Need for symptomatic management in advanced multiple sclerosis.

OBJECTIVE: A majority of patients with advanced multiple sclerosis (MS) need symptomatic treatment. Many MS-related symptoms may not be recognized and thus are not treated. We conducted a study to estimate the prevalence of inadequate symptomatic treatment of patients with advanced MS. METHODS: Patients with advanced MS admitted to a specialist MS rehabilitation clinic were included in this study. Severity was assessed using the Expanded Disability Status Scale (EDSS). The information we collected included age of onset, initial course, time to sustained disability, pharmacological treatment, degree of spasticity, pain and bladder dysfunction, and unmet needs of symptomatic treatment. RESULTS: In total, we assessed demographic and clinical characteristics in 129 patients with a mean age of 56 years and a median EDSS of 7.5. The proportion with inadequate symptom treatment was regarding spasticity 46%, pain 28%, and bladder dysfunction 23%. DISCUSSION: This study showed that a large proportion of patients with advanced MS had lack of symptomatic treatment. These patients probably underuse neurological specialist services. Better symptomatic treatment could contribute to improving quality of life of people with MS.

Survival over 12 years following acute stroke: initial treatment in a stroke unit vs general medical wards.

BACKGROUND: Few studies have assessed the influence of the organization of stroke care on long-term survival. AIMS OF THE STUDY: To compare survival over 12 years after stroke between subjects treated in an acute stroke unit (SU) and those treated in general medical wards (GMW). METHODS: In total, 550 subjects ≥60 years of age with acute stroke were prospectively allocated according to date of birth (day of the month) to treatment in a SU with relatively short length of stay or GMWs. We assessed survival through a link to the register of Statistics Norway. Groups were compared using Kaplan-Meier analysis on an intention-to-treat basis. RESULTS: Of the 550 eligible subjects, 271 were allocated to a SU and 279 to GMWs. There still was no difference in mortality over 12 years between the groups (P = 0.15, log-rank test) CONCLUSIONS: An acute SU offering early treatment and rehabilitation did not offer better long-term mortality after stroke in patients ≥60 years old than initial treatment in GMWs.

Activation of the ribosomal DNA promoter in cells exposed to insulinlike growth factor I.

We constructed a stable cell line, 3T3A5, which carried a chimeric gene in which the simian virus 40 T-antigen-coding gene was under the control of the mouse ribosomal DNA promoter. These cells expressed T antigen when they were growing exponentially in 10% fetal calf serum, but they all became T negative when incubated for 5 days in low-concentration serum. The readdition of serum or platelet-poor plasma again induced the expression of T antigen, which was accompanied by an increase in steady-state levels of the corresponding RNA. Among the various growth factors tested for their ability to induce T-antigen expression in 3T3A5 cells, only insulinlike growth factor I (IGF-I) could induce T antigen at physiological concentrations. The effect of IGF-I or platelet-poor plasma was abolished by an antibody to IGF-I. Other growth factors, like insulin and epidermal growth factor, could induce the expression of T antigen in 3T3A5 cells, but only at concentrations far above the physiological range. Other growth factors were totally ineffective. These results indicate that exposure of cells to IGF-I can activate transcription from the ribosomal DNA promoter.

4,6-Benzylidene-D-glucose, a benzaldehyde derivative that inhibits protein synthesis but not mitosis of NHIK 3025 cells.

The effect of the benzaldehyde derivative 4,6-benzylidene-D-glucose (BG) on cell-cycle kinetics, protein synthesis, and cell survival of human NHIK 3025 cells has been investigated. The effects are compared with results reported previously for benzaldehyde, which was shown to inhibit protein synthesis as well as induce metaphase inhibition. BG exerted an effect on protein synthesis similar to that of benzaldehyde, but did not affect metaphase. Inhibition of protein synthesis was measured as a reduction in the rate of incorporation of [3H]valine and is thus a measure of the rate of total protein synthesis. The quantitative effect on the rate of protein synthesis was equal for the two drugs when compared on a concentration basis. Both drugs induced inhibition of cell-cycle progression during interphase, which is thought to be a secondary result of the protein synthesis inhibition. The concentration of BG and the hydrolysis product benzaldehyde were determined in cell culture medium by high-performance liquid chromatography. BG was not found to be hydrolyzed to free benzaldehyde when in contact with cells or in a cell sonicate. The results indicate that BG is not metabolized but acts in the form of BG.

Regulation of protein metabolism of human cells during and after acute hypoxia.

Protein synthesis and protein degradation were measured in human NHIK 3025 cells cultured in vitro during and after an acute treatment of extreme hypoxia (less than 4 ppm O2). Furthermore, total protein content per cell was recorded and related to cell cycle phase by coincident measurement of DNA and protein using two-parametric flow cytometry. During hypoxia protein synthesis was reduced and protein degradation was increased, resulting in no net accumulation of protein. From the flow cytometric recordings, the amount of protein per cell was found to be constant, or perhaps in some of the cells slightly reduced, after a 3-h period of extreme hypoxia. Three h after reaeration protein degradation had returned to normal while protein synthesis was slightly above normal. The flow cytometric recordings showed that after reaeration the protein accumulation was particularly high in the subpopulation of cells which accumulated at the G1-S border during hypoxia and entered S phase as a partly synchronized subpopulation after reaeration. Since we know from our earlier studies that these cells are more resistant to hypoxia than cells in S phase we conclude that this high protein accumulation may be important in restoring a pool of proteins which initiate DNA synthesis and perhaps other proteins of importance to cell growth.

Survival of unselected stroke patients in a stroke unit compared with conventional care.

BACKGROUND: Recent meta-analyses have reported a beneficial effect of stroke units compared with traditional care, both on patient survival and on dependency after one year. AIM: To determine whether these results can be reproduced outside a clinical trial setting. SETTING: A medium-sized general hospital. METHODS: From 1993 to 1998, all patients aged >60 years with suspected acute stroke were allocated either to a stroke unit or general medical wards according to date of birth (day of the month). Patients were identified retrospectively, using a discharge diagnosis of ICD-9 codes 431, 434 and 436. We assessed 30-day and 1-year survival. RESULTS: In the stroke unit, 926/1128 patients survived at 30 days, vs. 905/1141 in the general medical wards (p=0.08). Beyond the first 30 days, there was no difference in survival (p=0.27). Under Cox regression analysis, there was a 20% reduction in mortality in the stroke unit after 30 days compared with the general medical wards (RR 0.80, p=0.02) after adjusting for age, gender, stroke type and season of the year. DISCUSSION: In this, the largest single-centre study to evaluate the survival benefit of a stroke unit, survival at 30 days was increased, although not significantly so. Survival at one year was unchanged.

Growth hormone and insulin-like growth factor I receptors in the temporomandibular joint of the rat.

While there are numerous investigations on hormonal control of long bone epiphyseal growth, corresponding knowledge is sparse concerning the condylar cartilage. We investigated the distribution of growth hormone (GH) and insulin-like growth factor I (IGF-I) receptors in the temporomandibular joint (TMJ), especially the condyle, and compared the findings with information of long bone epiphyseal plates. The localization of the receptors was examined in vivo by immunohistochemical methods in one- to 21-day-old rats. GH receptors were detected in various components of the TMJ, but not in the fibrous articular surface or in the cartilage layers of the condyle. IGF-I receptors were found in the fibrous articular surface of the condyle and particularly in the superior and posterosuperior regions of the condylar cartilage, the depth of the labeled cell layer increasing significantly with age. It is evident that the expression of GH and IGF-I receptors is area-specific in the TMJ. Early post-natal growth and development of the mandibular condylar cartilage seem to be IGF-I-dependent but not directly dependent on GH.

Morphogenic potential of autogenous costal cartilage transplanted into the interparietal suture area of the rat.

A study was carried out to determine the separability of costochondral tissue and to investigate the preservation of its integrity as a transplant to a relatively immobile osseous site. On 10-day-old rats, two autogenous rib sections, complete with bone and cartilage, were transplanted across the interparietal suture with the cartilaginous ends either in the same direction or in opposite directions; untreated rats were used as controls. The animals, injected with Alizarin red S, were killed 25, 50, and 75 days after the operation, 10 at each time. At 25 days after the operation the calvarial width and neurocranial height were significantly greater, and the strip of new white bone appeared wider in the experimental animals as compared to the untreated control rats; later, the differences were less pronounced. The changes in the neurocranial morphology seemed more symmetrical following positioning of the cartilaginous ends of the graft in opposite directions than when they were in the same direction. In some transplants the endochondral ossification process appeared normal at the termination of the experimental period, but signs of degeneration were also observed. The findings were considered to indicate that costochondral transplants are endowed with an intrinsic tissue-separating capacity, and that they can preserve their integrity for an extended period under relatively nonfunctional conditions.

Disturbances in craniofacial morphology in children treated for solid tumors.

Because of increased survival rates in childhood cancer, special interest has been focused on the side-effects of the therapy and the quality of life in long-term survivors. Our aim was to investigate craniofacial growth in children who had received different kinds of antineoplastic therapies for solid tumors. A total of 40 children treated in the Turku University Central Hospital were examined and divided into three different groups. Group 1 comprised 18 children treated for intracranial tumors with cranial irradiation (CRI) and chemotherapy (CT) including alkylating agents. Seven children out of 18 in this group received growth hormone (GH) therapy. In Group 2, 11 children with extracranial solid tumors also received multiagent CT including alkylating agents, but no CRI. Group 3 consisted of 11 children treated for Wilm's tumor with CT, which did not include alkylating agents or CRI. A total of 19 linear and four angular variables from the lateral cephalograms of the subjects were measured. Most deviations in craniofacial structures were found in children treated with combined CRI and multiagent CT. All disturbances were seen in the vertical measurements which were reduced when compared to the matched controls. It seems reasonable to assume that impaired growth following combined radio- and chemotherapy, as well as GH treatment, particularly affects cartilage-mediated growth. However, the deviations seen in the present study were fairly minor and did not usually require clinical consideration.

Growth potential of the rat mandibular condyle as an isogeneic transplant traversing the interparietal suture.

The mandibular condyle of 5-, 10- or 20-day inbred male rats was transplanted across the interparietal suture of male litter-mates and the transverse dimension of the neurocranium was measured from dry skulls at 25 or 35 days. The width of the neurocranium had increased significantly from days 5 or 10 to 25 in the rats with the transplants, whereas the difference from controls was small or non-existent by 35 days. Histological examination showed that the cartilaginous zone was reduced in the transplants at 25 days but that there were still layers of chondrocytes at 35 days. It is suggested that the rat mandibular condyle is endowed with a tissue-separating, interstitial growth potential that, to some extent, is unrelated to mobility, and essentially effected by chondrocyte hypertrophy.

Morphogenetic potential of rat growth cartilages as isogeneic transplants in the interparietal suture area.

The proximal end of the tibia or the spheno-occipital synchondrosis with some adjoining bone were isogeneically transplanted across the interparietal suture of 10-day-old rats. As a sham procedure, a piece of calvarium traversed by a part of the interparietal suture was interchanged between pairs of animals. Untreated rats served as controls. The animals, injected with Alizarin red S, were killed 25-75 days after the operation, 10 in each group. The transverse dimensions of the neurocranium were larger in the rats with the cartilage transplants than in the controls, particularly at 25 days after the operation; the differences persisted longer in the animals with the synchondroseal transplant. The orientation of the bone interdigitation at the anterior lambdoidal suture changed temporarily in response to the excessive lateral displacement of the parietal bones. The observations indicate that basicranial synchondroses, like epiphyseal cartilage, are endowed with a tissue-separating property that may persist for a prolonged period under transplant conditions. As such cartilaginous structures may also be affected by environmental influences, there must be a two-way interaction between the synchondroses and their immediate environment.

Distribution of insulin-like growth factor-I mRNA in the mandibular condyle and rib cartilage of the rat during growth.

This study makes a molecular biological comparison of primary and secondary cartilage at an early phase of postnatal development. The distribution of insulin-like growth factor-I (IGF-I) mRNA expression in the mandibular condyle and rib cartilage of 1-28-day-old rats was examined after in situ hybridisation using an oligo probe cocktail for IGF-I mRNA. In the condyle, expression was localised to a narrow strip under the articular layer where the cells are undifferentiated. Essentially, no differences were found in IGF-I synthesis within three samples from the same age group or between different age groups. In rib cartilage, IGF-I mRNA was localised within the germinative, proliferative and early hypertrophic cell layers in 1-28-day-old rats. Again, there were no differences in expression among animals of the same age or as a function of age. This pattern of IGF-I mRNA expression indicates that IGF-I synthesis during growth of the mandibular condylar cartilage is different from that of costal cartilage. The findings shed light on the problem of overgrowth often associated with the use of costochondral grafts to replace defective mandibular condyles.

An ELISA-method using magnetic beads as solid phase for rapid quantitation of mouse and human immunoglobulins.

This work describes an ELISA-method using superparamagnetic polystyrene beads (Dynabeads M-450) as solid phase, that may be used to measure the concentration of immunoglobulins in various fluids. The immunoglobulin was captured between beads coated with either rabbit, goat or sheep antibodies and the same antibody conjugated to horseradish peroxidase. The method has been used to quantitate mouse and human immunoglobulins in cell culture supernatants. Due to the rapid binding kinetics between the beads and the soluble antigen (immunoglobulin), each incubation takes only ten minutes, allowing the whole assay to be performed within one hour.

Very long-term mortality after ischemic stroke: predictors of cardiovascular death.

BACKGROUND: The purpose of this article is to find possible predictors associated with long-term mortality and long-term cardiovascular death after stroke. METHODS: A cohort of 550 patients with acute stroke admitted to a single hospital within 24 h of a stroke were recruited consecutively. Patients were followed for 12 years or until death. Information on death was collected through linkage with the National Population Register of Statistics Norway, an official register containing name, date of birth, address, and date of death, and the National Register of Cause of Death. Cardiovascular deaths were defined as ICD 9 codes 390 to 448 and ICD 10 codes I00 to I99. RESULTS: The proportion of cardiovascular deaths was 71%. In multivariate Cox regression analysis of cardiovascular mortality, stroke severity (HR 2.78; 95% CI 2.13-3.57), hemorrhagic stroke (2.0; 1.43-2.78), diabetes (1.85; 1.37-2.50), male gender (1.69; 1.31-2.17), ischemic heart disease (1.56; 1.16-2.13), age (1.06; 1.04-1.08), and right hemispheric stroke (1.49; 1.16-1.89) were significant predictors. DISCUSSION: This study shows that age, male gender, stroke severity, hemorrhagic stroke, diabetes, ischemic heart disease, and right hemispheric stroke are predictors associated with increased risk of long-term cardiovascular mortality. Neither atrial fibrillation, antihypertensive treatment on admission, smoking, or living alone was risk factors for late cardiovascular deaths.

Delirium in acute stroke--prevalence and risk factors.

BACKGROUND: Delirium is frequently seen as a major complication among elderly stroke patients. Few studies have prospectively studied delirium as a complication of acute stroke. In these studies, the results are conflicting regarding risk factors and estimated prevalence. The aims of the present study are to assess the prevalence of delirium in patients with acute stroke treated in an acute Stroke Unit, identify characteristics of patients with delirium and important factors associated with the development of delirium. METHODS: We conducted a prospective study of patients with delirium and acute stroke consecutively admitted to a Stroke Unit. The diagnosis of delirium was based on Confusion Assessment Method (CAM). CAM is devised from DSM-III-R criteria based on the diagnosis of delirium, and is a simple test with high sensitivity and specificity. RESULTS: One hundred and seventy-eight patients with a diagnosis of stroke were eligible for the study. The prevalence of delirium in acute stroke in our study was 10% (18 of 178 patients). Patients with delirium had significantly longer length of stay in the Stroke Unit (12.3 vs 8.5 days, P < 0.004). Prestroke dementia [odds ratio (OR) 18.7], hemianopsia (OR 12.3), apraxia (OR 11.0), higher age (OR 5.5) and infection (UTI or pneumonia) (OR 4.9) during in-hospital stay were associated with increased risk of delirium. CONCLUSION: One of 10 stroke patients had delirium. This is the lowest prevalence of delirium shown in acute stroke patients. In our study, all patients were treated in a Stroke Unit. A Stroke Unit like the Scandinavian model may be beneficial in preventing delirium.