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Biomedical subjects

A H Mackenzie

Publications and source records attributed to A H Mackenzie.

At least 19 recordsLinked to original sources
PubMed1991

Folate supplementation in methotrexate-treated rheumatoid arthritis patients.

Two hundred rheumatoid arthritis (RA) patients taking low dose methotrexate (MTX) were evaluated for adverse effects. During a mean follow up of 41.5 months, the mean cell volume (MCV) was elevated at some time during the course of treatment in 42 patients. The MCV was normal in the remaining 158 patients. One hundred ninety-eight patients were treated simultaneously with oral folic acid. With the exception of heartburn, which was seen more often in the high MCV group, there was no difference in the frequency of adverse effects attributable to MTX between groups. Severity of side effects and the frequency of MTX dose reduction and MTX discontinuation due to toxicity were also similar between groups. This analysis suggests that elevation of MCV in RA patients treated simultaneously with MTX and folate does not predict MTX toxicity. The authors also discuss the mechanism of action of MTX with regard to folate metabolism.

Arthritis, Rheumatoid↗
PubMed1988

Differential diagnosis of rheumatoid arthritis.

The differential diagnosis of subacute or chronic polyarthritic diseases, including rheumatoid arthritis, is based on recognizing a pattern of changes, with special emphasis placed on certain key features that possess higher specificity. The clinical history is by far the most important diagnostic tool and involves clear assessment of the distribution of joint involvement, whether pain is articular or extra-articular, whether a syndrome follows trauma or infection, and the duration of the process. The distribution of involved joints is a major contributor to differential diagnosis but can be misleading unless a skilled physical examination confirms objective synovitis. If present, nodules, which represent localization of the disease process, also offer a powerful tool in differential diagnosis. Rheumatoid nodules occur in about 20 percent of patients with well-developed rheumatoid arthritis. The effects of inflammation may be clinically detectable, but laboratory tests--e.g., the erythrocyte sedimentation rate and quantitative C-reactive protein--provide the most reliable evidence of inflammation. Synovial fluid analysis may reveal inflammatory changes and other abnormalities permitting diagnosis. Rheumatoid factor is present in about 80 percent of patients with rheumatoid arthritis but is not specific for this diagnosis.

Arthritis, Rheumatoid↗
PubMed1983

Antimalarial drugs for rheumatoid arthritis.

Chloroquine and hydroxychloroquine effectively suppress rheumatoid arthritis with a superior benefit to risk ratio. Controlled studies demonstrate moderate efficacy in about 70 percent of patients. High-grade suppression is seen in 15 percent and partial suppression in 55 percent. The dropout rate for poor efficacy is 30 percent and for side effects 3 to 7 percent. Most studies show antimalarials to be almost equivalent to chrysotherapy in potency. Antimalarials are indicated for active rheumatoid arthritis not optimally controlled with nonsteroidal anti-inflammatory drugs and for all cases of progressive disease. Therapy is continued indefinitely. Safe use of these drugs depends on daily dosage. With the single exception of late stage retinopathy, other adverse effects are fully reversible. Strict adherence to three tested safety rules virtually eliminates retinopathy and prevents loss of vision: (1) limit the daily dosage: chloroquine 3.5 to 4.0 mg/kg per day or hydroxychloroquine 6.0 to 6.5 mg/kg per day based on lean body weight; (2) subject the patient to an annual ocular examination to age 65, twice annually thereafter; (3) adjust treatment for pharmacokinetic variables. The lower risk and nearly comparable efficacy make antimalarials first choice among remittive drugs.

Amodiaquine↗
PubMed1983

Pharmacologic actions of 4-aminoquinoline compounds.

The pharmacokinetics, physiologic effects, and the metabolization of chloroquine and hydroxychloroquine are all similar. Their concentrations in plasma and tissue are directly related to daily dosing. The highest concentrations are found in melanin-containing tissues, particularly the choroid and ciliary body of the eye. The pharmacologic effects of 4-aminoquinoline compounds are reviewed in detail. It is likely that the rheumatologic effectiveness of these agents is primarily related to lysosomal actions. The drug-induced lysosomal abnormalities include diminished vesicle fusion, diminished exocytosis, and reversible "lysosomal storage disease." It is likely that the retinal toxicity of these drugs is one manifestation of the altered lysosomal physiology involving the retinal pigmented epithelium. Tissue of retinal pigmented epithelium is similar to that of the bone-marrow-derived macrophage. Depression of extra-oculogram is an early sign of excessive dosage and can be used to measure potential toxicity during therapy with 4-aminoquinolines. Dosages ranging from 3.5 to 4.0 mg/kg per day for chloroquine and 6.0 to 6.5 mg/kg per day for hydroxychloroquine are clinically safe.

Aminoquinolines↗
PubMed1983

Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials.

No eye disease was detected in over 900 rheumatoid arthritis patients treated with less than 4.0 mg/kg per day of chloroquine or less than 6.5 mg/kg per day of hydroxychloroquine for a mean of about seven years. I therefore consider these dosage rates safe, since they are below the threshold of retinal toxicity. This is based on more than 6,000 patient-years of drug exposure. That dosage threshold for retinopathy appears to be 5.1 mg/kg per day for chloroquine and 7.8 mg/kg per day for hydroxychloroquine according to my studies with these compounds. The daily dosage rate, rather than total drug accumulation, seems to determine the development of eye disease. To prevent overdosage, dosing should be calculated not on the actual weight of the patient but on ideal (lean) body weight. Furthermore, the patient's renal and liver function should also be taken into account to avoid overdosage. Since exposure to light amplifies the risk of retinopathy in patients treated with antimalarials, dark sunglasses are recommended for patients spending much time in sunlight.

Arthritis, Rheumatoid↗
PubMed1979

Secondary hypertriglyceridemia and hyperlipoproteinemia in patients with primary asymptomatic gout.

We carefully selected 30 men with primary gout, rendered asymptomatic by therapy, to examine the frequency and type of hyperlipidemia and hyperlipoproteinemia, with the objective of determining whether serum uric acid, alcohol intake, liver function, kidney function, and (or) drugs were participating in the secondary lipid disorder. Sixty-one age- and sex-matched men were used as controls. About 73% of the gout patients had hypertriglyceridemia, 1.6-fold the frequency found in the control group. Types IV and IIb lipoprotein electrophoretic patterns were most prevalent in the gout group. Neither alcohol intake nor hyperuricemia, per se, seems to be the cause of the lipid and lipoprotein disorder and cannot be related to liver or kidney dysfunctions. Obesity was the major underlying factor associated with the lipidemia. The study suggests that diet and, possibly, defective clearance of triglycerides may be etiologic factors associated with the abnormal serum triacylglycerol (triglyceride) and lipoprotein concentrations in these individuals.

Blood Chemical Analysis↗