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Biomedical subjects

H Jablonowski

Publications and source records attributed to H Jablonowski.

At least 73 records · Page 4Linked to original sources

A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

AIDS-Related Complex↗

Studies of zidovudine in combination with didanosine and zalcitabine.

A number of antiviral agents have been developed to treat individuals with HIV infection. Monotherapy treatment with the licensed reverse transcriptase (RT) inhibitors zidovudine (AZT), zalcitabine (ddC), and didanosine (ddI) has been shown to delay disease progression in the short term. However, after prolonged treatment viral resistance to these agents emerges. To overcome this development of resistance and subsequent destruction of the immune system leading to disease progression, combination therapies of two or more RT inhibitors have been investigated. In the past, studies have demonstrated that the antiviral drugs ddI and ddC have overlapping toxicities and show cross-resistance. Together, therefore, they are unlikely to prove successful as combination therapy. Conversely, AZT and ddI, and AZT and ddC, have additive or synergistic activities. Recent clinical trials have shown that these two combination therapies are well tolerated and are more effective than monotherapy in delaying the progression of HIV disease. Data from these studies suggest that the maximal benefit from combination therapies can be derived only if they are initiated early in the course of infection, e.g., when CD4 counts are greater than 150 cells/mm3. In clinical studies, AZT/ddI in combination, tended to have a more positive effect on CD4 cell count than the AZT/ddC combination, although the difference was statistically significant only when baseline CD4 count was greater than 100 cells/mm3. No serious side effects have been observed with either combination therapy (AZT/ddC or AZT/ddI) although not surprisingly, patients receiving ddI were more likely to suffer gastrointestinal side effects and those receiving ddC were more likely to suffer from peripheral neuropathy.

Antiviral Agents↗

[HIV infection and the lower gastrointestinal tract--characteristics of endoscopic diagnosis].

In the course of HIV infection intestinal complaints, particularly diarrhoea, are frequent. As a result of the HIV-induced immunosuppression infections with unusual viral, mycobacterial and protozoan pathogens occur. In addition usually self-limiting intestinal infections become frequently persistent in HIV-positive patients with advanced cellular immunodeficiency. Intestinal manifestation of HIV-associated neoplasm is not rare. In combination with microbiological examination of stool specimen endoscopy of the lower gastrointestinal tract is a valuable diagnostic method, especially for the diagnosis of viral infections and neoplasm.

AIDS-Related Opportunistic Infections↗

[HIV infection: findings in liver and bile ducts].

Gastrointestinal diseases in HIV-infected patients mainly affect the bowel, the oesophagus, and the liver. Most of the hepatic diseases are due to opportunistic infections and associated to AIDS. In the advanced AIDS disease Mycobacterium avium intracellulare is the most frequent bacterial infections agent. Mycobacterium tuberculosis is often diagnosed in less immunocompromised patients. Viral hepatitis (A, B, C, D) is more often diagnosed in HIV-infected patients than in non-infected controls. Non-Hodgkin's lymphoma of the liver is a relatively frequent tumour in HIV-infected patients. Kaposi's sarcoma may also affect the liver. Infections with the cytomegalovirus or cryptococci mainly affect the biliary system causing acalculous cholecystitis or secondary sclerosing cholangitis. In addition to clinical and laboratory diagnostics sonographic and computer tomographic examinations are important. The diagnostic power of sonographic and computer tomographic examinations can be increased by guided biopsies. Biliary diseases can be diagnosed by retrograde endoscopic diagnostic investigations (ERC, ERCP). This overview resumes the most important diagnostic and differential diagnostic data in HIV-associated liver and biliary tract diseases.

AIDS-Related Opportunistic Infections↗

The use of intravenous immunoglobulins in symptomatic HIV infection. Results of a randomized study.

To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.

AIDS-Related Opportunistic Infections↗

A pathologically distinct new form of HIV associated encephalopathy.

We present the clinical, morphological and neuropathological findings in a 44-year-old male suffering from the acquired immunodeficiency syndrome (AIDS) (CDC stage IV C2) who presented with rapidly progressive right-side hemiparesis and developed hemianopia and aphasia. Scans showed multiple, not contrast-enhancing, not space-occupying echo-intensive lesions in T2-weighted MR-imaging. No hint for an opportunistic infection, necrotizing vasculitis or vascular disease was found. All therapeutic regimens failed and 8 weeks after onset of neurological symptoms the patient died because of cardiorespiratory arrest. Post-mortem examination excluded opportunistic infection, progressive multifocal leukoencephalopathy, lymphoma, vasculitis and ischemia of the brain. In the presence of an unusually high amount of HIV-infected macrophages at immunohistochemical examination, the overall pathological findings were atypical both for HIV encephalitis and HIV leukoencephalopathy. We describe a pathologically distinct new form of HIV associated encephalopathy.

AIDS Dementia Complex↗

Serum and cerebrospinal fluid levels of soluble intercellular adhesion molecule 1 (sICAM-1) in patients with HIV-1 associated neurological diseases.

We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1) in paired serum and CSF samples of 110 HIV-1-positive patients with and without neurological symptoms and 40 HIV-negative non-immune neurological controls, and in sera of 26 asymptomatic HIV-1-positive patients. Serum sICAM-1 levels in asymptomatic HIV-1-positive patients were significantly increased in comparison to HIV-negative controls. Moreover, they were significantly higher in HIV-1-positive patients with AIDS-defining diseases than in the asymptomatic HIV-1-positive group. In subgroups of patients with neurological disease, the highest serum values were found in HIV encephalopathy. CSF levels of sICAM-1 were elevated only in HIV-1-positive patients with neurological disease mainly due to passive diffusion through a defective blood-brain barrier. An sICAM-1 index was calculated as a measure for intrathecal production of sICAM-1 but showed no significant differences between patients with and without neurological involvement. However, increased levels of the sICAM-1 index were found in some patients with opportunistic CNS infection of bacterial or fungal origin. Serum and CSF levels of sICAM-1 correlated with neopterin levels, a marker of interferon-gamma-mediated macrophage activation and CSF sICAM-1 levels were inversely correlated to numbers of CD4+ T cells. Elevated serum sICAM-1 levels already in asymptomatic HIV-1-positive individuals add to the evidence for an early immune activation in HIV infection. With the further increase of serum and CSF s-ICAM-1 in patients with AIDS-defining diseases sICAM-1 could serve as a new surrogate marker similar to neopterin.

AIDS Dementia Complex↗

Effects of Helicobacter pylori on histamine and carbachol stimulated acid secretion by human parietal cells.

Helicobacter pylori (H pylori) infection is associated with hypo, normal, and hypersecretory disorders of the gastric mucosa. Pathophysiological pathways by which H pylori interacts with acid secretion are still unclear. The effects of H pylori on (14C) aminopyrine uptake by human parietal cells were examined as an indirect assay for acid secretion. Isolated oxyntic glands were stimulated with submaximal concentrations of histamine or carbachol and incubated with sonicates of different H pylori strains. Omeprazole and sonicates of Campylobacter jejuni served as positive and negative controls, respectively. Two of four H pylori strains reduced hydrochloric acid sequestration within the parietal cells significantly and in a dose dependent manner in up to 80%. Interaction with acid secretion may therefore constitute a factor contributing to a distinct pathogenicity of H pylori strains.

Aminopyrine↗

Effect of Helicobacter pylori on dbc-AMP stimulated acid secretion by human parietal cells.

This study examines the effect of different H.p. strains (A-D) on dbc-AMP stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p. strains B and C had little or no effect. We conclude that H.p. strains vary in their ability to suppress acid secretion, and that the site of inhibition lies beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal cell. Interference with acid secretion may facilitate H.p. colonization of the stomach and may prove to be an important pathogenetic factor.

Aminopyrine↗

[Visceral leishmaniasis with gastrointestinal involvement in a 30-year-old HIV infected patient].

We report the case of a 30-years old HIV-infected woman who suffered from recurrent fever up to 41 degrees C, loss of appetite, loss of 8 kg body weight and swelling of the cervical and inguinal lymph nodes. The diagnostic work-up revealed infection with leishmania in gastric and duodenal biopsies. The parasites were also found in the inguinal lymph nodes and in the bone marrow of the patient. According to patient's history the infection was acquired on a holiday in southern spain. The patient was treated with pentavalent antimony in combination with interferon gamma. Visceral leishmaniosis in immuno-suppressed patients is discussed and therapeutic approaches are described.

AIDS-Related Opportunistic Infections↗

[Sclerosing cholangitis with papillary stenosis in an HIV-infected patients with Cryptosporidium infection].

We report the case of a 46-year old HIV-infected patient who suffered from severe recurrent diarrhoea for 18 months. In stool cultures cryptosporidiae were identified. The cryptosporidial enteritis was unresponsive to therapy. In the further course of cryptosporidial infection the patient developed HIV-associated cholangitis with increasing upper abdominal pain, progredient laboratory cholestasis and morphological changes indicating posthepatic cholestasis. Papillary stenosis with erosive papilitis caused by cryptosporidia was diagnosed. Sphincterotomy significantly improved the clinical status of the patient. Cholangitis with associated crytosporidial infection in a HIV-infected patient ist discussed and necessary diagnostic and differential therapeutic approaches are described.

AIDS-Related Opportunistic Infections↗

Rhodococcus equi pneumonia in an HIV-infected patient.

We report a case of a 46-year-old HIV-infected patient suffering Rhodococcus equi pneumonia and septicaemia. After the failure of an initial antibiotic treatment, the upper lobe of the right lung was resected due to a cavitating pneumonia. After that the patient stabilized for a period of 7 months by administration of a resistogram-adapted combination of tetracycline, erythromycin and clindamycin. Due to the patient's decision, antibiotic treatment was stopped when a cytomegalovirus retinitis was diagnosed. Six weeks later new pulmonary infiltrations were diagnosed and a Rhodococcus equi bacteraemia evolved. The patient died one year after the first diagnosis of the Rhodococcus equi infection. The present case suggests that the infection with Rhodococcus equi in patients with advanced HIV infection demands permanent antibiotic prophylaxis.

AIDS-Related Opportunistic Infections↗

Acoustically evoked event-related potentials in HIV-associated dementia.

Cognitive event-related potentials (ERPs) were recorded in 33 HIV-positive individuals with clinical signs of dementia (group C) using an auditory oddball paradigm, in comparison to a healthy control group of comparable education and social environment (group A) and to a cohort of clinically asymptomatic HIV-positive individuals (group B). Parameters evaluated were: N1, P2, N2 and P3 latencies and N1-P2, P2-N2 and N2-P3 amplitudes. Results of group B and C were correlated with clinical findings, test psychometric performance and standard EEG records of both groups. The demented patients revealed significant prolongations of N2 and P3 peak latencies or complete abolition of these "endogenous," not stimulus-related, ERP peaks. Clinical bradykinetic symptoms and time-dependent psychometric abilities correlated with N2 and P3 latency prolongations and with the general slowing of the alpha rhythm, indicating an involvement of cortical and subcortical structures in HIV-related brain disease.

AIDS Dementia Complex↗

[The prevention of Pneumocystis carinii pneumonia by pentamidine inhalation].

167 HIV-positive patients (155 men, 12 women; mean age 31 [18-61] years) with CD4 lymphocyte counts below 250/microliter every 4 weeks received 300 mg pentamidine per aerosol inhalation during out-patient visits, as prophylaxis against Pneumocystis carinii. 89 patients were clinically in the AIDS stage and 33 in the AIDS-related complex (ARC) stage. 29 patients had a lymphadenopathy syndrome, while 16 were asymptomatic. 130 patients received primary prophylaxis, while 37 who had previously had an attack of Pneumocystis carinii pneumonia were given pentamidine as secondary prophylaxis. During a mean observation period of 8 months three patients developed Pneumocystis carinii pneumonia (1.7%): their CD4 lymphocyte count was under 20/microliters. Pentamidine inhalation reduced the incidence of a first attack of pneumonia to 0.18% per month and recurrence to 0.32% per month. These figures confirm the great effectiveness of primary and secondary prophylaxis with pentamidine inhalation.

AIDS-Related Complex↗

Magnetic stimulation of motor cortex in relation to fastest voluntary motor activity in neurologically asymptomatic HIV-positive patients.

Forty-two HIV-positive patients of various CDC stages without clinically evident neurological deficits were examined with transcranial magnetoelectrical stimulation (TMS). Cortical as well as cervical and lumbar root stimulation was performed after excluding peripheral neuropathies in comparison to an age- and sex-matched control group. Whereas central conduction times were normal, conduction between cervical or lumbar roots and muscle was prolonged. Results were correlated to those of a motor test battery, which revealed slowing of fast alternating movements similar to findings in extrapyramidal disorders. Data indicate that proximal parts of the peripheral nervous system and extrapyramidal structures are subclinically involved in early HIV infection whereas the fastest corticospinal projections remain intact.

Adult↗