Plexogenic pulmonary hypertension associated with intravenous cocaine abuse

Intravenous drug abuse related plexogenic pulmonary hypertension unassociated with recurrent thromboembolism or foreign-body granulomatous disease of the lung has not been previously reported. Herein, we describe the occurrence of fatal plexogenic pulmonary hypertension in a 33-year-old Hispanic woman who had a history of chronic intravenous drug abuse. In the absence of other known causes, cocaine-induced chronic vasoconstriction was the most probable pathogenic mechanism of plexogenic pulmonary hypertension in this patient.     

肺灌注与通气显像诊断静注毒品者急性肺栓塞

为探讨肺灌注/通气显像对静脉注射毒品者肺栓塞的早期诊断,9例患败血症心内膜炎,急性脑梗塞患者用核素肺灌注、肺通显像进行观察,并与X线胸片、超声心动图结果进行对照,结果显示9例患者中,8例肺灌注呈双肺多节段稀蔬缺损,与通气显像不匹配,与通气显像不匹配,核医学诊断为急性肺栓塞1例溶栓治疗入病人肺灌注显像明显改善,与临床症状一致,从而证实灌注与肺通气显像联合运用对此类病人急性肺栓塞的早期诊断极有价值,并可做为溶栓治疗疗疗效的观察指标 另外也提示临床医师对静脉注射品者肺栓塞应有足够警惕.     

Nephrotic syndrome and pulmonary hypertension as complications of intravenous drug abuse

This case report discusses a patient with nephrotic syndrome, pulmonary hypertension, and repeated episodes of infections. He had a history of intravenous drug abuse. Kidney biopsy revealed the rare finding of numerous foam cells, mainly in glomeruli. The solvent used for the drugs is thought to be responsible for the foam cells. In line with previous reports, we suspect that the pulmonary hypertension is consistent with foam cells in pulmonary capillaries or fat embolism syndrome due to the intravenous administered drugs. Our case demonstrates that the use of intravenous drugs can lead to widely varying symptoms. Globally, the prevalence of substance abuse is increasing. Knowledge about their damaging effects is crucial in both clinical practice and anatomic pathology.     

The pulmonary vascular lesions of intravenous drug abuse

We examined microscopic sections of lungs from 70 autopsies on persons who abused drugs by intravenous injection in order to evaluate systematically the spectrum of pulmonary vascular lesions resulting from this practice. Angiothrombosis, the most frequent pulmonary vascular lesion, occurred in 13 instances. Morphologic subgroups of this category include weblike and eccentric intimai fibrous lesions, “plexiform-like” lesions, and aneurysmally dilated, tortuous small vessels. Thrombotic changes typically are induced by intravenous injections of solutions derived from tablets or capsules that ethically are intended for oral consumption, because oral pharmaceutical preparations usually contain insoluble microcry-stals such as talc, starch, or cellulose. Ordinary illicit heroin does not contain enough insoluble crystalline debris to induce extensive pulmonary angiothrombosis.We found only two specimens with vascular changes indicative of nonthrombotic pulmonary hypertension; one of these persons had concomitant cirrhosis of the liver, and the other had aortic and mitral valvular bacterial endocarditis. Morphometric studies of the muscular arteries in all other lung samples containing scant embolic foreign material did not show a significant difference between drug abusers and normal control subjects, a finding that fails to support the hypothesis that vasoconstriction or other nonthrombotic reactions to intravenous drug abuse cause pulmonary hypertension and cor pulmonale.     

Pulmonary veno-occlusive disease in a patient with HIV infection. A case report with autopsy findings

We relate the autopsy findings of a case of pulmonary veno-occlusive disease which occurred in an HIV-infected intravenous drug abuser. This exceedingly rare disease, of unknown cause, is responsible for 10% of primary pulmonary hypertension. Histologically, the disease is characterized by a fibrous intimal thickening of small and medium sized pulmonary veins associated with congestive and dilated capillary network and alveolar haemorrhage. The occurrence of primary pulmonary hypertension in HIV positive patients is 25 times more frequent than in the general population. This is the third reported case of pulmonary veno-occlusive disease occurring in a HIV positive patient. It suggests the role of HIV in the pathogenesis of these vascular lesions.     

Anaphylactic reaction to intravenous diclofenac

Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used as an opioid sparing agent for postoperative analgesia. Anaphylaxis due to intravenous diclofenac sodium is very rare. We report a case of anaphylactic reaction to IV diclofenac sodium, occurring postoperatively in a 25-year-old primigravida, the clinical features of which mimicked pulmonary embolism. The rarity, clinical importance and the diagnostic dilemma associated prompted us to report this case.     

The effect of isoproterenol on the development and recovery of hypoxic pulmonary hypertension. A structural and hemodynamic study.

Isoproterenol, administered intravenously during acute hypoxic exposure, is here shown to prevent about two-thirds of the rise in pulmonary artery pressure in unanesthetized male Sprague-Dawley rats with normal pulmonary vascular beds. In rats receiving continuous intravenous infusion of isoproterenol during 2 weeks' exposure to chronic hypobaric hypoxia (FiO2 0.1) the drug does not prevent either the hemodynamic or pulmonary structural changes caused by hypoxia. Similar drug administration to rats in air causes a mild increase in pulmonary artery muscularity including extension and hypertrophy of both the left and right ventricles, without changing hemodynamic findings. Isoproterenol administered during 2 weeks' recovery in air after 2 weeks' hypoxia not only prevents the usual structural recovery, but several structural features actually progress. In contrast, it does not prevent hemodynamic recovery, perhaps because the hematocrit is lower in the isoproterenol-treated rats than in rats recovering without isoproterenol. Administered in air to rats with pulmonary vascular beds remodeled by chronic hypoxia, it does not reduce pulmonary artery pressure.     

Noncardiogenic pulmonary edema induced by a molecular adsorbent recirculating system: case report

Noncardiogenic pulmonary edema is a well-recognized manifestation of acute lung injury which has been related, among others, to blood or blood-product transfusion, intravenous contrast injection, air embolism, and drug ingestion. We describe two cases of noncardiogenic pulmonary edema after use of a molecular adsorbent recirculating system, a cell-free dialysis technique. Patients in this series presented at our institution to be evaluated for liver transplantation. Subsequently, they developed an indication for the molecular adsorbent recirculating system. Two patients of 30 (6.6%) treated with the molecular adsorbent recirculating system for acute-on-chronic liver failure and intractable pruritus had normal chest X-rays before treatment and developed severe pulmonary edema, in the absence of cardiogenic causes, following use of the molecular adsorbent recirculating system. For each patient we reviewed the history of blood or blood-product transfusion, echocardiograms if available, daily chest X-rays, and when available pre- and postmolecular adsorbent recirculating systemic blood pressure, central venous pressure, pulmonary arterial pressures, cardiac output, cardiac index, systemic vascular resistance index, and arterial blood gas. Our data suggest that the molecular adsorbent recirculating system may cause noncardiogenic pulmonary edema, possibly by an immune-mediated mechanism.     

Polyelectrolyte capsules packaging BSA gels for pH-controlled drug loading and release and their antitumor activity

Polyelectrolyte multilayer capsules, promising candidates for multifunctional drug delivery systems, have recently received increased interest. However, the low encapsulation efficiency of drugs and the lack of reports about animal experiments have greatly slowed down their development for drug delivery. Here, a polyelectrolyte multilayer capsule filled with bovine serum albumin gel (BSA-gel-capsule) was constructed by a layer-by-layer assembly technique and thermally induced gelation of BSA. Owing to the charge variability of BSA with change in pH, BSA-gel-capsules not only showed a pronounced accumulation effect of drugs into capsules, but also displayed excellent pH-controlled loading and release properties. Moreover, a remarkable targeting action to the lung was discovered after intravenous injection of fluorescein isothiocyanate (FITC)-labeled BSA-gel-capsules into mice. After treatment with doxorubicin-loaded BSA-gel-capsules, effective cytotoxicity against B16-F10 cells and inhibition of the pulmonary melanoma growth were revealed. This paper introduces a new type of smart microstructure with notable pH-responsive ability. This material renders feasible the intravenous administration of polyelectrolyte microcapsules, which will be a big step towards their application as drug delivery vehicles.     

Intravenous leiomyomatosis of the uterus with multiple pulmonary metastases associated with large bullae-like cyst formation

We present a case of uterine intravenous leiomyomatosis associated with multiple pulmonary metastases with bullae-like cystic change. A 53-year-old woman who had undergone hysterectomy 5 years previously underwent an operation for multiple pulmonary nodules with bullae formation. After resection of several large bullae, a subsequent extirpation of the pulmonary nodules was performed, and a pathological examination showed multiple leiomyomatous nodules with occasional cystic change. A review of the previous slides of the uterus and immunohistochemical analysis of the proliferating ability using anti-Ki-67 and anti-proliferating cell nuclear antigen (PCNA) antibodies were performed. Proliferating cells of the uterus had very few mitotic figures for their high cellularity, and the labeling indices of Ki-67 and PCNA indicated very low levels in both uterine neoplasm and pulmonary nodules. From these findings, an intravenous leiomyomatosis associated with multiple pulmonary metastases was diagnosed.     

Intravenous zymosan-A challenge induces an alveolar inflammatory response

The purpose of this study was to evaluate the ability of intravenous zymosan-A (ZyA) challenge to induce an alveolar inflammatory response as indicated by inflammatory changes among lung lavage cells. The organ distribution of 1 mg of [⁵¹ZyA revealed that immediately following intravenous challenge of female ICR mice approximately 81 % of the total cpm injected was associated with pulmonary tissue. Approximately 15% of the injected cpm was associated with the peripheral blood, liver, andspleen. ZyA translocated from the vascular compartment into pulmonary alveoli and was detected within polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM) 18 h after intravenous challenge. PMN numbers among lung lavage cells increased beginning one day after challenge to a peak of approximately 5 × 10⁵ PMNs by day 3 after challenge. The PMN response subsided by day 5 after challenge. There was no significant increase in the numbers of AM during the first week after intravenous ZyA; however, the number of AM increased from approximately 5 × 1C5 AM on day 1 after challenge to approximately 1.1 × 106 AM by day 5 after challenge. Within 24 h of intravenous ZyA, the number of AM in S phase of the cell cycle increased from approximately 2.5 × 104 AM one day after challenge to 1.1 × 105 AM in S phase five days after challenge. The data suggest that intravenous ZyA localized within pulmonary tissue immediately following intravenous challenge and translocated into the alveolar compartment where ZyA particles were found within phagocytes. This process was accompanied by an acute PMN inflammation, an acute increase in the proliferation of mononuclear phagocytes within the alveoli, and a significant increase in AM numbers by one week after intravenous ZyA. Intravenous ZyA challenge may be used to explore acute and chronic inflammatory responses within pulmonary alveoli without the need for intratracheal challenge.     

Nocardial infection in patients infected with the human immunodeficiency virus

During the period 1981–2000, we diagnosed eight cases of HIV– Nocardia co-infection (0.38% of AIDS cases). Six were males, and the mean age was 28.6 years. The most common risk factor for HIV infection was intravenous drug abuse. Most patients were severely immunodepressed at the time of diagnosis (mean CD4⁺ count, 35 cells/µL). The clinical forms of nocardiosis seen were pulmonary infection in three, skin or soft tissue infection in three, disseminated in one, and pulmonary colonization in one. Most patients were given sulfonamides, and a clinical response was observed in six of seven treated patients. However, two patients with pulmonary disease died from progressive infection. Although its incidence is very low among AIDS patients, nocardiosis is associated with high morbidity and mortality among HIV-infected individuals.     

Current Management of Primary Pulmonary Hypertension

Primary pulmonary hypertension (PPH) is a rare disorder of the lung vasculature characterised by an increase in pulmonary artery pressure. Although the aetiology of this disease remains unknown, knowledge of the pathophysiology of the disease has advanced considerably. Diagnosis of PPH is largely by exclusion. The clinical symptoms associated with PPH are aspecific and similar to those seen in other cardiovascular and pulmonary diseases. Electrocardiography, echocardiography, pulmonary function tests, and a lung perfusion scan are necessary to exclude secondary forms of pulmonary hypertension and also help to confirm the diagnosis of PPH. A definite diagnosis of PPH is established by right-heart catheterisation which gives a precise measure of the blood pressure in the right side of the heart and the pulmonary artery, right ventricular function and cardiac output. Once a diagnosis of PPH is established, treatment involving drug therapy or surgery is commenced on the basis of the New York Heart Association functional class. Conventional treatment consists of lifetime administration of anticoagulants, oxygen, diuretics, and digoxin. Vasodilator therapy with calcium channel antagonists is indicated in patients who are ‘vasoreactive’ to acute vasodilator challenge as assessed by right-heart catheterisation. Promising results are obtained by continuous intravenous administration of epoprostenol (prostacyclin). Newer therapies for PPH include prostacyclin analogues, endothelin receptor antagonists, nitric oxide, phosphodiesterase-5 inhibitors, elastase inhibitors, and gene therapy. Surgical treatment consists of atrial septostomy, thromboendarterectomy, and lung or heart-lung transplantation.     

Eikenella corrodens endocarditis in an intravenous drug user: case report and literature review.

A rare case of Eikenella corrodens endocarditis in an intravenous drug user is reported. Repeated blood cultures from the patient established the diagnosis of this infection. However, evaluation of the cardiac function using two-dimensional echocardiography with Doppler flow demonstrated a large pedunculated tricuspid vegetation. Also evident on this study was a dilated right ventricle with diminished contractility and regurgitation. Complete sterilization of the blood was achieved after a 2-week course of intravenous penicillin and gentamicin followed by an additional 4-week course of intravenous penicillin alone. Clinicians treating suspected IV drug users should be aware of the potential pathogenicity of this rare, facultative, anaerobic gram-negative bacillus (E corrodens). A combination of intravenous penicillin and aminoglycoside should be considered as the initial treatment followed by an additional course of intravenous penicillin for such patients with valvular vegetation.     

Stimulation of pulmonary vagal C-fibres by anandamide in anaesthetized rats: role of vanilloid type 1 receptors

This study was carried out to determine the effect of intravenous injection of anandamide on pulmonary C-fibre afferents and the cardiorespiratory reflexes. In anaesthetized, spontaneously breathing rats, intravenous bolus injection of anandamide near the right atrium immediately elicited the pulmonary chemoreflex responses, characterized by apnoea, bradycardia and hypotension. After perineural treatment of both cervical vagi with capsaicin to block the conduction of C-fibres, anandamide no longer evoked these reflex responses. In open-chest, and artificially ventilated rats, anandamide injection evoked an abrupt and intense discharge in vagal pulmonary C-fibres in a dose-dependent manner. After injection of the high dose, the fibre discharge generally started within 1 s, reached a peak in ∼2 s, and returned to baseline within 7 s. The stimulation of C-fibres by anandamide was completely and reversibly blocked by pretreatment with capsazepine, a competitive antagonist of the vanilloid type 1 receptor. Anandamide (0.4 mg kg⁻¹) stimulated ∼93 % of pulmonary C-fibres that were activated by capsaicin at a much lower dose (0.6 μg kg⁻¹); the response to anandamide showed similar intensity, but had slightly longer latency and duration than that to capsaicin. In conclusion, intravenous bolus injection of anandamide evokes a consistent and distinct stimulatory effect on pulmonary C-fibre terminals, and this effect appears to be mediated through an activation of the vanilloid type 1 receptor.     

Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three subjects was confirmed by radioimmunoprecipitation assay. In the immunoblot study, only two of the three subjects were considered positive, since the serum of the third subject had antibodies to p24 only. By means of the polymerase chain reaction two participants (male intravenous drug users infected with human immunodeficiency virus; HIV) appeared to be infected with HTLV-I and one subject (a male nonintravenous drug user from Surinam) with HTLV-II. It is concluded that HTLV-I and HTLV-II circulate sporadically among drug users in Amsterdam and that risky injecting behaviour, which led to an HIV epidemic among intravenous drug users, has not led so far to an appreciable transmission of the other retroviruses among this group.     

High prevalence of occult hepatitis B virus infection in Taiwanese intravenous drug users

The epidemiology and impact of occult HBV infection in intravenous drug users remain largely unknown. The aim of the study was to investigate the prevalence of occult HBV infection among intravenous drug users in Taiwan. Molecular assays were used to determine the level of serum HBV DNA and the genotype in 304 intravenous drug users negative for both HBsAg and anti-HCV. Of 304 intravenous drug users, 125 (41.1%) were positive for serum HBV DNA. The genotype distribution of HBV was as follows: B, 55 (44%); C, 29 (23%); and mixed B and C infections, 41 (33%). The mean and median serum HBV DNA levels in 125 intravenous drug users with occult HBV infection were 4.0 +/- 0.6 and 4.0 log(10) copies/ml, respectively. The mean serum HBV DNA level in carriers with mixed genotype B and C infections was significantly higher than those infected with HBV genotype B or genotype C alone (mean, 4.2 +/- 0.6 log(10) vs. 3.9 +/- 0.5 log(10), and 3.9 +/- 0.7 log(10) copies/ml, P = 0.01 and 0.05, respectively). The amino acid sequence determination of HBV surface gene in 20 intravenous drug users with occult HBV infection selected at random showed no mutation of amino acid at codon 145. In conclusion, the prevalence of occult HBV infection and mixed HBV genotype infections are not uncommon in intravenous drug users residing in an HBV endemic areas. In addition, intravenous drug users with occult mixed genotype B and C infections have significantly higher viral loads than those with occult infection of single HBV genotype.     

Correlation of flunisolide plasma levels to eosinopenic response in humans

Plasma levels of flunisolide were measured in healthy male volunteers after the administration of single doses of the drug by the intravenous, oral, intranasal, and bronchial inhalation routes. The systemic availability of a 1-mg dose orally was only 21%. After a single dose of approximately 0.117 mg intranasally plasma levels ranged up to 1 ng/ml. When 1 mg was administered by bronchial inhalation, peak or near peak plasma levels were recorded at 2 min and remained near this level throughout the first hour before declining at a rate similar to that observed after flunisolide intravenously (plasma ). Gargling with an alcoholic mouthwash immediately after inhalation reduced plasma levels at 30 and 60 min but not earlier, suggesting rate-limiting dissolution of flunisolide in bronchial fluids or rate-limiting diffusion across the mucociliary blanket or pulmonary membrane. The systemic availabilities of the inhaled-mouthwash and inhaled-no mouthwash doses were 32% and 39%, respectively. Systemic potency of flunisolide, measured by eosinopenic response, was oral < inhaled < intravenous and correlated with the systemic availability of flunisolide after drug administration by these three routes. These pharmacokinetic properties of flunisolide are clinically advantageous in that relatively small doses are delivered topically to the target organs, i.e., the nasal mucosa and lungs, whereas a large portion of the dose is swallowed and subsequently extensively metabolized to relatively inactive metabolites.     

Infective Endocarditis due to Fusobacterium nucleatum in an Intravenous Drug Abuser

 Infective endocarditis due to anaerobic non-spore-forming gram-negative bacilli in intravenous drug abusers is exceedingly rare, with only two cases being previously reported in the literature. A case of endocarditis due to Fusobacterium nucleatum in an intravenous drug abuser is reported, accompanied by a review of the literature.     

Human immunodeficiency virus infection in a Dublin general practice.

A group general practice in Dublin's inner city has had extensive experience of intravenous drug users since the late 1970s. Since 1985 a total of 54 human immunodeficiency virus (HIV) seropositive patients have attended the practice, of whom 48 are intravenous drug users, four are the children of drug users and two have been infected through sexual contacts. Three patients have developed the acquired immune deficiency syndrome and at least eight have symptomatic HIV disease. Sixty per cent of Ireland's seropositive population have been infected through intravenous drug abuse but nationally only 16% of all intravenous drug users tested are seropositive; in the study practice, however, at least 35% (48/137) of known intravenous drug users are seropositive.