Efficacy of interventions with caregivers: a reanalysis

This paper presents a reanalysis of data from a previously reported study with family caregivers of dementia patients using the method of prediction analysis. Compared with subjects on a waiting list or enrolled in support groups, caregivers in individual and family counseling were more likely to have successful outcomes on all dependent measures (Brief Symptom Inventory, personal strain, and role strain).     

The Balgrist Reference Center for Mesenchymal Tumors. The significance of a clinico-pathological tumor register

Compared to other forms of cancer, malignant mesenchymal tumors are rare: individual surgeons see few such patients and do not usually treat them personally. The radiologic and histologic problems of differential diagnosis, and the subtle distinction between benign and malignant make decision an onerous task for surgeons, orthopedists, pathologists, oncologists and radiotherapists. For this reason referral centers should enable oncologic working groups to confirm diagnoses, establish appropriate therapeutic schedules, and to help in follow-up patient care. Around 1970, a center was created at Balgrist University Orthopedic Clinic for the gathering, documentation and coordination of clinical and pathological data from patients with tumors and tumorous lesions of the skeleton and soft tissues. Subsequently, a circle of continuously collaborating specialists, including some from other institutions, formed about the register. The viability of the reference center is assured by unequivocal morphologic diagnosis; presence of the pathologist during the planning and procedure of the biopsy and other tumor-related interventions in the operating room; clinical investigations including the immediate availability of diagnostic procedures; charting all clinical data; and the clinic's follow-up of its own patients. Fully integrated in the Orthopedic Clinic and Polyclinic, the register is a major instrument in the treatment of patients at risk with tumor. Given the diversity of clinicopathological presentation, the register permits direct access to analogous situations in individual cases.     

Renal allograft immunosuppression: II. A randomized trial of withdrawal of one drug in triple drug immunosuppression

Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal.     

The effect of ionic strength on the kinetics of rigor development in skinned fast-twitch skeletal muscle fibres

 Recent atomic 3-D reconstructions of the acto-myosin interface suggest that electrostatic interactions are important in the initial phase of cross-bridge formation. Earlier biochemical studies had also given strong evidence for the ionic strength dependence of this step in the cross-bridge cycle. We have probed these interactions by altering the ionic strength (Γ/2) of the medium mainly with K⁺, imidazole⁺ and EGTA^2– to vary charge shielding. We examined the effect of ionic strength on the kinetics of rigor development at low Ca²⁺ (experimental temperature 18–22°C) in chemically skinned single fast-twitch fibres of mouse extensor digitorum longus (EDL) muscle. On average the delay before rigor onset was 10 times longer, the maximum rate of rigor tension development was 10 times slower, the steady-state rigor tension was 3 times lower and the in-phase stiffness was 2 times lower at high (230 mM) compared to low (60 mM) ionic strength. These results were modelled by calculating ATP depletion in the fibre due to diffusional loss of ATP and acto-myosin Mg.ATPase activity. The difference in delay before rigor onset at low and high ionic strength could be explained in our model by assuming a 15 times higher Mg.ATPase activity and a threefold increase in K _m in relaxing conditions at low ionic strength. Activation by Ca²⁺ induced at different time points before and during onset of rigor confirmed the calculated time course of ATP depletion. We have also investigated ionic strength effects on rigor development with the activated troponin/tropomyosin complex. ATP withdrawl at maximum activation by Ca²⁺ induced force transients which led into a ”high rigor” state. The peak forces of these force transients were very similar at low and high ionic strength. The subsequent decrease in tension was only 10% slower and steady-state ”high rigor” tension was reduced by only 27% at high compared to low ionic strength. Addition of 10 mM phosphate to lower cross-bridge attachment strongly suppressed the transient increases in force at high ionic strength and reduced the steady-state rigor tension by 17%. A qualitatively similar but smaller effect of phosphate was observed at low ionic strength where steady-state rigor force was reduced by 10%. The data presented in this study show a very strong effect of ionic strength on rigor development in relaxed fibres whereas the ionic strength dependence of rigor development after thin filament activation was much less. The data confirm the importance of electrostatic interactions in cross-bridge attachment and cross-bridge-attachment-induced activation of thin filaments. Received: 3 September 1997 / Received after revision and accepted: 12 December 1997     

Bacterial colonization and infection in an intensive care unit

One hundred and one patients, nursed in an intensive care unit for at least 24h, were monitored for bacterial colonization and infection. The infection rates were similar to those in other reports. Patients were not generally colonized with common environmental strains in the unit. Bacterial dissemination between patients was uncommon. No gentamicin resistant gram negative or Staphylococcus aureus strains were observed, nor methicillin resistant Staphylococcus aureus strains. the hypothesis that these favourable conditions are partly related to the excellent isolation and barrier nursing facilities in the unit cannot be fully substantiated.     

Neue Entwicklungen in der systemischen Psoriasistherapie

The current standard systemic therapeutic modalities for psoriasis have many potential side effects. Progress made in the understanding of the pathophysiology of psoriasis as a T‐cell‐mediated dermatosis provide options for new more precise therapeutic approaches. These immunological therapeutic strategies involve the inhibition/depletion of activated T‐lymphocytes, the inhibition of antigen presentation and thus the regulation of T‐cell activation, the inhibition of adhesion of inflammatory cells, the inhibition of effects of proinflammatory mediators and the administration of antiinflammatory cytokines. This article summarizes these new systemic therapeutic approaches. Clinical results in the early studies have been mixed. In the next years further results of phase II‐ and phase III‐studies may be expected, which should allow better assessment of the potential of those particular approaches. Some of these approaches could lead to the approval of new drugs to treat psoriasis and to enhance or replace already existing therapeutic options. Furthermore results of therapeutic experiments should contribute to a better understanding of the disease. As we learn which mechanisms are more or less important for the disease, we will be better able to plan intervention strategies.     

Acute fatal myeloencephalopathy after combined intrathecal chemotherapy in a child with acute lymphoblastic leukemia

We report a case of a fatal toxic encephalomyelopathy in a 12-year-old girl due to prophylactic intrathecal injection of methotrexate and cytosine arabinoside, with a characteristic progressive symptomatology leading to death after 28 days. The location and type of neuropathological changes support the hypothesis of a direct toxic effect of methotrexate and/or cytosine arabinoside on structures directly exposed to the cerebrospinal fluid.