Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pneumocystosis, the most common opportunistic infection associated with the acquired immunodeficiency syndrome, is usually restricted to the lungs and results in severe bilateral pneumonia, which is fatal unless vigorously treated. Rare cases have been reported in which involvement of other organs or disseminated disease occurred in addition to the pulmonary lesions. Pentamidine, an efficient drug used intravenously for the treatment of pulmonary pneumocystosis, has also recently been used in aerosolized form for the prevention of Pneumocystis infection in patients with the acquired immunodeficiency syndrome. In the present case, widely disseminated, though symptomless, pneumocystosis developed in a human immunodeficiency virus-positive individual treated prophylactically with aerosolized pentamidine. Despite heavy multiorgan infection with Pneumocystis carinii, the lungs revealed no microorganisms or characteristic inflammatory lesions. This case indicates that aerosolized pentamidine, while efficient against the pulmonary infection, may not produce fungicidal blood levels sufficient for the prevention of disseminated pneumocystosis.
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PMID:Disseminated pneumocystosis without pulmonary involvement during prophylactic aerosolized pentamidine therapy in a patient with the acquired immunodeficiency syndrome. 174 32

Involvement of the pancreas by human immunodeficiency virus (HIV) infection has not been adequately addressed and is the object of this review. I analyzed the English language literature, including single case reports of pancreatic involvement and larger series reporting detailed pathological findings of patients with HIV infection. Nonspecific pathological changes in the pancreas are frequently seen at autopsy of HIV-infected patients, but are not more common than in controls. Several types of infections (mainly cytomegalovirus, Cryptococcus neoformans, and Mycobacteria) and neoplasms (lymphoma and Kaposi's sarcoma) can involve the pancreas because they are usually disseminated. Although the serum amylase may be elevated, the patient remains asymptomatic. Occasional instances of severe and even fatal pancreatitis have been reported with HIV infections and attendant drug toxicity. Pentamidine has a predictable incidence of hypoglycemic episodes and 2',3'-dideoxyinosine provokes pancreatitis in a minority of treated patients. Such drug toxicity seems to deserve greater clinical concern than opportunistic infections or neoplasms.
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PMID:Pancreatic involvement in human immunodeficiency virus infection. 200 47

Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients who were diagnosed by the aspiration-lung-biopsy. They were treated with 4 mg/kg of pentamidine isethionate intravenously administered followed by pentamidine aerosol inhalation. Although clinical and laboratory findings were improved by the fifth or seventh day of intravenous therapy, substantial leukocytopenia, from 3,000/cmm to 600/cmm and from 2,700/cmm to 1,000/cmm, occurred. At this point, the method of pentamidine administration was switched to inhalation. Pentamidine 600 mg in 30 ml distilled water was aerosolised using ultrasonic nebuliser and exposed for a 30-minute period once daily. In both cases, chest x-rays showed improvements: The disappearance of P. carinii were obtained in two weeks. Mild coughing was the sole adverse reaction encountered during the course of aerosol inhalation.
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PMID:Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients: supplemental treatment with aerosolised pentamidine isethionate. 278

The study compared the pulmonary deposition of nebulised pentamidine when inhaled by way of different nebuliser systems by nine human-immunodeficiency-virus-positive patients with a history of previous Pneumocystis carinii pneumonia. Pentamidine, 50 mg or 300 mg, mixed with technetium-99m-labelled human serum albumin in a total volume of 3 ml, was administered by way of three jet nebulisers (System 22', 'System 22 Mizer', and 'Respigard II') operated with a gas flow of 6 l/min, and one ultrasound nebuliser ('Pulmosonic'). Pulmonary and non-pulmonary isotope deposition was measured for each apparatus and adverse effects and lung function tests were recorded. For both doses of pentamidine, the system 22 mizer produced the largest pulmonary isotope deposition and it was completed in the shortest time. Oropharyngeal and gastric deposition were least with the respigard II, which also caused the fewest adverse effects. The adverse effects were greatest with the system 22 mizer and pulmosonic and the higher pentamidine dose, which also caused significant reductions in measurements of pulmonary function. It is concluded that either the system 22 mizer or the respigard II should be used to administer nebulised pentamidine.
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PMID:Differences in relative efficiency of nebulisers for pentamidine administration. 290 8

Pentamidine is known to cause severe dysglycaemia by damaging beta-cell function of the pancreas. The exact mechanism still remains unclear. We report the case of a 53-year-old man infected with the human immunodeficiency virus who developed insulin-dependent permanent diabetes mellitus 3 days after starting intravenous treatment with pentamidine for pneumocystis carinii pneumonia. Discharged from hospital the daily need of insulin increased continuously over one year now requiring an average dose of 80 units per day. So far, a number of cases of insulin-dependent diabetes mellitus following pentamidine therapy has been reported, but long-term observations are rare.
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PMID:Insulin-dependent diabetes mellitus following pentamidine therapy in a patient with AIDS. 771 9

A study was conducted to determine the intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine prophylaxis (APP) in patients infected with human immunodeficiency virus (HIV). 151 patients received high-dose (300 mg twice a month or 600 mg once a month) APP as part of a previously published clinical trial, and 29 additional patients received standard-dose (300 mg once a month) APP. Serial blood samples were obtained from the first cohort: 577 samples were obtained from 76 patients in the group given 600 mg once a month, and 554 blood samples were obtained from 75 patients in the group given 300 mg twice a month. In 9 of the 151 patients, bronchoscopy and tri-lobar (right upper, middle, and lower lobe) bronchoalveolar lavage (BAL) were performed 6 and 12 months after initiation of APP. Unilobar (right middle lobe) BAL was performed in the 29 patients infected with HIV who underwent bronchoscopy for diagnostic purposes. Pentamidine was measured using a chromatographic (HPLC) assay. The concentrations (mean +/- SD) of pentamidine in plasma in the groups given 300 mg twice a month and 600 mg once a month were 5.3 +/- 6.1 ng/mL and 8.8 +/- 9.6 ng/mL, respectively, and accumulation did not occur. The BAL supernatant and alveolar cell pentamidine concentrations were not significantly different in the 3 lobes and ranged from 16.5 +/- 7.7 ng/mL to 29.2 +/- 19.5 ng/mL and 1255 +/- 1142 ng/mg protein to 1572 +/- 1161 ng/mg protein in the group given 300 mg twice a month; and from 5.5 +/- 2.9 ng/mL to 9.4 +/- 7.7 ng/mL and 339 +/- 201 ng/mg protein to 571+/- 681 ng/mg protein in the group given 600 mg once a month. The intropulmonary concentrations of pentamidine at 6 and 12 months were not significantly different. In 18 of the 29 patients who received 1 to 7 prior monthly doses of standard APP, drug concentrations in BAL increased linearly (y = 2.05x) with the number of doses administered before bronchoscopy. These data indicate that intrapulmonary drug concentrations continue to increase for approximately 6 months after the initiation of APP, at which time steady state is achieved, and that administration of high dose APP is probably safe.
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PMID:Intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine used for prophylaxis of pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus. 875 Mar 67

1. Pentamidine is routinely used to reduce the incidence of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus, but it has been described as inducing pulmonary adverse effects, such as cough and bronchospasm. 2. In this paper we have investigated the effects of pentamidine on guinea-pig isolated main bronchi and human isolated bronchi. Pentamidine induced a concentration-dependent contraction in both preparations with pD2 values of 9.64 +/- 0.07 (n = 8) and 9.73 +/- 0.06 (n = 8) and a maximal effect (Emax) of 40 +/- 4% and 34 +/- 5% of the response to acetylcholine (1 mM) in guinea-pig and human bronchi respectively. Atropine (0.01 to 0.1 microM) and the muscarinic M3 receptor antagonist, hexahydro-siladiphenidol (0.1 and 1 microM) inhibited pentamidine-induced concentration-responses in both preparations in a non-competitive manner, whereas only high concentrations of the M1 receptor antagonist pirenzipine (1 microM) inhibited pentamidine concentration-response curves. 3. The cholinesterase inhibitor, tacrine (1 microM), potentiated the effect of pentamidine; in contrast, morphine inhibited pentamidine-induced responses. 4. The bronchoconstrictor effect of pentamidine on guinea-pig and human isolated bronchi was not modified by the H1 histamine receptor antagonist, mepyramine, by indomethacin or by the neurokinin NK1 and NK2 receptor antagonists, CP-96,345 and SR 48969 respectively, suggesting that neither histamine receptor stimulation, arachidonic acid derivative formation, nor tachykinin release are involved in pentamidine-induced contraction of human and guinea-pig airways. 5. Our overall results suggest that pentamidine induces contraction of guinea-pig and human isolated bronchi through prejunctional cholinergic nerve stimulation.
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PMID:Indirect muscarinic receptor activation by pentamidine on airway smooth muscle. 893 15

The current interest in leishmaniasis stems from the importance of this disease with respect to travel medicine, veterans of Operation Desert Storm, humanitarian concerns, and infection with human immunodeficiency virus. Herein, I review aspects of leishmaniasis that are of practical value to practitioners, including presentation, diagnosis, and chemotherapy; I will emphasize advances in chemotherapy over the last 10 years. Amphotericin B and its new lipid formulations are now competitive with pentavalent antimony as primary therapy for visceral leishmaniasis. Pentamidine, paromomycin, and adjunctive therapy with interferon-gamma are secondary regimens for the treatment of this condition. High-dose long-term regimens of antimony have been shown to be highly effective for the treatment of cutaneous leishmaniasis. Preliminary evidence of efficacy has been observed with short courses of pentamidine for the treatment of Leishmania braziliensis complex disease and topical paromomycin/methylbenzethonium chloride for the treatment of Leishmania major disease.
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PMID:Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. 914 44

In this review, both cationic and neutral synthetic ligands that bind in the minor groove of DNA are discussed. Certain bis-distamycins and related lexitropsins show activities against human immunodeficiency virus (HIV)-1 and HIV-2 at low nanomolar concentrations. DAPI binds strongly to AT-containing polymers and is located in the minor groove of DNA. DAPI intercalates in DNA sequences that do not contain at least three consecutive AT bp. Berenil can also exhibit intercalative, as well as minor groove binding, properties depending on sequence. Furan-containing analogues of berenil play an important role in their activities against Pneumocystis carinii and Cryptosporidium parvuam infections in vivo. Pt(II)-berenil conjugates show a good activity profile against HL60 and U-937 human leukemic cells. Pt-pentamidine shows higher antiproliferative activity against small cell lung, non-small cell lung, and melanoma cancer cell lines compared with many other tumor cell lines. trans-Butenamidine shows good anti-P. carinii activity in rats. Pentamidine is used against P. carinii pneumonia in individuals infected with HIV who are at high risk from this infection. A comparison of the cytotoxic potencies of adozelesin, bizelesin, carzelesin, cisplatin, and doxorubicin indicates that adozelesin is a potent analog of CC-1065. Naturally occurring pyrrolo[2,1-c][l,4]benzodiazepines such as anthramycin have a 2- to 3-bp sequence specificity, but a synthetic PBD dimer spans 6 bp, actively recognizing a central 5'-GATC sequence. The crosslinking efficiency of PBD dimers is much greater than that of other major groove crosslinkers, such as cisplatin, melphalan, etc. Neothramycin is used clinically for the treatment of superficial carcinoma of the bladder.
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PMID:Synthetic DNA minor groove-binding drugs. 1058 Aug 32

Visceral leishmaniasis is present in 61 countries but 90% of the 500,000 new cases that arise annually occur in five countries, i.e., India, Bangladesh, Nepal, Sudan, and Brazil. Annual mortality is approximately 59000 cases. Agents based on pentavalent antimony have been the mainstay of treatment for the last 60 years. In recent years, however, clinical resistance to these agents has been reported especially in the state of Bihar in India. Pentamidine and amphotericin B were introduced in the 1950s and 1960s. More recent additions to the therapeutic arsenal include liposomal amphotericin B, miltefosine, and paromomycin. Among these recent molecules, miltefosine, i.e., the only oral agent, appears most vulnerable because it involves long-term treatment and has a long half-life. The main therapeutic problems now being encountered are the emergence of acquired resistance to antimonials, the high cost of treatment, and failure of therapy in immunocompromised patients mainly due to concurrent human immunodeficiency virus (HIV) infection. For eradication initiatives such as the one aimed at eliminating leishmaniasis on the Indian subcontinent, the appearance of drug resistance increases the risk associated to parasite infection and, as for malaria, tuberculosis and HIV infection, raises fears that the problems in the implementation of public health policies will lead to highly refractory forms.
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PMID:[Visceral leishmaniasis: clinical sensitivity and resistance to various therapeutic agents]. 1847 81


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