction after treatment of asynchronous cells. Treatment of synchronized NHIK 3025 cells with NY 4137 showed that survival varied little with cell age. Following treatment with NY 4138, however, cells were particularly sensitive in G2 and in mitosis. As the survival curves for both drugs display a plateau region, where increasing the drug dose has little or no effect on cell inactivation, the presence of resistant subpopulations of cells is considered. High-performance liquid chromatography of drug solutions in cell culture medium showed that both NY 4137 and NY 4138 bound to, or were metabolized by, medium and/or cell components. The concentration of NY 4137 in cell culture medium, however, was reduced at a higher rate than NY 4138. The half-life of NY 4137 was on the order of 5 h, while the half-life of NY 4138 was over 24 h. These observations correlate well with the relative chemical reactivities for these drugs in nucleophilic displacement reactions.

Sulfhydryl-related reduction of the mitotic inhibition and cell inactivation induced by pyrimidine analogs.

Sulfhydryl-related reduction of the mitotic inhibition and cell inactivation induced by the pyrimidine analogs NY 3170, NY 4137 and NY 4138 was investigated. Human NHIK 3025 cells grown in culture were treated with the SH-compounds glutathione (GSH) and cysteine, and the S-S-compound cystine in combination with the above pyrimidine analogs. Simultaneous combination of GSH or cysteine with NY 4137 (a pyrimidine sulfone) abolished the ability of the drug to arrest cells in metaphase, while simultaneous combination of NY 4137 with cystine had no such effect. The mitigating effect of GSH and cysteine was dose-dependent and maximal at 1 mM GSH or 2.5 mM cysteine. In combination with NY 4138 (a pyrimidine sulfoxide) GSH and cysteine, but not cystine, reduced slightly the ability of NY 4138 to accumulate cells in mitosis. By contrast, neither GSH, cysteine nor cystine affected the mitotic inhibiting property of NY 3170 when in simultaneous combination with this pyrimidinone. With respect to cell inactivation, an increase in the fraction of cells surviving treatment with NY 4137 was found when GSH or cysteine, but not cystine, was simultaneously present. In order to evaluate the importance of endogenous SH-groups, we measured the effect of NY 4137 on NHIK 1922-C3 cells, a mouse-human hybrid, having a lower endogenous sulfhydryl content than NHIK 3025 cells. Treatment of these cells with NY 4137 resulted in a lower surviving fraction of cells than identical treatment of NHIK 3025 cells.

Effects of the new mitotic inhibitor pyrimidinsulfone NY 4137 on human cells in vitro and on colchicine binding to tubulin.

The effect of 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) on cells of the human line NHIK 3025 was investigated. It was shown that NY 4137 induces cell cycle specific inhibition in metaphase. A dose-dependent prolongation of metaphase was found and the fraction of cells able to escape metaphase arrest declined gradually as the concentration of NY 4137 increased. A total block in metaphase was achieved with 0.016 mM and higher concentrations of NY 4137. Interphase was also prolonged in cells treated with 0.016 mM. Inhibition of valine incorporation by NY 4137 was also found to be dose-dependent. Following a 2-h exposure to 0.2 mM NY 4137 valine incorporation was inhibited by 80-85%. Inhibition of colchicine and vincristine binding to purified tubulin was also investigated. Double reciprocal plot and gel filtration chromatography showed that NY 4137 competitively inhibited colchicine binding to DEAE-cellulose purified tubulin. NY 4137 had no effect on vincristine binding to tubulin. The binding of NY 4137 to tubulin at or near the colchicine binding site may be responsible for the metaphase arrest.