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It is proposed that the new American and European AIDS epidemics are caused by recreational and anti-HIV drugs rather than by human immunodeficiency virus (HIV). Chronologically, the AIDS epidemic in the 1980s followed a massive escalation in the consumption of recreational drugs that started in the 1960s and 70s. Epidemiologically, both epidemics derive about 80% of their victims from the same groups of 20-44 year-olds, of which 90% are males. In America 32% of these are intravenous drug users and their children, about 60% are male homosexuals who are long-term users of oral aphrodisiac drugs and an unknown percentage are prescribed the cytotoxic DNA chain terminator AZT, as inhibitor of HIV. Direct evidence indicates that these drugs are necessary for HIV-positives and sufficient for HIV-negatives to develop AIDS diseases. The drug-AIDS hypothesis predicts correctly that: (i) AIDS is new in the US, because the drug epidemic is new, while the HIV epidemic is old--fixed at a constant 1 million Americans since 1985; (ii) despite an increase in venereal diseases, AIDS remains restricted to long-term drug users and small groups with clinical deficiencies; (iii) over 72% of AIDS occurs in 20-44 year-old males, because they make up over 80% of hard psychoactive drug use; (iv) distinct AIDS diseases correlate with the use of distinct drugs, eg Kaposi's sarcoma with nitrite inhalants, tuberculosis with intravenous drugs, and leukopenia, anemia, and nausea with AZT; (v) AIDS diseases are only acquired after long-term drug consumption, rather than after single contacts as the virus-hypothesis predicts. The drug hypothesis can be tested epidemiologically and experimentally in animals. It predicts that most AIDS can be prevented by stopping the consumption of drugs, and provides a rational basis for therapy.
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PMID:The role of drugs in the origin of AIDS. 142 Oct 32

We used an endoscopic method of quantification to evaluate the response of symptomatic gastrointestinal Kaposi's sarcoma (KS) prospectively in seven patients with acquired immune deficiency syndrome (AIDS) who were participating in chemotherapy trials for extensive cutaneous KS. The sums of the diameters of KS lesions in the esophagus, stomach, duodenum, and distal colon were used as a measure of extent of disease. Intravenous therapy [adriamycin/bleomycin/vincristine (N = 5), adriamycin (N = 1), or bleomycin/vincristine (N = 1)] was given every 2 wk for a mean of six cycles. Five of seven patients (71%) had a cutaneous response, whereas 9/15 (60%) gastrointestinal sites showed a remission. Sites of complete response all had an initial sum of lesion diameters less than or equal to 30 mm. Five of five patients with duodenal KS responded (3/5 complete), whereas just two partial responses were seen in five patients with gastric KS (4/5 with duodenal KS had sums of diameters less than or equal to 20 mm, whereas 4/5 with gastric KS had sums greater than or equal to 150 mm). Symptoms (abdominal pain, nausea/vomiting, hematemesis, diarrhea) resolved in all patients within two cycles of therapy. In summary: 1) the response rate of gastrointestinal KS to chemotherapy is similar to that of cutaneous KS; 2) the best response is seen in patients with less extensive disease and duodenal involvement; and 3) symptoms of gastrointestinal KS respond to chemotherapy even if the KS lesions do not resolve.
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PMID:The response of symptomatic gastrointestinal Kaposi's sarcoma to chemotherapy: a prospective evaluation using an endoscopic method of disease quantification. 169 12

In a series of studies, recombinant interferon-alpha 2a (rIFN alpha 2a, Roferon-A) was administered alone (273 men) or combined with vinblastine (91 men) to patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Patients were treated with daily doses of rIFN alpha 2a ranging from 3 to 54 million international units (I.U.) administered intramuscularly. A dose of 36 million I.U. daily for approximately 10 weeks followed by a three times weekly maintenance schedule with the same dose resulted in the best overall therapeutic benefit. An escalating-dose regimen of 3, 9, and 18 million I.U. daily, each for 3 days, followed by 36 million I.U. daily, produced equivalent therapeutic benefit with amelioration of acute toxicity in some patients. Response was more likely in patients without a history of opportunistic infection or B symptoms (fever, night sweats, or weight loss). Response rate increased with increasing baseline CD4 lymphocyte count and was 45.5% in patients with a CD4 count of greater than 400/mm3. Responding patients with a CD4 count of greater than 200/mm3 had a distinct survival advantage over patients who had similar CD4 counts but whose tumors did not regress with therapy. The addition of vinblastine increased toxicity and did not improve the response rate or prolong survival. Side effects included fatigue, fever, chills, myalgias, headaches, anorexia, nausea, diarrhea, and dizziness. Mild abnormalities in hematologic and liver function tests occurred in some patients. Most adverse effects diminished or resolved with continued therapy. We conclude that rIFN alpha 2a offers important therapeutic benefit in a select group of patients with AIDS-related KS.
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PMID:Interferon-alpha 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 182 54

Since intestinal microsporidiosis might be of importance in the pathogenesis of gastrointestinal symptoms in patients infected with HIV, we examined duodenal biopsies of HIV-infected patients by electron microscopy. Enterocytozoon bieneusi infection of the small intestine was found in one of 23 patients studied, which gives a 95% confidence interval for the prevalence rate between 0.1% and 22%. The infected patient was a 24-year-old homosexual male with AIDS who underwent upper endoscopy because of acute epigastric pain, nausea, and vomiting. These symptoms were obviously due to mesenterial Kaposi's sarcoma obstructing the duodenal passage, as was later revealed at autopsy. However, microsporidiosis might have caused the patient's eight-month history of diarrhea and weight loss, since infected cells showed signs of degeneration, and no other pathogens were ever detected in stool or biopsy. Our finding of Enterocytozoon bieneusi infection in a German AIDS patient supports the concept of a worldwide distribution of this parasite; further studies are needed to define its exact prevalence in HIV-infected patients and its pathogenic relevance.
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PMID:Intestinal microsporidiosis in a German patient with AIDS. 194 57

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.
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PMID:A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). 254 86

Twelve patients with endemic Kaposi's sarcoma (KS) were entered into a clinical trial of vincristine (VCR) infusion. Patients received 5-day courses of VCR, 0.25 mg/m2/day by continuous infusion, after an 0.5 mg intravenous bolus injection. Courses were repeated every four weeks. Stabilization of disease occurred in nine patients and could be maintained for a mean of 3 months (range: 2-7 months). Complete or partial remissions were not achieved with this protocol. Complications of therapy consisted of development of moderate neurotoxicity and paralytic ileus in one patient. Two patients developed opportunistic infections while on therapy. Hematologic toxicity, nausea or emesis did not occur. Single agent VCR by infusion is well tolerated by patients with the acquired immunodeficiency syndrome (AIDS) but appears to have only limited activity in the treatment of AIDS-related KS.
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PMID:[Monotherapy of endemic Kaposi sarcoma with long-term vincristine infusion]. 359 Aug 3

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
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PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

There are increasing challenges for the practising gastroenterologist in treating AIDS-related gastrointestinal diseases. The differential diagnoses of dysphagia and odynophagia include cytomegalovirus (CMV) and herpes simplex virus (HSV) infection, non-specific aphthous ulceration and non-AIDS oesophageal diseases, especially reflux oesophagitis. Chronic subacute abdominal pain with nausea, vomiting, early satiety and weight loss is suggestive of an obstructive lesion caused by lymphoma or Kaposi's sarcoma. Severe acute abdominal pain can indicate pancreatitis or intestinal perforation due to cytomegalovirus. Right upper quadrant pain (with or without fever, vomiting or abnormal liver function tests with a cholestatic profile) is suggestive of hepatobiliary pathology including cholecystitis, cholangitis, acalculous cholecystitis and AIDS cholangiopathy. Diarrhoea is the most common gastrointestinal symptom of AIDS, affecting 50-90% of patients. Causes of AIDS diarrhoea include protozoa (Cryptosporidium parvum, Isospora belli, Enterocytozoon bieneusi, Septata intestinalis, Cyclospora spp, Entamoeba histolytica and Giardia lamblia), bacteria (Mycobacterium avium-intracellulare, Clostridium difficile, Salmonella, Shigella and Campylobacter jejuni), and viruses (CMV, HSV and possibly HIV). Chronic diarrhoea, malnutrition and weight loss can shorten the life-span of patients with AIDS. Elemental diets, isotonic formulas, medium chain triglycerides and total parenteral nutrition have been tried with little success in AIDS patients with severe diarrhoea and wasting.
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PMID:AIDS and the gut. 805 32

Because of its unusual mechanism of action, docetaxel was selected for study in advanced soft tissue sarcomas of adults as part of a search for new active antisarcoma agents. Patients at least 18 years old with measurable histologically proven advanced nonosseous sarcomas were enrolled if they had ECOG performance status of < or = 2 and satisfactory leukocyte and platelet counts, and hepatic and renal function. Patients with Kaposi's sarcoma, mesothelioma, meningioma, embryonal rhabdomyosarcoma, and extraosseous Ewing's sarcoma were excluded, as were patients with brain or leptomeningeal metastases. Other specific contraindications to participation included other active cancer, previous or concurrent cancer chemotherapy or immunotherapy, and known allergy to the drug vehicle, polysorbate 80. Women of childbearing potential were required to have a negative pregnancy test. Following premedication with dexamethasone and diphenhydramine hydrochloride, docetaxel 100 mg/m2 as a concentrated solution containing 40 mg/ml in polysorbate 80 was infused over 1 h in 250 ml of either dextrose 5% in water or 0.9% saline. Treatment was repeated at 3-week intervals using standard definitions for objective responses. Up to two separate 25% toxicity directed dose reductions were permitted. Between May and December 1993, nine men and nine women registered (median age, 44 years). They received a total of 51 cycles of docetaxel (median, 2.5 cycles). Toxicity included moderate leukopenia (median first cycle nadir, 1.5 x 10(9)/L) but no significant thrombocytopenia. Alopecia, diarrhea, nausea, vomiting, and anorexia were common side effects. Fever, minor skin rashes, stomatitis, and edema were also observed. One drug-related death occurred in a neutropenic patient. One partial regression was observed (5.9%, 95% C.I. 0.15-28.7%) among the 17 eligible patients in a patient with metastatic uterine leiomyosarcoma.
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PMID:Phase II study of docetaxel in advanced soft tissue sarcomas. 893 74

The Food and Drug Administration (FDA) has recently granted accelerated approval to Liposome Technology, Inc., to market DOX-SL for people with AIDS with refractory Kaposi's sarcoma (KS). DOX-SL, an intravenous drug, is a new form of a regular cancer chemotherapy called doxorubicin, and has dosing schedules similar to standard chemotherapy. The drug, encapsulated in lipid membranes (liposomes), will enable doxorubicin to be delivered directly in a higher concentration to KS lesions, with fewer systemic side effects. The drug will likely be used in combination with standard chemotherapy. Side effects include: hair loss, nausea, and neutropenia. This is the first time the FDA has ever approved a drug for KS.
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PMID:KS update. 1136 82


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