Determination of distribution of diffusing capacity in relation to blood flow in the human lung.

A method for appraising the distribution of diffusing capacity of the lungs (D(L)) in relationship to pulmonary capillary blood flow ([unk]Q(C)) in normal human subjects was derived from measurements of oxygen diffusing capacity (D(LO2)) and carbon monoxide diffusing capacity (D(LCO)) performed during breath holding. This method utilizes the fact that the observed D(LO2) is considerably reduced in value if uneven distribution of D(L) with respect to [unk]Q(C) (uneven D(L)/[unk]Q(C)) is present. In contrast, D(LCO) is barely affected by uneven D(L)/[unk]Q(C), and from its measured value one can calculate the value D(LO2) would have if no uneven D(L)/[unk]Q(C) were present (true D(LO2)). Once observed D(LO2) and true D(LO2) are known, the degree of uneven D(L)/[unk]Q(C) in the lung can be calculated. In five normal, resting, sitting subjects average values for true D(LO2) were 57 ml per (minute x mm Hg), and the directly measured D(LO2) was 33 ml per (minute x mm Hg). These values could be explained if one-half of total [unk]Q(C) were distributed to approximately 15% of total D(L). These measurements did not permit the determination of the alveolar to end capillary O(2) gradient, but calculations demonstrate that an important factor in determining its size may be the pattern of uneven D(L)/[unk]Q(C) present in the lungs. Estimations of the alveolar-end capillary O(2) gradient from measurements of D(LCO) or D(LO2) that do not take into account uneven D(L)/[unk]Q(C) may underestimate its size.

Hydroxychloroquine treatment of rheumatoid arthritis.

A variety of placebo-controlled and open studies have demonstrated the effectiveness of hydroxychloroquine in the treatment of rheumatoid arthritis. The excellent responses to recurrent treatment in a sample patient illustrate the value of hydroxychloroquine. Because low daily doses of hydroxychloroquine are associated with greater ophthalmologic safety, it would be advantageous to use the smallest effective daily dose, but there are no published controlled efficacy studies using daily doses of less than 400 mg. Hydroxychloroquine may best be employed to treat patients with new onset of disease or those in whom disease is not rapidly progressive. Great potential exists for the use of hydroxychloroquine in combination therapy, but optimal utilization of combination regimens will require performances of additional controlled studies.

Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment.

The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. Funduscopic examinations and visual field testing with a red object must be included. Although this protocol may detect abnormalities that are not drug related, no loss of vision has developed in patients so monitored.

Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study.

To determine if long-term methotrexate-induced improvement of rheumatoid arthritis is sustained after the drug is discontinued, 10 unselected patients with responses to weekly oral methotrexate given for at least 36 months (mean 40.1) were randomly assigned to receive methotrexate or identical-appearing placebo tablets for two months. After one month, all five patients receiving placebo had to have the study terminated due to a flare of their disease manifested by statistically significant deterioration in multiple clinical parameters. It is concluded that patients receiving long-term methotrexate must continue the drug to maintain clinical benefits.

Acquired immunodeficiency syndrome-associated arthritis.

A subacute, oligoarthritic syndrome developed in four patients with human immunodeficiency virus (HIV) infection. Three had true acquired immunodeficiency syndrome (AIDS) and all had lymphocyte abnormalities. The arthritis was characterized by extreme pain and disability in three patients and moderate pain in one. Knees and ankles were affected. Symptoms developed over a one- to six-week interval; response to treatment was rapid, especially to intra-articular corticosteroids. Despite the clinical severity of the arthritis, synovial fluids were non-inflammatory and biopsy specimens revealed only mild chronic synovitis. A definite etiology could not be established. None of the patients had recognized infections predisposing to reactive arthritis, and the three patients who underwent tissue typing were HLA-B27-negative. A viral infection, including HIV, is a possible cause. In distinction to these four patients, arthritides with clearly established etiologies developed during this same time period in four other HIV-infected patients.

Hydroxychloroquine. Seven-year experience.

Ninety-nine patients were treated with hydroxychloroquine sulfate for connective tissue diseases during a seven year period. All patients received the medication for at least one year and most were treated with a daily dosage of 400 mg. Four patients experienced toxic effects, but no patient sustained permanent loss of visual acuity. Toxicity did not seem to represent a cumulative dosage effect. Funduscopic and visual field examinations at six-month intervals are sufficient to detect the occasional adverse reactions and prevent serious retinal toxic effects when a maximum daily dosage of 400 mg is maintained.

Painful rheumatic syndromes associated with human immunodeficiency virus infection.

Severe pain is a prominent characteristic of many rheumatic conditions occurring in patients with human immunodeficiency virus (HIV) infection. These conditions may affect joints or soft tissues. Some painful syndromes, such as acquired immune deficiency syndrome-associated arthritis, may be unique to HIV-infected individuals, whereas others, such as Reiter's syndrome, may also occur in patients without HIV infection but appear more severe in infected patients. Joint and soft tissue pain is usually most intense in the lower extremities. The pathogenesis of the pain is not completely understood but may involve subclinical neuropathic disease.

Balancing effectiveness and toxicity of levamisole in the treatment of rheumatoid arthritis.

One hundred and forty-four courses of levamisole were given in various dosage schedules for the treatment of rheumatoid arthritis from 1976 to 1980. A placebo-controlled double-blinded study was analyzed traditionally and life table analysis used to describe events during follow-up. Lower dosage was significantly less toxic, but not significantly better than placebo. Toxicity to other slow acting anti-rheumatic drugs did not predispose to levamisole toxicity. Because effective doses are poorly tolerated, and tolerable lower doses are relatively ineffective, levamisole cannot be recommended as standard treatment of rheumatoid arthritis.

Toxicity of antimalarial drugs in rheumatoid arthritis.

Antimalarials have the lowest incidence of toxicity among the disease modifying antirheumatic drugs (DMARDs). Low daily dose and regular ophthalmologic examination has minimised potential retinopathy. Some toxicity may be related to the lysosomotropic action of antimalarials. DMARD toxicity may affect the variability in response to antirheumatic drugs.

Ophthalmologic considerations in using antimalarials in the United States.

Ophthalmologic considerations continue to be important in the use of antimalarials. In the United States, hydroxychloroquine is prescribed much more frequently than chloroquine. Despite the favorable safety record, potential retinal problems cause patients to often be afraid to take antimalarial medicine. Ophthalmologic visits are recommended every three months by the drug manufacturer, but most often are scheduled every six months by physicians. Ophthalmologic examination includes questioning about visual symptoms, visual acuity tests, careful fundoscopic evaluation and a visual field assessment. Amsler grid self evaluation is not yet wide-spread.

Ophthalmologic safety profile of antimalarial drugs.

The ophthalmologic safety of antimalarial drugs is well established, but absolute safety cannot be assured. Three types of side effects may develop. Corneal deposits and neuromuscular-associated blurred vision are always reversible and therefore benign. Visual loss has occurred in patients with retinopathy. Retinopathy may be divided into true retinopathy and premaculopathy. It is true retinopathy that may be associated with visual loss, while premaculopathy consists of subtle visual field and funduscopic abnormalities. These premaculopathic changes are generally completely reversible with drug discontinuation and have not been shown to progress. Hydroxychloroquine appears safer than chloroquine when currently accepted equivalent doses are used. Fewer than 20 patients with true retinopathy caused by hydroxychloroquine have been reported; more patients have developed true retinopathy when taking chloroquine. The safety profile is most dependent on low daily dose and regular ophthalmologic monitoring. The optimal strategy of ophthalmologic testing has not yet been determined, but visual acuity, funduscopic examination and visual field examination should be monitored. Self-administered ophthalmologic testing with Amsler grids may contribute additional safety but is not a replacement for physician testing.

Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study.

A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.

Exercise for rheumatoid arthritis.

The approach to treating rheumatoid arthritis is changing. Greater emphasis on the exercise component of physical therapy can improve patients' muscle strength, endurance, and emotional well-being, and may even result in decreased joint inflammation.

Heterogeneity of the clinical syndrome in patients with systemic lupus erythematosus and genetic deficiency of the second complement component.

Two patients with systemic lupus erythematosus associated with homozygous deficiency of the second complement component (SLE-C2D) illustrate the different clinical disease patterns found in patients with this illness. Despite the differences in extent and severity of clinical manifestations and serological findings, the renal disease was similar and kidney function was well preserved in both patients. Renal microscopic changes were focal and segmental, deposits of immuno-globulins and complement components were present by immunofluorescent staining, and dense deposits were seen by electron microscopy. Tubulo-reticular inclusion bodies were found in glomerular endothelial cells and lymphocytes of both patients, but not in the lymphocytes of a clinically healthy C2D sibling. The findings in these two patients stress the importance of careful evaluation to determine the presence of systemic disease in patients with SLE-C2D and suggest that an intact classic complement pathway is important in the development of severe lupus, nephritis, but is not needed in the pathogenesis of lupus skin lesions.

Development of giant cell (temporal) arteritis in a patient 'adequately' treated for polymyalgia rheumatica.

A 70-year-old woman presenting with typical polymyalgia rheumatica (PMR) and a normal temporal artery biopsy appeared to respond completely to low-dose prednisone therapy. A subsequent biopsy showing temporal arteritis with a normal sedimentation rate and no recurrence of myalgic symptoms emphasizes the unpredictable course of treated PMR and the need for continued clinical as well as laboratory follow-up.

Pseudogout in ochronosis. Report of a case.

Calcium pyrophosphate dihydrate crystals were identified in synovial fluid white blood cells during an episode of acute arthritis in a patient with ochronosis and chondrocalcinosis. Review of the histories and radiographs of 5 other patients with ochronosis demonstrated two additional instances of chondrocalcinosis. Both of these patients had episodes of arthritis consistent with pseudogout. This suggests that pseudogout, which has been found in increased incidence in some metabolic diseases, may also be more common in ochronosis.