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Background: When quinacrine is injected interstitially, an intense migration of leukocytes and accumulation of various lymphokines is obtained locally, and the reaction is followed by cicatricial fibrosis. This property has been used in humans to induce tubal fibrosis in women and pleurodesis in patients with pleural effusion., Methods: In a controlled study, a single dose of 150 mg of quinacrine was injected interstitially into a C6 glioma implanted in the subcutaneous tissue of Wistar rats. Changes in size, histologic variations, and microscopic characteristics of leukocyte subpopulations infiltrating the tumor were studied by immunohistochemistry. Tumor necrosis factor and interleukin-1 beta were measured at different times in tumor homogenates., Results: The day after the injection of quinacrine, infiltration of leukocytes and macrophages was observed, accompanied by an accumulation of proinflammatory endogenous cytokines. Tumoral necrosis soon ensued; complete tumor disappearance was obtained in 72% of the animals. Cicatrization proceeded without injury of perilesional structures. In all controls injected with the vehicle, a large tumor developed (P <.0001)., Conclusions: Quinacrine, when administered interstitially in a single dose, elicits an intense local recruitment and proliferation of activated immune cells that, at the dose used in this study, induces tissue necrosis within a radius of 1 cm around the site of quinacrine injection, leaving the surrounding tissue unharmed.

It has been suggested that activation of tissue phospholipases may contribute to the development of ischemic cell injury. In the present study we sought to assess whether administration of the phospholipase inhibitor quinacrine would reduce the extent of myocardial necrosis after coronary artery occlusion. In open-chest, anesthetized dogs the left anterior descending coronary artery was ligated, and technetium-99-labeled albumin microspheres were injected into the left atrium to measure the area at risk. The animals were then randomly divided into a control group (n = 8) and a group receiving quinacrine (5 mg/kg intravenous bolus followed by a 40 micrograms/kg/min infusion for 6 hours; n = 9). The animals were killed 6 hours after occlusion, and the infarcted area was delineated by triphenyltetrazolium chloride staining. The extent of the risk region was similar in the two groups (32.3 +/- 2.1% of the left ventricle in control dogs and 34.2 +/- 3.4% in quinacrine-treated dogs). Infarct size was 86.4 +/- 8.8% of the risk region in control animals, whereas in treated dogs it averaged 62.3 +/- 6.4% of the risk region (p = 0.05). No differences were found in heart rate, arterial pressure, and rate-pressure product between the two groups. Thus administration of the phospholipase inhibitor quinacrine reduced the extent of myocardial necrosis in a model of fixed coronary artery occlusion. Preservation of membrane phospholipids, reduced formation of lipoxygenase metabolites, or both may mediate this phenomenon.

Antimalarial drugs were shown to be useful agents in the treatment of discoid and systemic lupus erythematosus in 1951. However, by 1966, fear of retinal toxicity and the availability of alternative therapies had led to limited use of antimalarials. Continued experience with these alternative therapies has made their intrinsic, sometimes devastating toxicities more evident and has contributed to the renewed interest in antimalarial agents evident in the number of comprehensive reviews appearing recently in the dermatology literature. Many of these reviews, while generally excellent, have propagated some apparent misconceptions by disregarding or de-emphasizing data suggesting that irreversible retinal toxicity due to antimalarials can be easily avoided by judicious daily dosage and regular ophthalmologic follow-up. This article will discuss the historical basis of these misconceptions and the subsequent studies which suggest that antimalarial retinal toxicity can be avoided without sacrificing the therapeutic efficacy of these agents.

We reviewed our experience over the past 12 years to determine the best method of management, to determine the morbidity and the physiologic outcome of medical vs surgical treatment of pneumothorax complicating CF, and to assess the influence of age, sex, and Shwachman scores on survival. Sixty-five patients, ages ranging from 5 to 32 years (mean 18 years). Shwachman scores ranging from 25 to 87 (mean 57), and a male-female ratio of 1:1, experienced 170 pneumothoraces, 93 first episodes, and 77 recurrences, requiring 211 trials of management. All methods of management except needle aspiration resulted in a fair rate of resolution (70 to 100%), but recurrence rates were high for observation (60%), needle aspiration (79%), trocar thoracotomy (63%), tetracycline sclerosis (86%), and silver nitrate sclerosis (43%). The recurrence rates were 12.5% for quinacrine sclerosis and 0% for parietal pleurectomy. Quinacrine sclerosis and parietal pleurectomy were the most effective methods of management. There was no significant difference in pulmonary function before pneumothorax and after pleural sclerosis or parietal pleurectomy. Age, sex, and severity of pulmonary disease were all independent variables influencing prognosis. Severity of disease, rather than the occurrence of a pneumothorax, appears to be the major cause of death. We recommend that quinacrine sclerosis should be considered for management of the first pneumothorax, and parietal pleurectomy if it fails.

To investigate drug sensitivities of human Giardia isolates, we developed a reproducible in vitro 3H-thymidine uptake assay to compare drug potencies. Among 13 Giardia intestinalis stocks obtained from the culture of trophozoites isolated from duodenal juice, considerable variation in susceptibility to a range of currently used drugs was found. The population doubling time of these stocks also varied widely. Clinical features in patients ranged in severity from mild chronic diarrhea to a celiac-like syndrome, with a similar variation in the degree of histologic change in the mucosa. Brush-border enzyme activities were universally reduced in children younger than 5 years of age. The two isolates with the highest ID50 values for furazolidone in vitro were from patients who had persistent symptoms after treatment with this drug; these patients subsequently responded to treatment with a nitroimidazole with greater in vitro potency. These studies suggest that biologic variants of G. intestinalis exist in humans and may in part account for the variable clinical manifestations and for some treatment failures.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.