Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis.

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0-32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0-9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.

Morphological changes in the small intestinal smooth muscle layers of horses suffering from small intestinal strangulation. Is there a basis for predisposition for reduced contractility?

REASONS FOR PERFORMING STUDY: Intestinal strangulation often leads to enterectomy after which ileus can develop. This has prompted research to look into possible pathophysiological processes triggering equine ileus. However, morphological changes of the small intestinal smooth muscle in relation to equine colic have not yet been studied. OBJECTIVES: The presence of some smooth muscle proteins was morphologically assessed and quantified in control and colic horses. In addition, the up- or down-regulation of heat shock proteins (HSP20 and HSP27) influencing the contractility of smooth muscles was studied. METHODS: Cranial resection margins of 18 strangulated small intestinal samples were collected. Small intestinal control samples were collected from 11 horses subjected to euthanasia for other than gastrointestinal-related reasons. Formaldehyde-fixed tissue was paraffin-embedded and processed for conventional staining and immunohistochemistry. Snap-frozen full-thickness biopsies were collected for western blot analyses. RESULTS: Evaluating the muscle layer microscopically, colic samples showed significantly more signs of degradation than controls (P = 0.026) of which vacuolar degeneration was most prominent (P = 0.009). In colic samples, myosin protein levels were decreased (P = 0.022) whereas desmin (P = 0.049) and HSP20 protein levels (P = 0.005) were elevated. CONCLUSIONS: In colic samples, microscopic lesions at the level of the muscle layer indicate a stress response. In addition, modified amounts of structural proteins such as myosin and desmin together with increased HSP20 levels could perhaps provide a basis for explaining the malfunctioning of the intestinal muscle layer. POTENTIAL RELEVANCE: Post operative ileus, following small intestinal strangulation and resection, could be related in part to a dysfunctional muscle layer. In addition to microscopic signs of degeneration, myosin and HSP20 were affected. Pharmacological interventions might alter HSP20 expressions and thus serve a protective effect.

The use of slaughterhouse-obtained small intestinal tissue as control material in histological studies should be applied with prudence.

This study aimed to evaluate the reliability of slaughterhouse-obtained small intestinal tissue as control material in equine colic research where molecular stress responses in small intestinal tissue are investigated. For this purpose, small intestinal samples from colic horses were collected during surgery or immediately after euthanasia at the oral border of strangulation resection sites and routinely processed for histopathology (i.c. rinsed with 4°C Krebs' solution, fixated overnight with 4% neutral buffered formaldehyde (FH) at room temperature). Control samples consisted of pieces of mid-jejunum, collected at the slaughterhouse and routinely processed for histopathology under 4 different conditions. The 4 conditions differed with regard to incubation and fixation temperature and whether or not oxygenated Krebs' solution was used. Histological scoring revealed that slaughterhouse samples had a higher mean lesion score (P<0.001) than colic samples. In addition, more slaughterhouse samples had a higher mean inflammation score than colic samples (P=0.001). The inflammatory cells in the small intestine consisted mostly of eosinophils and as such were very suggestive for parasitic infestation. Hypoxia-inducible factor-1α (HIF1α) nuclear immunoreactivity was more pronounced in slaughterhouse tissue, probably as a result of the delay between slaughter and sampling (P=0.034). The histopathological score (P=0.291), the inflammation score (P=0.248) and the HIF1α nuclear immunoreactivity (P=0.538) did not differ between the different collection protocols. It is concluded that slaughterhouse-obtained small intestinal tissue shows distinct alterations and that its use as control tissue when evaluating molecular stress responses should be applied with prudence.

Morphological data indicate a stress response at the oral border of strangulated small intestine in horses.

Strangulation colic often leads to surgery. We aimed to document the molecular response in the non-resected intestine in these horses using quantitative Western blot analysis, and immunohistochemistry. The expression of hypoxia-inducible factor 1-alpha (HIF1α) was investigated together with two molecular pathways initiated after protein destruction: proteasome degradation via ubiquitin chain formation and protein restoration via molecular chaperones such as inducible heat shock protein 70 (HSP70). In addition, the expression of c-fos and c-jun could indicate an early proinflammatory response. Ubiquitin, HSP70, c-jun and c-fos protein levels did not differ between the control and colic samples nor were they related to the clinical outcome in case of strangulation colic. However, the immunohistochemical distribution of several of these proteins (ubiquitin, HSP70 and c-jun) differed significantly between colic and control samples. The elevated presence of ubiquitin in the enterocytes' nucleus, of HSP70 in the smooth muscle cells' nucleus and of c-jun in enteric neurons suggest protective and degenerative pathways are activated in the apparently healthy non-resected tissue in case of strangulation obstruction, perhaps providing a molecular and morphological basis for the development of complications like post-operative ileus.

Factors influencing adherence to medications in a group of patients with systemic lupus erythematosus in Jamaica.

The objective of this study was to examine the factors influencing adherence to medications in a group of patients with systemic lupus erythematosus (SLE) in Jamaica. A qualitative study was designed using a screening questionnaire and semi-structured interviews. The study was conducted in the rheumatology clinic at the University Hospital of the West Indies, Kingston, Jamaica. 75 patients with SLE including 20 interviewees, who had SLE for at least 1 year participated in the study. The main outcome measures were: (i) level of self-reported adherence in a sample of the clinic attendees and (ii) interviewees explanations of the reasons for taking or not taking drugs as prescribed by their physician. 56% of the 75 study participants reported taking their medications more than 85% of the time. High cost and poor availability of medications were the main reasons for poor adherence, but some patients chose not to take their medications because of side effects, perceived mild severity of their disease and/or a preference to take drugs only when symptomatic. Patients used herbal medicines to counteract side effects of Western medicines, to 'purge the blood' and to manage lupus symptoms when they had no medications. Religious beliefs were used as a coping strategy. Traditional use of herbal medicines is common particularly in patients from rural Jamaica, and may explain the observed use of herbal medicines in those who have emigrated to developed countries. Socio-economic constraints and poor drug availability are particularly important influences on poor adherence in Jamaican patients with SLE. Religious beliefs and use of herbal remedies do not seem to affect adherence adversely but are used when drugs cannot be obtained.

Interstitial cells of Cajal and their role in veterinary gastrointestinal pathologies.

This study highlights the importance of interstitial cells of Cajal (ICs) in gastrointestinal disease. Human research is already considering IC pathologies but in veterinary research IC pathologies are rarely studied. Nevertheless, recent studies of ICs show a growing interest in the pathophysiology of gastrointestinal diseases and emphasize the consideration of this cell type in the pathophysiology of veterinary gastrointestinal malfunctions.

Lipid profile in eggs of Araucana hens compared with Lohmann Selected Leghorn and ISA Brown hens given diets with different fat sources.

1. In a cross-over trial, the egg cholesterol and fatty acid composition of Araucana hens was compared with those of two commercial breeds (Lohmann Selected Leghorn and ISA Brown) under two feeding regimes, either high (Hn-3) or low (Ln-3) in long-chain n-3 fatty acids. 2. The Hn-3 diet was formed by isocaloric substitution of animal fat in the control diet (Ln-3) by a dry product containing stabilised fish oil with standardised concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). 3. Both breed and diet had influences on egg composition, without interactions. 4. The Araucana breed showed lower feed intake and lower egg weights than the other two breeds. The yolk weight was similar, leading to a much higher yolk:albumen ratio in the Araucana eggs. 5. In comparison to commercial breeds, Araucanas produced eggs with higher cholesterol content per g of yolk, which was even more pronounced when expressed per g of egg, due to the high yolk content of the eggs. The cholesterol content of an egg remained unchanged by the diet, irrespective of the dietary fat source. 6. Changing to the Hn-3 diet led to greater concentrations of polyunsaturated fatty acids (PUFA) and lower concentrations of monounsaturated fatty acids (MUFA) contents in the yolk, without a change in the ratio of saturated (SFA) to unsaturated fatty acids (UFA). 7. Within the PUFA, the n-3 fatty acids increased at the expense of the n-6 fatty acids, indicating a competition between n-3 and n-6 fatty acids for incorporation in the yolk.

Osteoarticular disorders of haematological origin.

Clinical abnormalities of the musculoskeletal system may be the first manifestation of sickle haemoglobinopathies, leukaemias, lymphomas and haemophilia. In addition to this, known patients with these diseases exhibit a variety of osteoarticular features. The painful crisis is the most common manifestation of sickle cell disorders, but avascular necrosis, osteomyelitis and various forms of arthritides are also common. In haematological malignancies, bone pain and arthritis may occur at any stage of the disease. The diagnosis must be confirmed by the presence of malignant cells on histological examination of various samples. Haemarthrosis is the main symptom of haemophilia. It needs early treatment to avoid damage to the joints. The availability of new safe coagulation factors has improved the prognosis of haemophilia.

Abnormal plasma and serum viscosity in systemic lupus erythematosus (SLE): a Jamaican study.

Vascular complications occur frequently in SLE, and their development may be related to haemorheological derangements. However, the range of rheological abnormality in Jamaican SLE patients have not been studied. The present investigation was aimed at determining the changes in the three major blood proteins, namely fibrinogen, albumin and globulin, and their effect on plasma and serum viscosity in SLE patients during the course of treatment. The concentrations of fibrinogen and globulin were significantly increased (p<0.001), while albumin was decreased (p<0.05) in the SLE patients as compared with the control group. This increase in the fibrinogen and globulin contributed significantly to the rise of both serum and plasma viscosity. SLE patients with more severe disease had higher serum viscosity values, suggesting that serum viscosity values may provide an important marker for disease severity.

Antiphospholipid antibodies in homozygous sickle cell disease.

Serum samples from 108 unselected Jamaican patients with homozygous sickle cell disease and 116 control subjects with normal haemoglobin were screened for the presence of antiphospholipid antibodies. Slightly increased levels of IgG antiphospholipid antibodies were found in nine patients with sickle cell disease and in none of the control subjects. Serial control samples confirmed the increased levels of antiphospholipid antibodies. A comparison of the haematological and clinical features of patients with positive and negative antiphospholipid sickle cell disease did not highlight any differences between the groups.

Peak expiratory flow rate and the acute chest syndrome in homozygous sickle cell disease.

The peak expiratory flow rate (PEFR) was studied in 20 matched pairs of children with homozygous sickle cell disease with either no episodes or six or more episodes of acute chest syndrome. The pairs were carefully matched for height and a highly significant reduction in PEFR was observed in children with multiple episodes of acute chest syndrome. Lateral and anteroposterior chest diameters and chest circumference correlated with PEFR but did not differ between index and control cases. The most likely cause of the reduced PEFR in children with multiple episodes of acute chest syndrome is an accumulating pulmonary fibrosis that decreases lung compliance.

The haematology of homozygous sickle cell disease after the age of 40 years.

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Measurement of glomerular filtration rate in homozygous sickle cell disease: a comparison of 51Cr-EDTA clearance, creatinine clearance, serum creatinine and beta 2 microglobulin.

Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population.

Mortality of Jamaican patients with systemic lupus erythematosus.

A retrospective study of all patients with systemic lupus erythematosus (SLE) who died at the University Hospital of the West Indies over a 14-year period is presented. The major cause of death was infection followed by renal failure. Gram-negative organisms were the major microbiological agents causing infections. Side-effects of therapy were common, in particular bone marrow depression and haemorrhage related to anticoagulants. It appears that controlling severe lupus activity without increasing the risk of lifethreatening complications remains an important goal in the treatment of SLE.

Arthritis in childhood. A report on 65 consecutive cases observed at the University Hospital of the West Indies.

In a two-year period (October 1985 - September 1987), 65 children presented to the Child Health department and/or rheumatology clinic at the University Hospital with arthritis. Eighteen children (28%) had Juvenile Chronic Arthritis, ten (15%) rheumatic fever, eight (12%) systemic lupus erythematosus and thirteen (20%) had self-limiting arthritis. Systemic onset of Juvenile Chronic Arthritis occurred only in one child; nine children had polyarticular and eight pauci-articular onset of disease. The self-limiting arthritis was difficult to differentiate from Juvenile Chronic Arthritis; therefore serological testing for bacterial and viral infections should be performed before anti-rheumatic therapy is undertaken. Arthritis in childhood is not uncommon in Jamaica. However, the outcome appears to be generally favorable except in a few cases of Juvenile Chronic Arthritis.

Lack of relation between human T-lymphotropic virus type I infection and systemic lupus erythematosus in Jamaica, West Indies.

To determine whether systemic lupus erythematosus (SLE) is associated with human T-lymphotropic virus, type I (HTLV-I) infection in Jamaica, an endemic area for the virus, we studied 63 patients with SLE at the University Hospital of the West Indies in Kingston. Antibodies to HTLV-I were measured by an enzyme-linked immunosorbent assay (ELISA) technique using purified disrupted whole virus as antigen, with confirmation by p24 protein RIA or competitive binding. Four of 63 SLE patients were HTLV-I seropositive (6.3%). There was no evidence for excess HTLV-I infection in SLE patients when their age- and sex-standardized HTLV-I seroprevalence rate was compared to that of a large group of healthy food service employees. None of 13 patients with rheumatoid arthritis were seropositive for HTLV-I. We conclude that HTLV-I infection does not appear to be linked with SLE in Jamaica.

Complement and immunoglobulin levels in early childhood in homozygous sickle cell disease.

Complement levels, tests of complement function, and immunoglobulin levels were studied in 63 children with homozygous sickle cell (SS) disease and in 88 children with a normal haemoglobin (AA) genotype from birth to 2 yr of age. Levels of complement component C3 were consistently lower in SS children, the difference being highly significant (p less than 0.001) by the age of 2 yr and levels of C3d were significantly higher from the age of 6 months. These observations are compatible with increased turnover of C3 in SS disease from early in life. No consistent genotype differences were observed in the levels of C4, factor B, or functional assays. IgA levels in SS disease were significantly higher at age 2 yr but there were no consistent patterns with IgM or IgG. There was no difference in the prevalence of infections between groups with low C3 or low values of alternative pathway activity but the groups were small and only capable of detecting major differences. However, the findings cast some doubt on the role of individual complement deficiencies in the susceptibility to infection in SS children at this age.

Stilboestrol and stuttering priapism in homozygous sickle-cell disease.

A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering attacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks.

Pneumonia in young children with homozygous sickle cell disease: risk and clinical features.

The incidence and clinical features of pneumonia have been examined in children with homozygous sickle cell (SS) disease and in age/sex matched control children with a normal haemoglobin (AA) genotype followed in a cohort study of sickle cell disease from birth. Survival curve analysis indicated a similar incidence of pneumonia in the two genotypes up to the ages of 8 months after which pneumonia became significantly more prevalent in SS disease, the relative risk exceeding a factor of four by 4 years of age. Children with SS disease were also more prone to multiple episodes. Comparison of clinical features in the two genotypes yielded no difference in sex or seasonal involvement, or in the results of bacteriological and radiological investigations. Children with SS disease and pneumonia had an increased frequency and increased duration of hospital admission, and mortality was confined to this group. It is concluded that children with SS disease have an increased prevalence of single and multiple attacks of pneumonia and that these events run a more serious clinical course than in control children.