heroin and Fibrosis

Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL.. Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI.. 34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation.. There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Cough; Dyspnea; Exercise Test; Fibrosis; Glucocorticoids; Heroin; Humans; Immunologic Factors; Lung; Lung Diseases, Interstitial; Narcotics; Oxygen Inhalation Therapy; Piperazines; Prednisolone; Purines; Pyridones; Quality of Life; Sildenafil Citrate; Sulfones; Thalidomide; Tubulin Modulators

Well-known complications related to drug abuse are myocardial insufficiency, myocardial infarction, endocarditis, myocarditis, aortic dissection, neurologic damages, ischemic colitis, thrombotic phenomenons, renal infarction and acute liver failure. Furthermore, microfocal fibrosis of the myocardium is found in stimulant abuse. The origin of myocardial fibrosis associated with opiate abuse (endocarditis, myocarditis, embolism) is still unclear. This question shall be investigated using immunohistochemical staining for early diagnosis of myocarditis. A quantification of myocardial interstitial leucocytic infiltrates was accomplished in 21 chronic drug abusers who died of heroin/morphine intoxication and compared to 15 normal subjects who died suddenly due to non-cardiac causes of death without intoxication (e.g. traffic accidents, head trauma). Toxicological investigations were performed and in addition, blood samples were checked to clarify the status of HIV, hepatitis A, B and C in both groups. To verify signs of inflammation, myocardial specimen from different locations were investigated with conventional histological stainings and immunohistochemical techniques for characterization and quantification of interstitial myocardial leucocytes, T-lymphocytes and macrophages. The number of cells were found up to fivefold increased in heroin addicts compared to the control group without reaching the cut-off values for immunohistochemically based diagnosis of myocarditis.

Topics: Adult; Aged; Chronic Disease; Female; Fibrosis; Forensic Toxicology; Heart; Heroin; Heroin Dependence; Humans; Immunohistochemistry; Male; Middle Aged; Myocarditis; Myocardium; Reference Values; Substance Abuse Detection; Young Adult

Young and middle-aged CBA mice were injected with "street" heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS- and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice.

Topics: Age Factors; Animals; Cells, Cultured; Concanavalin A; Fibrosis; Heroin; Lipopolysaccharides; Liver; Mice; Mice, Inbred CBA; Spleen; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Diphenhydramine (DPH)-related deaths in adults are extremely rare, and detailed autopsy studies are rarer still. Toxicologic and anatomic findings in 4 cases of suicidal DPH overdose are described and compared with findings in a database of cocaine- and heroin-related deaths. Blood DPH levels were many times higher than those considered therapeutic (5000-35,000 ng/ml versus 50-100 ng/ml). Marked pulmonary edema with visceral congestion was a constant finding. Mean lung-body weight ratios for DPH, cocaine, heroin, and trauma controls were 0.015, 0.015, 0.019, and 0.013, respectively. When normalized for body weight in this fashion, edema in DPH-related deaths was comparable to that in cocaine-related deaths. Cardiac enlargement was apparent in 3 of the 4 DPH cases, 1 with marked myocardial fibrosis. The finding of increased heart size suggests that preexisting heart disease may provide the necessary substrate for lethal cases of DPH toxicity. Pulmonary edema in these cases remains unexplained, with edema in cases of heroin-related toxicity significantly worse than that produced by cocaine or DPH (p < .0001). Because DPH and cocaine can exert similar effects on the heart, a common mechanism may produce pulmonary edema in both. A different mechanism may account for heroin-related edema.

Topics: Adolescent; Adult; Cardiomyopathy, Dilated; Cocaine; Diphenhydramine; Drug Overdose; Fatal Outcome; Female; Fibrosis; Heroin; Humans; Male; Middle Aged; Myocardium; Organ Size; Pulmonary Edema; Suicide

The hepatotoxic effect of heroin has been demonstrated in liver biopsies by morphometric analysis of four groups of patients: twenty-one drug abusers (DA) at the time of the biopsy, eighteen patients who had stopped drug consumption for at least six months (ex-DA), twelve patients with post-transfusional chronic active hepatitis (PTCAH), and eleven controls (CONTROL). Semiquantitative assessment showed the extent of sinusoidal dilatation and the inflammatory and fibrotic reaction in the terminal hepatic vein (THV). Thickening and cellularity of the venular wall and the volume density of sinusoidal lumen (Vsl) in the Zone I and III of the hepatic acinus, were also evaluated. The morphometric analysis used computerized measurements. In DA, the sinusoidal dilatation (100% of cases), the sinusoidal and THV inflammation (81% and 67.7%, respectively), localized mainly in the centrilobular zone, were more pronounced than in ex-DA, in patients with PTCAH and in CONTROL (significantly different P less than 0.0001). Conversely, the fibrotic reaction (perisinusoidal fibrosis--44.4% and perivenular fibrosis--61.1%) was more frequent in ex-DA. The THV inflammation in DA was replaced by a fibrotic matrix deposit in the THV wall (wall surface/internal surface = 2.72 +/- 0.37 in ex-DA; 1.38 +/- 0.32 in DA; 0.87 +/- 0.14 in PTCAH and 0.45 +/- 0.03 in CONTROL--significantly different P less than 0.001), associated with a perisinusoidal fibrosis, after drug withdrawal. Moreover, there was significantly decreased venular wall cellularity in ex-DA (wall surface/mesenchymal cells = 949 +/- 158 in ex-DA; 622 +/- 40 in DA; 619 +/- 61 in PTCAH; 547 +/- 23 in CONTROL--P less than 0.001). Semiquantitative and morphometric data suggest that these vascular lesions and their reversibility may be due to the direct hepatotoxic effects of heroin.

Topics: Adult; Fibrosis; Hepatic Veins; Heroin; Humans; Substance-Related Disorders; Vasculitis; Vasodilation