An apparently novel neurological disease clinically characterized by shaking, tremors, seizures, staggering gait, and ataxia was first observed in farmed mink kits in Denmark in 2000 and subsequently ...in Sweden, Denmark, and Finland in 2001, and again in Denmark in 2002. Lymphoplasmacytic encephalomyelitis was found in the affected kits. The lesions were most severe in the brainstem and cerebellum and consisted of neuronal degeneration and necrosis, neuronophagia, focal and diffuse gliosis, perivascular cuffs formed by lymphocytes, plasma cells and macrophages, and segmental loss of Purkinje cells. Testing was conducted to determine the cause of the disease, including general virological investigations (virus culture, negative-staining electron microscopy, immunoelectron microscopy, polymerase chain reaction for herpesviruses, adenoviruses, pestiviruses, and coronaviruses), tests for specific viral diseases (canine distemper, Borna disease, Louping ill, West Nile virus infection, tick-borne encephalitis, Aleutian disease), tests for protozoa (Toxoplasma gondii, Neospora caninum, Encephalitozoon cuniculi), bacteria (general culture, listeria, Clamydophila psittaci), and intracerebral inoculation of neonatal mice. The results of all these investigations were negative. One group of 3 mink kits inoculated intracerebrally with brain homogenate of affected mink developed clinical signs and histological lesions similar to those observed in naturally infected mink. Based on the histopathological features, it is postulated that the disease is caused by a yet unidentified virus.
There is evidence in the literature of a relationship between dose and response to adjuvant chemotherapy for breast cancer, although published results are conflicting. We therefore retrospectively ...analysed the role of dose response in patients included in four adjuvant trials of the International Breast Cancer Study Group (IBCSG, formerly the Ludwig Breast Cancer Study Group (trials I, II, III and V), all using ‘classical’ cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). A total of 1385 node-positive patients were treated with oral cyclophosphamide, and intravenous methotrexate plus 5-fluorouracil (CMF) for at least six 4 week courses. 1350 of these were included in 6 month landmark treatment outcome analyses. A total of 1029 patients were premenopausal, 321 were postmenopausal; 800 had one to three and 550 more than three involved axillary nodes at surgery. The median follow-up ranged from 12 years for trial V to 15 years for trials I–III. Patients were grouped according to three prospectively defined dose levels based on the percentage of the protocol prescribed dose that was actually administered (level I ≥85%, level II 65–84%, level III <65%). Patients who received dose level II had a higher disease-free (
P=0.07) and overall survival (
P=0.03) than those who received a higher (level I) or lower (level III) percentage. The 10 year overall survival was 60% for dose level II, 56% for dose level I, 51% for dose level III. The results were generally consistent within trial, menopausal status, and oestrogen receptor status groups. The results within nodal groups showed a large difference among the dose levels for the group with one to three positive nodes (
P=0.02), but no difference for the group with four or more positive nodes. Our results indicate that the dose–response effect remains a crucial factor in adjuvant chemotherapy of breast cancer. Reductions larger than 35% in the dose administered of oral CMF adversely influenced the outcome of breast cancer patients and should be avoided. The better outcome of the intermediate dose group indicates the need to investigate other aspects involved in the cytotoxicity of adjuvant CMF chemotherapy.
The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs.
The design of the study consists of an open, ...prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.
Patient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment. TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009). Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study. In patients without TAO, there were no differences in QoL related to mode of treatment.
The QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.
Hypercortisolism attributable to hypersecretion of ACTH by a pituitary adenoma is an uncommon and progressively lethal disease. Because of its rarity, it has been difficult to collect a large series ...of patients in order to identify the prognostic factors influencing the outcome after transsphenoidal surgery. We conducted a multicenter, retrospective analysis of the early and late results of surgical treatment of Cushing's disease. Files of patients with Cushing's disease who underwent transsphenoidal surgery between 1975 and 1990 were collected from 25 institutions throughout Europe. Data from 668 of 716 patients were suitable for statistical analyses. Surgical mortality was 1.9%, and major morbidity occurred in 97 patients (14.5%). Clinical and biochemical remission of Cushing's disease after surgery occurred in 510 cases (76.3%). Identification of the tumor by neuroradiological imaging or at operation with histopathological corroboration was associated with remission of hypercortisolism. Recurrence of the disease occurred in 65 (12.7%) of 510 patients in remission after surgery at a mean time of 39.3 months (range 6-104 months). The distribution of the recurrences did not show any apparent plateau or cluster throughout the follow-up period. Low postoperative steroid levels, absence of cortisol response to CRH, and the need for long-term glucocorticoid substitution therapy were all associated with a high probability of long-term remission. Our study demonstrates that transsphenoidal surgery is a safe and effective treatment for patients with Cushing's disease. However, after successful surgery there is a steady increase in the percentage of recurrences, which continues with time. Patients who after operation had hypoadrenocorticism and needed long-term glucocorticoid substitution therapy had the lowest risk of relapse.
Previously reported methods for the correction of tricuspid atresia involve the use of conduits and/or valves. Since many of the younger patients will outgrow their conduits and the long-term ...durability of the valve prostheses is open to question, we have devised an operation in which the right atrial (RA) appendage is anastomosed to the right ventricle (RV) with the aid of a pericardial patch. The RV, if not too hypoplastic, is used as a pumping chamber and the pulmonary valve is in its normal position. Three patients, 8, 9, and 12 years of age, were operated on with good clinical and hemodynamic results. Postoperatively, all three were acyanotic and had improved physical capacity compared with their preoperative status. The RA pressure in the first two patients 1 year after operation was 12 mm. Hg and at angiocardiography the RA-RV anastomosis was widely patent. In one of the patients, the RV was too hypoplastic to function. It should be possible to perform this operation even in younger patients and it may eliminate the need for palliative procedures and reoperations.
Sulfanilamide was chosen as a model compound in order to gain insights on the stability hierarchy of drug polymorphs from structural and thermodynamic criteria. Despite numerous studies, ...disagreements remained on the reported enthalpies associated with the mutual interconvertions of the alpha-, beta-, and gamma-forms of sulfanilamide. Therefore, the unambiguous determination of these enthalpies was the purpose of this work.
Samples, free of solvent inclusions and made of only one form, were prepared, and analyzed combining X-ray powder diffraction and Differential Scanning Calorimetry (DSC).
The enthalpy values associated with the alpha- to gamma- and beta- to gamma-transitions were found to be + 10.2 and + 10.9 J g-1, respectively. The calculated enthalpy of the beta- to alpha-transition is consistent with the experimental one (+ 1 J g-1).
The monotropy of the alpha-form was ascertained over the explored temperature range at ordinary pressure.
The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings ...of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, ...with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of depression between the two modes, there was a significant correlation between the concentration of 5-HIAA and severity of depression in the lower, but not in the upper, mode. The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.
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