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Biomedical subjects

J D Macfarlane

Publications and source records attributed to J D Macfarlane.

At least 19 recordsLinked to original sources
PubMed1998

Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.

Adult↗
PubMed1995

Spinal cord compression in renal osteodystrophy.

A patient undergoing regular haemodialysis for chronic renal insufficiency developed neck pain followed by progressive spinal cord compression due to subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led to an almost complete recovery. A review of all the histological specimens suggested that hyperparathyroidism and not amyloidosis caused the vertebral destruction.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed1995

Idiopathic haemochromatosis: magnetic resonance signal intensity ratios permit non-invasive diagnosis of low levels of iron overload.

OBJECTIVE: The detection of low levels of iron overload by magnetic resonance imaging. METHODS: Eight consecutive patients suspected of having idiopathic haemochromatosis. Comparison of signal intensity ratios and absolute iron content of liver. RESULTS: There was a good correlation between the signal intensity ratios and iron content in the range 2-30 micrograms Fe/mg dry weight. CONCLUSIONS: The ability of a non-invasive technique to detect low levels of iron overload could be useful in the assessment of therapy and in the screening of relatives of probands with idiopathic haemochromatosis.

Adult↗
PubMed1994

Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis.

Tumour necrosis factor alpha (TNF alpha) is a critical inflammatory mediator in rheumatoid arthritis, and may therefore be a useful target for specific immunotherapy. In support of this hypothesis, we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNF alpha (cA2). We now report the results of a four-centre, randomised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis. The primary endpoint of the study was the achievement at week 4 of a Paulus 20% response, an amalgam of six clinical, observational, and laboratory variables. Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time, compared with 11 of 25 patients treated with low-dose cA2 (p = 0.0083) and 19 of 24 patients treated with high-dose cA2 (p < 0.0001). Over half of the high-dose cA2 patients responded by the more stringent 50% Paulus criteria at this time (p = 0.0005). The magnitude of these responses was impressive, with maximum mean improvements in individual disease-activity assessments, such as tender or swollen-joint counts and in serum C-reactive protein, exceeding 60% for patients on high-dose treatment. There were two severe adverse events. 1 patient on 1 mg/kg cA2 developed pneumonia ("possibly" treatment-related) and 1 on 10 mg/kg had a fracture ("probably not" treatment-related). The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis.

Adolescent↗
PubMed1994

[Osteitis in psoriasis].

A 56-year-old man was diagnosed with psoriasis, after a year with pain over the manubrium sterni, a stiff neck and shoulders and an increased erythrocyte sedimentation rate. Imaging studies revealed widening and sclerosis of the manubrium sterni, ossification of the insertions of the first ribs and involvement of the sternoclavicular joints. Histological examination of the sternum showed signs of a chronic inflammatory process. Improvement of the skin lesions was accompanied by a reduction of the pain. Psoriasis may be complicated by osteitis/hyperostosis, which may precede the skin lesions. An effective therapy is lacking, although analgetics and antiphlogistics are often useful.

Arthritis, Psoriatic↗
PubMed1994

Gastric outlet obstruction as a presenting manifestation of systemic lupus erythematosus.

A patient with nausea and vomiting who subsequently proved to have systemic lupus erythematosus is described. Although gastrointestinal involvement is common in systemic lupus erythematosus it is rare as an initial manifestation. Gastric outlet obstruction was shown on the air contrast examination while the mucosa at endoscopy was normal. The gastric symptoms regressed after treatment with high dose corticosteroids and a repeat air contrast examination of the stomach was normal. This stricturing process may have been caused by a local peritonitis.

Adult↗
PubMed1992

Phenotypically dissimilar hypophosphatasia in two sibships.

Autosomal dominant and autosomal recessive forms of hypophosphatasia have been reported; generally the clinical picture runs true to form in families. In each of 2 kindreds, 2 sibs were clinically affected by hypophosphatasia to a markedly different extent. One set of sibs showed the lethal (perinatal) and infantile forms. The other showed the dental and adult forms. In both families there was consanguinity, albeit distant, and clinical expression in sibs supporting autosomal recessive inheritance.

Adult↗
PubMed1992

Inclusion body myositis: its relative frequency in elderly people.

Inclusion body myositis (IBM) is a distinct, steroid resistant, form of inflammatory myopathy. Its recognition is the more important because of the preponderant occurrence in the elderly, in whom steroid treatment is hazardous. Since the relative frequency of IBM among inflammatory myopathies in the elderly is undetermined, we retrospectively studied its frequency among all our patients over 50 years, diagnosed between 1980 and 1991 with inflammatory myopathy. Nine of 15 patients with inflammatory myopathy appeared to suffer from IBM. In a further 2 patients this diagnosis was strongly suspected. We conclude that IBM is the most frequent inflammatory myopathy in the elderly. This observation warrants restraint with steroids in the management of inflammatory myopathy in the elderly.

Aged↗
PubMed1992

Clinical significance of a low serum alkaline phosphatase.

The reasons for a low serum alkaline phosphatase activity were reviewed in a 1-yr retrospective study of all the results emanating from a central, university hospital laboratory. Apart from occasional errors, hypophosphatasaemia was encountered in neonates undergoing exchange transfusions with plasma, in patients (particularly children) receiving chemotherapy and during cardio-pulmonary bypass. Low activity values were recorded in several individuals in the absence of any obvious cause. This would suggest that the definition of the lower limit of the reference range for alkaline phosphatase is arbitrary, thus limiting the use of low serum activity as a marker of disease.

Adult↗
PubMed1991

Raised urinary excretion of inorganic pyrophosphate in asymptomatic members of a hypophosphatasia kindred.

We report the screening of an Anglo-Welsh kindred in which two children were affected by different clinical forms of hypophosphatasia. Among the clinically normal adult members of the kindred, a raised urinary concentration of pyrophosphate was the commonest biochemical abnormality. The concentration of phosphate in serum was elevated in only one adult member of the kindred, the mother of the propositus. Consanguinity in this kindred suggests probable recessive inheritance, and the obligate heterozygotes each exhibited a low serum AP activity plus one other biochemical abnormality indicative of a carrier state.

Adult↗
PubMed1991

Serum osteocalcin levels before and after 1,25 dihydroxy-vitamin D stimulation in a family with hypophosphatasia.

Because defective bone mineralization occurs in hypophosphatasia (HP) and the source of bone alkaline phosphatase is the osteoblast, we investigated another marker of osteoblast activity, namely the production of osteocalcin in an HP family and controls. The mean basal osteocalcin levels in the two affected young adults and their parents (the apparent heterozygotes) were 3.4 ng/ml (range 2.5-4.6) and were not different from the levels in age- and sex-matched controls (3.6 ng/ml; range 2.5-4.6). Furthermore, the ratio of carboxylated to total osteocalcin was normal. The rise in osteocalcin after 1,25-dihydroxycholecalciferol stimulation (2 micrograms daily for one week) was slightly greater in the controls than in the HP family. These results support the concept that there is no global defect in osteoblast function in this family with HP.

Adult↗
PubMed1991

Serum-sickness-like illness as a complication after streptokinase therapy for acute myocardial infarction.

We report a case of serum-sickness-like illness in a 47-year-old patient who received early high-dose intravenous and intracoronary streptokinase following acute myocardial infarction. The picture comprised severe arthralgias, fever, an urticarial rash and marked elevation of circulating immune complexes. This case represents a rare complication of streptokinase therapy.

Antigen-Antibody Complex↗