Pharyngoesophageal dysphagia: an under recognised, potentially fatal, but very treatable feature of systemic sclerosis.

Dysfunction of upper pharyngoesophageal region in systemic sclerosis (SSc) is infrequent, poorly recognised and poorly documented in the literature. Yet, it can have very distressing and even fatal consequences that may yet be very responsive to appropriate management. This paper documents the findings and outcome of management of a series of five patients with SSc who had pharyngoesophageal dysphagia to demonstrate the above. Following the documentation of a patient with SSc that had severe pharyngoesophageal dysphagia in 1981, this paper reports the findings in five patients with SSc presenting thereafter, having the same manifestations. Patients 1-4 who had barium swallow and fluoroscopy, demonstrated pharyngoesophageal dysfunction as basis of their symptoms. Patient 1 had fatal outcome from pulmonary haemorrhage following repeated bouts of aspiration pneumonia. Patients 2 and 3 had a long history of SSc and were on appropriate medical treatment. They developed a short history of dysphagia that resolved with additional improvements in swallowing techniques. Patient 4 had a short history of scleroderma, but severe and very distressing dysphagia that failed to respond to improved swallowing techniques alone, but responded well to the addition of medical treatment for SSc, over a 14-24 months period. Patient 5 had a short history of SSc and dysphagia that responded well to medical treatment over 6-12months. We conclude that pharyngoesophageal dysphagia in SSc, is a rare, very distressing and potentially fatal manifestation that can have a very favourable outcome with appropriate management.

Vertebral deformities and fractures are associated with MRI and pQCT measures obtained at the distal tibia and radius of postmenopausal women.

SUMMARY: We investigated the association of postmenopausal vertebral deformities and fractures with bone parameters derived from distal extremities using MRI and pQCT. Distal extremity measures showed variable degrees of association with vertebral deformities and fractures, highlighting the systemic nature of postmenopausal bone loss. INTRODUCTION: Prevalent vertebral deformities and fractures are known to predict incident further fractures. However, the association of distal extremity measures and vertebral deformities in postmenopausal women has not been fully established. METHODS: This study involved 98 postmenopausal women (age range 60-88 years, mean 70 years) with DXA BMD T-scores at either the hip or spine in the range of -1.5 to -3.5. Wedge, biconcavity, and crush deformities were computed on the basis of spine MRI. Vertebral fractures were assessed using Eastell's criterion. Distal tibia and radius stiffness was computed using MRI-based finite element analysis. BMD at the distal extremities were obtained using pQCT. RESULTS: Several distal extremity MRI and pQCT measures showed negative association with vertebral deformity on the basis of single parameter correlation (r up to 0.67) and two-parameter regression (r up to 0.76) models involving MRI stiffness and pQCT BMD. Subjects who had at least one prevalent vertebral fracture showed decreased MRI stiffness (up to 17.9 %) and pQCT density (up to 34.2 %) at the distal extremities compared to the non-fracture group. DXA lumbar spine BMD T-score was not associated with vertebral deformities. CONCLUSIONS: The association between vertebral deformities and distal extremity measures supports the notion of postmenopausal osteoporosis as a systemic phenomenon.

Micro-finite element analysis applied to high-resolution MRI reveals improved bone mechanical competence in the distal femur of female pre-professional dancers.

UNLABELLED: Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation. INTRODUCTION: The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls. METHODS: This study had institutional review board approval. We recruited nine female modern dancers (25.7±5.8 years, 1.63±0.06 m, 57.1±4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1±4.8 years, 1.6±0.04 m, 55.8±5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE=31 ms/5.1 ms, 0.234 mm×0.234 mm×1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups. RESULTS: Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p<0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p<0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p>0.07), but adjustment for cortical bone cross-sectional area did not (p<0.03). CONCLUSIONS: Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation.

Disease Activity Score 28-ESR bears a similar relationship to treatment decisions across different rheumatologists, but misclassification is too frequent to replace physician judgement.

OBJECTIVES: To determine whether physician factors are associated with disease activity status in RA, independently of 28-joint disease activity score (DAS28)-ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active disease in usual practice. METHODS: A prospective observational study of outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease was defined by an increase in therapy together with a reason of 'active disease'; very low disease activity was defined by a decrease in therapy together with a reason of 'patient well'. The independent physician effect was assessed using logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low disease activity, 37 had very low disease activity and 76 had uncertain disease activity status. There was no independent effect of physician upon active disease status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the variability in active disease status. There was a trend towards an independent effect of physician upon very low disease activity status (P = 0.06) and greater variability in the distribution of DAS28-ESR for patients in very low disease activity. DAS28-ESR thresholds showed a significant risk of misclassification for active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between groups of patients with active and non-active disease, with no evidence of additional physician-specific factors to explain disease activity status. However, DAS28-ESR is not as good for discriminating remission from non-remission status. There are appreciable probabilities of misclassification error, which make DAS28-ESR inappropriate as a sole guide for treatment decisions.

Highly stable CuO incorporated TiO(2) catalyst for photo-catalytic hydrogen production from H(2)O.

A CuO incorporated TiO(2) catalyst was found to be an active photo-catalyst for the reduction of H(2)O under sacrificial conditions. The catalytic activity originates from the photogeneration of excited electrons in the conduction bands of both TiO(2) and CuO resulting in a build-up of excess electrons in the conduction band of CuO. Consequently, the accumulation of excess electrons in CuO causes a negative shift in the Fermi level of CuO. The efficient inter-particle charge transfer leads to a higher catalytic activity and the formation of highly reduced states of TiO(2)/CuO, which are stable even under oxygen saturated condition. Negative shift in the Fermi level of CuO of the catalyst TiO(2)/CuO gains the required over-voltage necessary for efficient water reduction reaction. The function of CuO is to help the charge separation and to act as a water reduction site. The amount of CuO and crystalline structure were found to be crucial for the catalytic activity and the optimum CuO loading was ca. approximately 5-10%(w/w).

Reliable noninvasive genotyping: fantasy or reality?

Noninvasive genotyping has not gained wide application, due to the notion that it is unreliable, and also because remedial measures are time consuming and expensive. Of the wide variety of noninvasive DNA sources, dung is the most universal and most widely used in studies. We have developed collection, extraction, and amplification protocols that are inexpensive and provide a high level of success in amplifying both mitochondrial and nuclear DNA from dung. Here we demonstrate the reliability of genotyping from elephant dung using these protocols by comparing results from dung-extracted DNA to results from blood-extracted DNA. The level of error from dung extractions was only slightly higher than from blood extractions, and conducting two extractions from each sample and a single amplification from each extraction was sufficient to eliminate error. Di-, tri-, and tetranucleotide loci were equally reliable, and low DNA quantity and quality and PCR inhibitors were not a major problem in genotyping from dung. We discuss the possible causes of error in genotyping with particular reference to noninvasive samples and suggest methods of reducing such error.

Inpatient treatment of rheumatoid arthritis with synacthen depot: a double blind placebo controlled trial with 6 month followup.

OBJECTIVE: To assess the additional benefit of synacthen depot over standard inpatient care for patients hospitalized with active rheumatoid arthritis (RA). METHODS: All patients admitted to our unit with active RA without exclusion criteria were invited to participate and randomized to subcutaneous synacthen depot 0.5 mg on alternate days for 2 injections or 2 injections of saline. Patients, staff, and assessors of response were blinded to the intervention. Assessment [OMERACT set, American College of Rheumatology (ACR) global improvement, dose of intraarticular (IA) or intramuscular (IM) methylprednisolone] was performed at admission to hospital, at discharge, and at 3 and 6 months. Oral prednisone use constituted a protocol violation. RESULTS: Of 137 patients with RA admitted over the period of recruitment, 36 (26%) were enrolled; 31 completed followup. There were no between-group differences in the change from admission of any individual disease activity measure at any time point. However, using a rigorous global response measure (ACR 50%), a difference was detected in favor of synacthen depot at discharge (52.6% of the intervention group improved vs. 17.6% of controls; p = 0.029, number-needed-to-treat 2.86). Patients treated with synacthen depot showed a trend toward more IA or IM corticosteroid between discharge and 3 months (mean dose 56 vs. 31 mg; p = 0.19) and a trend toward more patients requiring a change in slow acting antirheumatic drug after discharge (4 vs. 1; p = 0.27). CONCLUSION: There is some additional benefit of synacthen depot in the hospital treatment of RA, but the effect is lost by 3 months, with a suggestion of rebound worsening in these patients. We postulate that oversuppression of corticotrophin releasing hormone by exogenous adrenocorticotrophic hormone in patients who already have a hypothalamic deficit may contribute to the rebound worsening of disease activity seen in these patients.

Bacterial infections: osteoarticular brucellosis.

Osteoarticular brucellosis has been documented extensively from the Middle East and Spain in the last 5 years, but it has only been reported infrequently from the UK and USA. Brucella melitensis from goat and sheep is the most frequently isolated organism. Peripheral articular pain, particularly of the large joints, is the commonest osteoarticular manifestation, while effusions that seldom yield organisms on culture, also occur frequently. Sacroiliitis which most frequently is unilateral, often presents acutely and dramatically with severe pain that is poorly localized to the lower back and buttock, leading to difficulty in walking and even standing. Tapping the heel and springing the sacrum is probably the best way of localizing the pain to the sacroiliac joint in this acute stage. Lack of awareness of this pattern of presentation could lead to misdiagnosis. Spondylitis is the third major manifestation of osteoarticular brucellosis. It occurs in older patients and is insidious and chronic in onset and course. The lumbar spine is most frequently involved, although cervical involvement is frequently associated with more complications, particularly compressive neurological deficits. Osteomyelitis occurs unusually. Several large series have been reported among children. In them peripheral large joint involvement in association with systemic features predominate while sacroiliitis may occur unusually. Plain X-rays often demonstrate vertebral damage, involving the upper anterior margin most frequently. CT scans define better vertebral damage that is characterized by bony sclerosis and the less frequently encountered extradural extension and para-vertebral abscess formation. Technetium bone scan is the most sensitive technique for detecting acute sacroiliitis and other sites of early osteoarticular involvement. A four-fold rise in Brucella agglutination titre is the most frequently utilized diagnostic aid. A 6 week culture in a CO2-enriched medium is recommended for growing Brucella. Tetracycline or doxycycline 200 mg per day for 6 weeks is the mainstay of most medical treatment schedules. Combination with streptomycin for 3 weeks or rifampicin for 6 weeks is recommended, to reduce significantly the failure and relapse rate. Spinal involvement is associated with an increased failure and relapse rate while they occurred least among those with no osteoarticular involvement. Surgical intervention to stabilize the spine and relieve neurological compression may become necessary. With the use of these various measures, the outlook for complete recovery is good.

Salmonella meningitis. [case report]

Salmonella infections in children occur mainly as gastroenteritis which is a self limiting disease. Typhoid is the next common form; where antiiotics are warranted. Rarely; localised infections can occur especially in the younger age groups. The patient in this case had salmonella meningitis which is a rare form of salmonella infection with a bad prognosis

Myasthenia gravis in a child. [case report]

A ten year old girl presented with a three month history of diminished vision and tiredness towards the end of the day. There were no other complaints. On examination; the patient had ptosis of the left eye which improved after a period of sleep. She was also myopic. Clinical examination was otherwise normal. There were no evidence of weakness of any ather muscles. The diagnosis with the tensilon test and the sleep test had shown that the patient had a myasthenia gravis

Myiasis due to Cardylobia anthropophaga, the 'Tumbu fly' in a Sri Lankan infant.

A case of myiasis due to Cardylobia anthropophaga (Blanchard) (Diptera: Calliphoridae), the 'Tumbu fly', is reported for the first time in Sri Lanka, in a 10 month old infant. The infection was acquired in Zimbabwe. The child had appeared 'unwell' for nearly a week before the detection of the skin lesions. The main clinical features were irritability, restlessness and the appearance of three small lumps on the scalp behind the right ear. Identification of the fly larva and the management of myiasis are discussed.

Cutaneous polyarteritis nodosa and ulcerative colitis.

Vasculitis in many forms has been reported rarely in association with ulcerative colitis. We report the occurrence of necrotizing vasculitis in a 48-year-old man 19 years after the onset of ulcerative colitis and 5 years after total colectomy with rectal preservation. The disease was limited to small arteries of skin and muscle consistent with the syndrome of cutaneous polyarteritis nodosa that has been reported with regional enteritis but not previously with ulcerative colitis.

Streptococcal antibody cross-reactivity with HLA-DR4+VE B-lymphocytes. Basis of the DR4 associated genetic predisposition to rheumatic fever and rheumatic heart disease?

B-lymphocytes obtained from patients with either rheumatic fever or rheumatic heart disease and from normal subjects were reacted with serum obtained from rabbits immunized with streptococcal cell wall antigen. The presence of cytotoxicity was sought using an inverted phase microscope after differential uptake of eosin dye. The serum was found to be significantly more cytotoxic to HLA-DR4 containing cells of both patients and normals compared with DR4 negative cells (P less than 0.0001).

A genetic marker for rheumatic heart disease.

The frequency of antigen types (A, B, C, and DR) in an unselected group of 25 patients with chronic rheumatic heart disease and an unselected group of 15 patients with acute rheumatic fever was compared with that in a group of 100 healthy volunteers. All patients and controls were Arabs of Saudi origin. Only the frequency of HLA-DR4 was significantly different in the controls and the patient groups--controls 12%, chronic rheumatic heart disease 72%, acute rheumatic fever 53%, both patient groups together 65% (relative risk 13.6 with 95% confidence interval 10.5-16.7). Eighty three per cent of 12 patients with mitral stenosis and 70% of seven with aortic incompetence had HLA-DR4 antigen. In 17 non-Saudi Arab patients who had acute rheumatic fever or chronic rheumatic heart disease, the frequency of HLA-DR4 was identical (65%) to that in Saudi patients. These findings may have implications for the pathogenesis of rheumatic fever and rheumatic heart disease.

Joint mobility and mitral valve prolapse in an Arab population.

The association of joint laxity and mitral valve prolapse (MVP) has been disputed. In this study of an Arab population, the joint mobility scores of 29 subjects with MVP, 10 of whom were asymptomatic, were compared to 60 normal controls. It was found that the joint mobility score was significantly higher in both the asymptomatic and the symptomatic subjects with MVP when compared to the controls. This suggests that both mitral valve prolapse and joint laxity may be due to the same abnormality of connective tissue structure.

Brucella meningitis.

Infection with Brucella melitensis is endemic in Saudi Arabia but involvement of the central nervous system (CNS) is rare. We report on three patients with acute brucella meningitis, all of whom had a history of exposure to a possible source of infection. Diagnosis was confirmed by isolation of Brucella species from blood cultures. Examination of cerebrospinal fluid revealed lymphocytic pleocytosis with a high concentration of protein and low concentration of glucose. The patients were treated by combinations of co-trimoxazole, doxycycline or rifampicin. All responded well without recurrences. A combination of two of the three drugs was effective in treating brucellosis of the CNS when given for a period of 6-8 weeks.