Poststroke fatigue: the patient perspective.

PURPOSE: Fatigue is reported as a prevalent symptom post stroke. The purpose of this study is to explore the patent perspective of this symptom, how it is experienced, and its subjective impact on the patient. METHOD: The qualitative procedure of interpretative phenomenological analysis (IPA) was used to analyze the narratives of 10 subjects with previous stroke, who each undertook a single, semi-structured interview. RESULTS: Fatigue was a salient symptom for all the patients. Six main themes were identified. Tiredness/sleep was recognized in all the narratives, and themes of restriction, frustration, and determination/coping reflected varying degrees of physical, cognitive, and psychological dimensions to fatigue. Depression/motivation was also identified, reflecting low mood and helplessness. The remaining theme support indicated a social dimension, with patients recognizing the need for professional and familial support. Further subthemes were identified, and the thematic descriptions of the physical and psychosocial aspects indicated the complexity of fatigue and unique patient profiles. A holistic overview of each narrative furthered an understanding of the dynamic interrelationships between these aspects and their impact on the patient. There were prevalent patterns, but these were different for each patient. CONCLUSION: A better understanding of the varied dimensions or themes elaborated for poststroke fatigue, and their interrelationships, should help in mitigating its impact. The analysis cautions against giving any simplistic and unitary advice to patients about dealing with fatigue.

MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T cell responses.

Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favours pro- or anti-inflammatory CD4+ T cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4+ T cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4+ T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4+ T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4+ T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen presenting cells and that IEC MHC II expression fine-tunes local effector CD4+ T cell responses during intestinal inflammation.

Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum.

The soluble granule chymase, rat mast cell protease-II (RMCP-II), is abundantly expressed in intestinal mucosal mast cells (MMC) but its function is not known. One hypothesis is that RMCP-II degrades the epithelial basement membrane and promotes the loss of enterocytes typically associated with type I hypersensitivity reactions in the rat. To test this hypothesis more directly, ex vivo perfusion of the cranial mesenteric artery and jejunal lumen was used to monitor the anaphylactic release of RMCP-II and its effects on mucosal permeability and epithelial integrity. Within 2 min of intravascular challenge with soluble adult Nippostrongylus brasiliensis worm antigen there was a 1,000-fold (P < 0.02) increase in the concentration of RMCP-II in the vascular perfusate from the jejunum of Nippostrongylus-sensitized rats but not the controls. Similarly, translocation of RMCP-II into the gut lumen increased 10-fold (P < 0.02) after 2 min only in worm antigen-challenged immune rats. Using an identical protocol, but incorporating Evans blue-labeled human serum albumin (EB-HSA) in the vascular perfusate, the timing of the release of RMCP-II into the two compartments was very similar to the first experiment and furthermore the translocation of EB-HSA increased 18-fold (P < 0.05) after 4 min in sensitized rats challenged with worm antigen. To examine the effects of RMCP-II more directly 1 mg of the highly purified chymase was introduced into the cranial mesenteric artery in ex vivo perfused normal rats. A significant (P < 0.05) 70-fold increase in concentration of RMCP-II in jejunal perfusate occurred after 6 min. In a repeat dose-response experiment, infusion of 0.375, 0.75, or 1.5 mg of RMCP-II, together with EB-HSA, established that the cumulative amounts of RMCP-II and EB-HSA translocated from the vasculature to the gut lumen in each perfusion (during the 10-min period of RMCP-II infusion) were significantly correlated. Analysis of intestinal perfusates by SDS-PAGE and by Western blotting using monoclonal anti-RMCP-II antibody confirmed that there was a concomitant translocation of both the protease and EB-HSA into the gut lumen. Histological evaluation of the mucosa failed to reveal any significant morphological change in any of the experiments. The rapid development of macromolecular leak, its association with the translocation of RMCP-II, and the absence of gross epithelial lesions, suggest for the first time that a mast cell granule chymase increases epithelial permeability via a paracellular route and implies that the substrate may be a protein, or proteins, in the epithelial junctional complex.

Thermodiffusional transport in pelagic clay: implications for nuclear waste disposal in geological media.

Thermal gradient experiments in sediment-seawater systems revealed large-scale fluxes of aqueous electrolytic components away from the heat source through thermal diffusion. These findings indicate a need for similar studies in other geological materials of low permeability in order to assess the implications of this phenomenon for various nuclear waste disposal options.

Incidence and risk factors for alopecia in survivors of critical illness: A multi-centre observational study.

PURPOSE: To investigate the incidence, nature and risk factors for patient-reported alopecia in survivors of critical illness. MATERIALS AND METHODS: A multi-centre, mixed methods observational study in the intensive care units (ICU) of ten hospitals in Wales. All patients with an ICU stay of 5 days or more, able to give consent were included. Demographic variables and risk factors were collected. A pre-designed survey was completed at three months post-ICU discharge. Statistical analysis included numbers and percentages (categorical variables) and medians and interquartile ranges (continuous variables). Comparisons between patients with and without alopecia were made using Fisher's Exact test (categorical variables) and Mann Whitney U test (continuous variables). Multivariate logistic regression analysis was used to determine the risk factors for alopecia. RESULTS: The survey was completed by 123 patients with alopecia reported in 44 (36%) patients. The only risk factor for alopecia on analysis was sepsis / septic shock (p < .001; OR: 5.1, 95%CI: 2.1-12.4). CONCLUSIONS: Limited research exists examining the incidence, nature and risk factors for patient-reported alopecia in adult survivors of critical illness. The results of this study highlight the need to discuss the potential for alopecia with survivors of critical illness, who had sepsis / septic shock.

A randomized group intervention trial to enhance mood and self-efficacy in people with multiple sclerosis.

OBJECTIVES: To document mood, self-efficacy, and resiliency in people with multiple sclerosis (MS) following a brief group psychological intervention, and to examine whether benefits were greater than those derived from provision of education or group social interaction. DESIGN: A randomized controlled intervention trial assessing outcomes at five time points over a 1-year follow-up. METHODS: Participants with MS were assigned to one of three groups: one receiving brief group psychological intervention (PG) comprising three 90 minute cognitive behavioural sessions supported by an Information Booklet dealing with mental and emotional issues relating to MS; a group provided only with educational material - the information booklet group (IBG); and a group who not only received the booklet but also participated in non-structured social discussion (SDG) sessions similar in length and number to PG participants. Outcomes were documented using questionnaires. RESULTS: Outcomes were assessed using area under the curve (AUC) analysis: a summary measure that considers individual changes serially over time to provide a more meaningful picture than the one based on single time points. Ninety participants were followed up over the 12-month post-intervention, and their data are included in the analysis. Analyses indicated benefits in all outcome dimensions for the psychotherapeutic (PG) and social discussion groups (SDG) relative to the IBG group, but no differences between PG and SDG. CONCLUSION: The study indicates benefits from psychosocial intervention compared with bibliotherapy, with some additional benefit from psychological intervention compared with a social discussion group. Results suggest that much of the benefit may derive from non-specific therapeutic components. Without psychosocial intervention, the psychological status of people with MS worsened over time.

Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution.

Crystals of monosodium urate (MSU) provide a dose-dependent stimulus for the production by human blood monocytes of tumor necrosis factor (TNF), a cytokine with proinflammatory properties; TNF activity was inhibited selectively by monoclonal antibody to TNF alpha. Biologically active cell-associated TNF activity peaked at 3 h and was exceeded at 6 h by extracellular activity, which peaked at 12-18 h. Comparable kinetics were observed with immunoreactive TNF alpha. TNF alpha mRNA accumulation in monocytes stimulated with MSU crystals appeared as a single peak at 2-4 h, kinetics compatible with rapid production of a short half-life transcript. In contrast, crystals of calcium pyrophosphate or of hydroxyapatite did not stimulate significant production of TNF or of message. Fresh tophaceous material from a patient with gout contained significant levels of TNF alpha and cells cultured from the tophus produced TNF alpha in vitro. In rheumatoid synovial cells, spontaneous release of TNF alpha was increased by in vitro exposure to MSU crystals. Taken together with earlier work, these results support an expanded view of gouty inflammation in which the crystal-stimulated production of cytokines provides a crucial link between crystal deposition and many of the clinical and pathological facts of both acute and chronic gouty arthritis.

Facilitation of Vaginal Delivery in an Infant with Complete Heart Block Secondary to Maternal Anti-Ro Antibodies.

Congenital heart block (CHB) is a rare disorder that may be associated with a high morbidity and even mortality, with a risk of death both in utero and during infancy. Women with serum titres of anti-Ro and/or anti-La antibodies carry a risk of CHB of 1-5% in their offspring, with a recurrence risk of approximately 20%. We present a case of a 36-year-old female with a pregnancy complicated by congenital heart block. Autoimmune profiling at booking showed she was positive for lupus anticoagulant and anti-Ro antibodies. A fetal echocardiogram at 21 + 3 showed complete heart block. She was monitored throughout the remainder of her pregnancy with serial growth scans, cardiovascular profiling, and BPP scoring. She had a normal vaginal delivery at term to a female infant.

Hemolytic transfusion reactions in oncology patients: experience in a large cancer center.

At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, the incidence of hemolytic transfusion reactions over an eight-year period (1974-1981) was analyzed. Only four hemolytic transfusion reactions were reported out of 142,957 transfusions of blood (a frequency of one reaction in 35,739.25 transfusions). This could be due to the following factors: (1) Impairment of immune status related to the malignant process or temporary immunosuppression caused by intensive chemotherapy could enable patients to tolerate incompatible transfusions. (2) The reactions are overlooked or masked by the severity of disease in cancer patients in spite of an elaborate education for nurses, residents/fellows, and staff physicians about the dangers of hemolytic reactions. The figures herein reported are lower than those reported from non-oncology hospital settings.

Sequelae of left ventricular electrical endocardial ablation.

The endomyocardial residual effects of left ventricular endocardial electrical ablation utilizing unipolar and bipolar electrode catheters were studied in 15 dogs. Histopathologic techniques specific for contraction band necrosis revealed that the mean maximal depth and breadth of necrosis was 0.63 +/- 0.44 and 1.23 +/- 0.82 cm, respectively. The dimensions of necrosis were significantly increased when utilizing larger energy discharges, especially through unipolar electrodes. Four dogs died during the procedure, three from ventricular fibrillation and one from asystole, and two died suddenly within the succeeding 24 hours. Endocardial thrombi were noted at necropsy in two dogs. In conclusion, transcatheter endocardial electrical ablation may destroy a sufficient mass of myocardium to interrupt arrhythmogenic conduction tissue, especially when larger currents are delivered through unipolar electrodes. However, serious ventricular arrhythmias and endocardial thrombi should be anticipated.

The Managed Military Health System for Force Generation-project.

In summary, the Managed Military Health System for Force Generation will: Allow better understanding of health issues and illness patterns in the Armed Forces. Ensure optimum health and medical fitness of service personnel throughout their military careers by: Promoting health. Protecting health. Providing timely, properly co-ordinated, healthcare from military and civilian providers. In conjunction with DMICP, provide a seamless system of patient care and administration involving all healthcare providers. Enable all military personnel to make good health decisions. Ensure a smooth transition to NHS care on completion of Service. Improve the morale of those in the Defence Medical Services through working in a high quality organisation.

Comparison of gastrointestinal blood loss in healthy male volunteers during repeated administration of standard and sustained action tiaprofenic acid and sustained release indomethacin.

Gastrointestinal blood loss was measured in 30 healthy male volunteers before and during 4 weeks of oral treatment with either tiaprofenic acid tablets 300 mg twice daily, tiaprofenic acid sustained action (SA) capsules 600 mg once daily, or indomethacin sustained release (SR) capsules 75 mg once daily, in an open parallel-group study of 38 days' duration. Autologous erythrocytes labelled with 51Cr were given intravenously on the first study day. Gastrointestinal blood loss was measured by comparing faecal and red blood cell 51Cr activity during the second and fourth weeks of drug treatment. Blood loss was significantly greater during treatment with all 3 active preparations than during the pretreatment period, but this comparison is of limited value because placebo was not given in parallel and because in 4 subjects, who had to have their erythrocytes relabelled, there was no pretreatment data. The tiaprofenic acid SA group had consistently lower blood loss than the tiaprofenic acid tablet group. Both these groups also had consistently lower blood loss than the indomethacin SR group, although the difference between the treatment groups was not significant. Blood loss during the fourth week of treatment was less than during the second week of treatment for both the tiaprofenic acid SA and indomethacin SR capsule groups. With tiaprofenic acid tablets, blood loss was very similar at weeks 2 and 4 but this result should be viewed with caution because data at week 2 were missing for 3 subjects. Thus, formulation of tiaprofenic acid as a sustained action capsule does not appear to increase gastric irritancy as measured by faecal blood loss.

Increased immobility in an automated forced swimming test following lesion of the habenula in rats: absence of evidence for a contribution from motor impairment.

The effects of lesions of the habenula on responses during a forced swimming test (FST) were examined. Active behavior, documented by turns on a drum immersed in a water tank, were reduced in lesioned rats. Lesioned rats also demonstrated an inability to escape from the water by climbing onto the drum when it was locked in position at the end of the test. There was a tendency for lesioned rats to show more activity in open-field tests either after the FST or independent of such prior testing. Lesioned rats showed no motor or postural abnormalities and were able to maintain position for longer than controls during a rotating rod test. Collectively, the results are compatible with the suggestion that lesions of the habenula impair the ability to change motor strategies under stress but indicate such failures may not be ascribed to gross motor impairment.

Dissociation of behavioral changes in rats resulting from lesions of the habenula versus fasciculus retroflexus and their possible anatomical substrates.

Lesions in either the habenula or its primary efferent pathway, the fasciculus retroflexus (FR), impaired avoidance responding. However, lesions of only the FR provided a persistent elevation of locomotor activity. Immunocytochemical study of the interpeduncular nucleus (IPN) through injection of retrograde tracers into the IPN and the overlying ventral tegmental area indicated that habenular lesions spared both rostral habenula and forebrain projections to the caudal midbrain, but these projections were axotomized by FR lesions. Rostral sparing of the habenula resulted in normal peptidergic staining in the IPN, and normal cholinergic innervation was absent. Performance of individual rats in behavioral tests was consistent with variations in anatomical sparing. Such considerations may account for previous discrepancies in functional effects of habenular lesions.

Evidence for the role of serotonin in the inhibition of specific motor responses.

Two behavioural paradigms were used to test the effects of serotonin depletion on a specific form of response inhibition. Treatment with both p-chlorophenylalanine (p-CPA) at 200 mg/kg and lesions of the medial raphe nucleus impaired the acquisition of a step-off passive-avoidance response. The experimental design allowed the elimination of alternative interpretations in terms of increased sensitivity to shock and increased responsiveness to stimuli. p-CPA also impaired response inhibition during an omission-training schedule. The results of the three studies support a general role of serotonin in withholding specific instrumental (reinforced) motor actions. The results contrast with those of studies supporting a role of noradrenaline in response inhibition. A tentative conclusion supports Konorski's (1967) suggestion for differentiation of various types of response inhibition that are mediated by different neurochemical systems.

Attenuated response to nomifensine in rats during a swim test following lesion of the habenula complex.

Male Lister rats with bilateral lesions of the habenula nuclei were observed during two consecutive phases of a swim test. During the first phase of the test, when escape was not possible, lesioned animals demonstrated fewer changes of behaviour. Lesioned animals failed to utilise an introduced external cue and escape route in the second part of the test. Control rats treated with the antidepressant nomifensine showed few changes of behaviour during the inescapable phase of the test but an enhanced ability to escape. Nomifensine produced no improvement of escape behaviour in lesioned animals, suggesting that this behavioural effect of nomifensine in controls is dependent on the habenula relay. The data also suggest that more than one response in swim tests can serve as an index of depression.

Classification of human and animal strains of Fusobacterium necrophorum by their pathogenic effects in mice.

Forty-six strains of Fusobacterium necrophorum, 24 from animals and 22 of human origin, were examined by pathogenicity tests in mice, while the same strains were being examined in laboratories elsewhere by other methods. The pathogenicity tests consisted of (1) subcutaneous inoculation with a large dose of a pure culture, (2) subcutaneous inoculation with a small dose of F. necrophorum mixed with a large but relatively harmless dose of Staphylococcus aureus, and (3) intravenous inoculation with a large dose of a pure culture. Fourteen strains, all of animal origin, showed the characteristic behaviour of biotype A. Twenty-eight strains, 10 of animal origin and 18 from man, were classified as biotype B. The remaining four strains, all from man, produced a distinct type of infection in mice; these strains were referred to as 'A2433-like' because of their resemblance to a strain described in an earlier study. It would appear that biotype A strains, responsible for classical necrobacillosis in animals, do not infect man; that biotype B strains occur in both man and animals; and that 'A2433-like' strains are probably confined to man.

The effects of lesions of the habenula nucleus on lever press behaviour during a tandem operant schedule with contrasting response requirements.

The effect of bilateral lesions of the habenula nuclei in male Lister hooded rats was assessed in performance of a well learned complex tandem operant reinforcement schedule. The schedule requirement involved two successive and contrasting components in which 15 operant lever press responses followed by inhibition of the same response for a period of 15 s provided liquid-food reinforcement. Initially little disruption of performance was seen when each component of the schedule was differentially signalled with an external cue. However, relative to controls, lesioned animals showed an increasing disruption of performance when such cues were omitted. The deficit in performance of lesioned animals was not a simple failure to inhibit responding that could be predicted from an altered input from septal areas. It is suggested that these behavioural data are consistent with the anatomical evidence for the habenula as a functional relay for the integration of information from limbic structures and the striatum and that lesions of the habenula affect the ability of animals to maintain effective response strategies, particularly when these are under intrinsic control.

Double-blind comparison of two similar lotion formulations, one without and the other with hydrocortisone acetate ('Actinac') in the treatment of acne vulgaris.

A double-blind, randomized trial was carried out in 44 patients with acne vulgaris to assess the effectiveness of two similar topical combination preparations, one containing hydrocortisone acetate ('Actinac') and the other without the steroid, when applied in lotion form. Patients used one or other of the two formulations twice daily for the first 4 days and then at night only for the remainder of the 3-month study period. The results showed that both treatments were effective but the full formulation-treated group showed a better response at the end of the first month's treatment in terms of percentage reduction in lesion count score, although this did not reach statistical significance. After 3 months, the average lesion count scores dropped from 82 to 11 in the full formulation and from 81 to 8 in the formulation minus hydrocortisone group.

Treatment of acne vulgaris comparing two similar lotion formulations, one with ('Actinac') and one without chloramphenicol.

A double-blind, randomized study was carried out in 37 patients with acne vulgaris to compare the efficacy of two similar lotion formulations, one with ('Actinac') and the other without chloramphenicol (4%). Patients used one or other of the two formulations twice daily for the first 4 days and then at night only for the remainder of the 3-month trial period. At the end of the first month's treatment, the group treated with the full formulation showed a statistically significant greater reduction in lesion count score than in the group receiving the formulation without chloramphenicol. Both treatments produced statistically significant reductions in lesion counts at all monthly follow-up visits. After 3-months' treatment, the mean lesion count score was reduced from 28.8 to 9.3 in the full formulation-treated group and from 39.5 to 14.3 in the formulation minus chloramphenicol group, but this difference did not reach statistical significance.