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Biomedical subjects

H Jablonowski

Publications and source records attributed to H Jablonowski.

At least 55 records · Page 3Linked to original sources
PubMed1997

Induction of granulocyte colony-stimulating factor by acute febrile infection but not by neutropenia in HIV-seropositive individuals.

The objective of this study was to assess endogenous granulocyte colony-stimulating factor (G-CSF) serum levels in HIV-seropositive individuals with persistent neutropenia or acute febrile infection. Serum levels of G-CSF were measured by enzyme-linked immunoabsorbent assay. HIV-seropositive subjects (n = 28) with afebrile neutropenia (< 1000 neutrophils/microliter) showed low G-CSF serum levels (i.e., median was below the detection limit) not different from those of healthy volunteers (n = 66) or nonneutropenic HIV-seropositive controls (n = 75). In contrast, patients with acute myeloid leukemia and afebrile neutropenia from chemotherapy (n = 17) demonstrated markedly elevated G-CSF levels (median, 264 pg/ml; p < 0.0001). However, HIV-seropositive patients with pneumonia (n = 17) showed increases of G-CSF serum levels (median, 152 pg/ml; p < 0.0001) similar to HIV-seronegative patients (n = 17) with pneumonia (median, 123 pg/ml; p = 0.97). The results suggest that there may be a contribution of low G-CSF serum levels to persistent neutropenia in HIV-seropositive individuals. Moreover, the different G-CSF serum levels in HIV-seropositive individuals in response to neutropenia or acute febrile inflammation suggest different mechanisms for the regulation of G-CSF.

Acute Disease↗
PubMed1997

Diagnostic criteria and clinical procedures in HIV-1 associated progressive multifocal leukoencephalopathy.

The diagnosis of definite progressive multifocal leukoencephalopathy (PML) has been a neuropathological domain. We reviewed all Human Immunodeficiency Virus Type 1 (HIV-1) seropositive patients in our institution between 01.01.1989 and 31.12.1994 and identified 20/823 cases with PML by clinical and imaging criteria. Diagnosis was neuropathologically confirmed in 5 cases. Diagnostic criteria included rapid onset (< 2 weeks) of multifocal neurological signs and symptoms, advanced immunosuppression and asymmetric uni- or multifocal white matter lesions without mass effect, contrast enhancement or cortical atrophy in magnetic resonance imaging (MRI). The overall incidence of PML was stable over the observation period (approximately equal to 2.5%). The mean age at onset (41.7 years) was significantly lower compared to HIV-1 seronegative PML patients (peak in the sixth decade of life), male patients prevailed (100%). Mean survival (3.9 months) was extremely short. Human polyoma virus JC (JCV) polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) demonstrated a considerable rate of possible cerebral co-infection with HIV-1 and JCV as well as subclinical infection with JCV. Therefore demonstration of JCV deoxyribonucleic acid by PCR in the CSF alone is not sufficient for clinical PML diagnosis. We present diagnostic criteria on the basis of epidemiological, neuroradiological and CSF parameters that allow us to make the clinical diagnosis of PML. Although quick and safe, routine stereotactic brain biopsy is not necessary to confirm the diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Limited value of PCR for detection of Toxoplasma gondii in blood from human immunodeficiency virus-infected patients.

Cerebral toxoplasmosis is a common, opportunistic, and often life-threatening disease in HIV-infected patients. Diagnosis is supported mainly by clinical evidence and computerized tomography or magnetic resonance imaging scans, but brain images may share features with other brain diseases occurring in HIV-infected patients. To determine the diagnostic value of PCR for the detection of Toxoplasma gondii in blood from HIV-infected patients, we examined 89 blood samples from 59 HIV-infected patients. PCR and Southern blot hybridization were done with DNA extracted from blood samples from 20 patients with confirmed cerebral toxoplasmosis and from 10 patients with suspected but not confirmed cerebral toxoplasmosis. The samples were taken before and 7 to 10 days after the beginning of antiparasitic therapy. For 9 patients who suffered from cerebral toxoplasmosis more than 6 months prior to the study and for 20 patients without any evidence for toxoplasmosis only one blood sample per patient was examined. PCR gave positive results with 5 of the 20 blood samples from patients who suffered from cerebral toxoplasmosis. After 7 to 10 days of therapy PCR results became negative in all these five cases. No amplification was seen with DNA from blood samples from the other 54 patients as the target. The results presented here show that PCR testing of blood samples from HIV-infected patients is of limited value for the diagnosis of cerebral toxoplasmosis. The sensitivity was only 25%, but the specificity was very high (100%), so this technique may be useful for discriminating between cerebral toxoplasmosis and other brain diseases which may be mistaken for toxoplasmosis.

HIV Infections↗
PubMed1997

Ancillary benefits of Mycobacterium avium-intracellulare complex prophylaxis with clarithromycin in HIV-infected patients.

Because of the significant morbidity and mortality associated with opportunistic infections, prophylaxis has become routine practice in the management of immunocompromised patients such as those with AIDS. Clarithromycin, an antimicrobial agent with a broad spectrum of activity against most common respiratory pathogens as well as many protozoa, has proven to be effective for both treatment and prophylaxis of Mycobacterium avium-intracellulare complex (MAC) infection in AIDS patients. Results of a large multinational placebo-controlled study suggest that clarithromycin for MAC prophylaxis provides additional benefits. In this study, clarithromycin statistically significantly reduced the incidence of Pneumocystis carinii pneumonia (5.3% of clarithromycin recipients vs 10.0% of placebo recipients; p = 0.021), community-acquired pneumonia (7.1 vs 13.0%; p = 0.010), Giardia lamblia infection (0.9 vs 2.9%; p = 0.048), and neoplastic diseases (1.8 vs 4.1%; p = 0.010) in AIDS patients with CD4+ counts of < or = 100 cells/microliter.

AIDS-Related Opportunistic Infections↗
PubMed1997

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.

AIDS-Related Opportunistic Infections↗
PubMed1996

Combination therapy with ZDV + DDI versus ZDV + DDC in patients with progression of HIV-infection under treatment with ZDV.

HIV-seropositive patients (n = 67) who had tolerated zidovudine for at least 24 weeks and deteriorated clinically or immunologically within 12 weeks prior to study entry were allocated in an alternating manner to didanosine chewable tablets (400 mg/day) plus zidovudine (500 mg/day) or dideoxicytidine capsules (2.25 mg/day) plus zidovudine (500 mg/day). The combination of didanosine and zidovudine resulted in a more pronounced increase of CD4 cells over time compared to the combination of dideoxicytidine with zidovudine (p < 0.002). The increase of CD4 cells was almost exclusively due to patients with more than 100 CD4 cells/microliters. Clinical end points (death, AIDS-defining disease, CDC IV event) were less frequent under didanosine plus zidovudine but failed to reach statistical significance (p = 0.07). For didanosine plus zidovudine the median time on medication during study was shorter (63% vs. 100%, p < 0.05) and the number of patients discontinuing medication prematurely due to side effects was higher (59% vs. 30%, p < 0.02). The present study favors the combination of didanosine and zidovudine in patients deteriorating while receiving zidovudine for > 24 weeks in respect to the time course of the CD4 cells. In this small sized study, there seemed to be fewer clinical events in patients on the didanosine combination compared to the combination with dideoxicytidine; however, this trend failed to reach statistical significance and needs therefore to be substantiated by larger studies. However, the lower compliance of the patients may hamper the efficacy of didanosine.

Adult↗
PubMed1996

Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. The International SL-DOX Study Group.

The utility of current chemotherapeutic regimens in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) is often compromised by both limited efficacy and substantial toxicity. Pegylated (Stealth) liposomal doxorubicin hydrochloride (SL-DOX) has been demonstrated specifically to deliver high concentrations of doxorubicin to Kaposi's sarcoma (KS) lesions. This phase II study was performed to evaluate the efficacy and safety of SL-DOX in the treatment of moderate to severe AIDS-KS. Patients were treated biweekly with 10, 20, or 40 mg m-2 SL-DOX. Tumour response was assessed according to AIDS Clinical Trials Groups (ACTG) criteria before each cycle. Best response was determined for 238 patients and was achieved after a mean of 2.3 cycles (range 1-20). Fifteen patients (6.3%) had a complete response to SL-DOX, 177 (74.4%) had a partial response, 44 (18.5%) had stable disease and two (0.8%) had disease progression. SL-DOX was well tolerated: ten patients discontinued therapy because of adverse events, in four cases because of neutropenia. Grade 3 or 4 neutropenia occurred after 281 of 2023 cycles (13.9%) but involved 137 of 240 patients (57.1%) for whom data were available. SL-DOX has substantial activity in AIDS-KS. Best response is typically seen after fewer than three cycles of chemotherapy and in some cases may be prolonged. The most important adverse event is neutropenia, which occurs after a minority of cycles but which may occur in over half of all patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Synergistic stimulatory effects of tumour necrosis factor alpha and interferon gamma on replication of human immunodeficiency virus type 1 and on apoptosis of HIV-1-infected host cells.

Differential and sometimes contradictory effects have been described for tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) on replication of human immunodeficiency virus type 1 (HIV-1). The authors examined individual and coordinate action of these cytokines on HIV-1 expression, and on apoptosis of HIV-1-infected host cells by determination of reverse transcriptase activity in cell culture supernatant, expression of HIV-1-RNA and production of p24 antigen in the promonocytic cell line U937 and its persistently HIV-1-infected clone U1. Apoptosis was demonstrated by typical cleavage of cellular DNA at internucleosomal regions in promonocytic and T-lymphocytic cell lines. TNF-alpha alone markedly stimulated HIV-1 replication in U1 cells at the transcriptional and on the translational level. Exclusive application of IFN-gamma only slightly enhanced HIV-1 expression, whereas it synergistically potentiated stimulatory effects of TNF-alpha. Both cytokines also synergistically induced apoptosis in HIV-1-infected host cells. Co-ordinate action of TNF-alpha and IFN-gamma is suggested to represent an important mechanism for disease progression in HIV infection. These findings demonstrate that cytokine effects on viral expression may vary depending on their single or combined application.

Apoptosis↗
PubMed1996

Sulfadiazine-associated nephrotoxicity in patients with the acquired immunodeficiency syndrome.

We performed a computerized search on sulfadiazine-associated nephrotoxicity reported in human immunodefiency virus (HIV)-infected patients in the international literature. Including an original case report, we summarized 35 acquired immunodefiency syndrome (AIDS) patients from 1987 to 1995 in an analysis comparing their features to historical HIV-negative controls from the 1940s and 1950s. Likely due to a high prevalence of potential risk factors, incidence of sulfadiazine-associated renal impairment was 1.9%-7.5% in AIDS patients and 1%-4% in HIV-negative controls. Its occurrence appeared to be delayed in HIV-infected patients with a median of about 3 weeks of medication compared with about 10 days in HIV-negative subjects. Correspondingly, the cumulative sulfadiazine dose at manifestation doubled in AIDS patients with a median of 84 g versus 40 g in controls. Patients usually presented with flank or lumbar pain, oliguria, and (macro) hematuria. Urinalysis showed typical "sheaves of wheat" crystalluria, erythrozyturia, and, less commonly, leukozyturia and proteinuria. Echogenic (mostly peripelvic) densities, renal stones, and hydronephrosis are frequent findings on ultrasound examination, whereas X-ray examination possesses a low diagnostic sensitivity. The principle aim of therapy in these patients is to (re)institute the physicochemical urinary solubility of sulfadiazine and its metabolites. For this purpose, forced rehydration and, most importantly, urine alkalinization proved to be effective measures without an absolute need to withhold the drug. Provided prophylactic and therapeutic recommendations are complied with, outcome of this drug-related side effect is usually excellent, and rare relapses will similarly respond well.

AIDS-Related Opportunistic Infections↗
PubMed1996

Visceral leishmaniasis emerging as an important opportunistic infection in HIV-infected persons living in areas nonendemic for Leishmania donovani.

BACKGROUND: Visceral leishmaniasis is an important infection in patients infected with human immunodeficiency virus and living in areas endemic for Leishmania sp. Leishmaniasis, however, is rarely suspected in patients residing in nonendemic countries. METHODS: Retrospective case analysis of 15 patients with human immunodeficiency virus infection and leishmaniasis treated at seven German clinics. The clinicopathological features and the diagnostic role of biopsy and/or cytology as compared to serology were evaluated. RESULTS: All patients were severely immunocompromised. One patient was first diagnosed at autopsy. One patient with mucocutaneous disease was diagnosed by nasal biopsy. All others had amastigotes detected in bone marrow (13/13), liver (3/3), and gastrointestinal mucosa (4/4). Serology was positive in only 6 or 13. CONCLUSION: Visceral leishmaniasis is an important opportunistic infection in patients with acquired immunodeficiency syndrome and it must be ruled out in every patient with fever and/or pancytopenia and an appropriate travel history. Because serological diagnosis is often insufficient, pathologists must be aware of the association between human immunodeficiency virus infection and leishmaniasis. Diagnosis depends on detection of the parasite in submitted specimens.

AIDS-Related Opportunistic Infections↗
PubMed1995

Efficacy, safety, and tolerance of low-dose, long-term interferon-alpha 2b and zidovudine in early-stage AIDS-associated Kaposi's sarcoma.

Seventeen male homosexual outpatients with limited but progressive AIDS-associated Kaposi's sarcoma (KS) of skin, lymph nodes, oral cavity, and gastrointestinum were consecutively enrolled in an open, nonrandomized, prospective study. Patients received low-dose IFN-alpha 2b (3 MIU t.i.w.) in combination with 250 mg ZDV b.i.d. After remission of KS, continuation of treatment as maintenance therapy was provided. Eleven (65%) of 17 patients had a complete (CR) or partial remission (PR) of KS lasting more than 24 months in four patients. Response to treatment was strongly dependent on pretreatment values of CD4+ lymphocyte counts, CR and PR occurred only in patients with pretreatment levels higher than 250 CD4+ lymphocytes per microliter. Treatment was generally well tolerated and without severe hematologic side effects attributable to the addition of IFN-alpha 2b to ZDV treatment. This study suggests that a combination of low-dose IFN-alpha 2b and ZDV is therapeutically effective and well tolerated in early stages of progressive KS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Serum levels of stem cell factor are increased in asymptomatic human immunodeficiency virus-infected patients and are associated with prolonged survival.

Cytopenia is a common complication of human immunodeficiency virus (HIV) infection and can affect different hematopoietic lineages, including erythropoiesis, lymphopoiesis, thrombopoiesis, and granulopoiesis. Stem cell factor (SCF), a cytokine expressed by bone marrow stromal cells, is a multipotential growth factor acting on early progenitor cells of most hematopoietic lineages. Therefore, we investigated the serum SCF levels in 74 HIV-infected persons without active secondary infection at different stages of HIV infection [Centers for Disease Control (CDC) stages A through C]. Circulating SCF levels were determined by enzyme-linked immunosorbent assay and were found to be significantly elevated in CDC stage A as compared with normal controls (7.18 +/- 1.94 ng/mL v 3.95 +/- 0.91 ng/mL, P = .04). However, in CDC groups B and C, SCF levels were lower than in CDC group A (3.29 +/- 0.75, P = .162, and 1.95 +/- 0.39, P = .005, respectively). Serum levels greater than 1.8 ng/mL were associated with a longer survival (P = .0037) in 74 HIV type 1 (HIV-1)-seropositive patients monitored for up to 114 weeks, suggesting that this cytokine may be directly associated with the disease course. A Cox proportional hazards model showed SCF to be an independent prognostic factor for survival (risk ratio for death, 0.73; 95% confidence interval, 0.56 to 0.95; P = .019). Serum SCF levels decreased on follow up in 24 of 38 patients or remained below 0.4 ng/mL in 10 of 38 patients from whom a second blood sample was collected after a mean interval of 44 weeks. To determine potential regulatory factors of SCF expression by stromal cells, we exposed cultured fibroblasts to various cytokines. Only interleukin-4 (IL-4) upregulated SCF mRNA. As IL-4 is modulated during early HIV disease, it may be a key regulator of SCF secretion. Further studies are required to elucidate the mechanism of SCF action and regulation in patients with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Treatment of toxoplasmosis retinochoroiditis with atovaquone in an AIDS patient].

BACKGROUND: Treatment of ocular toxoplasmosis in HIV-infected patients with standard drug regimens (Pyrimethamine, Clindamycine, Sulfonamides) is very often complicated by side-effects and adverse reactions. On the other hand, maintenance therapy must be continued life long, because of the high recurrence rates. Atovaquone (Hydroxynaphthoquinon) is tolerated excellently and is very effective against tachyzoits of toxoplasma gondii and its cysts. PATIENT HISTORY AND CLINICAL FINDINGS: A 49-year-old homosexual man with AIDS developed an allergic rash after being treated with a course of Pyrimethamine and Clindamycine for unilateral, bifocal ocular toxoplasmosis for 13 days. Therapy with Atovaquone 3 x 750 mg/d was instituted and within 8 days the infiltrates healed leaving retinochorioidal scars. THERAPY AND CLINICAL COURSE: During maintenance therapy with Atovaquone (3 x 750 mg/d) two relapses occurred, the first after 2 months and the second after 8 months. The recurrences were successfully treated by increasing the dosage of Atovaquone to 4 x 750 mg/d and the addition of Trimethoprime/Sulfamethoxazol and Clindamycine/Pyrimethamine respectively. Reexposition was tolerated without an allergic reaction. Under maintenance therapy with Pyrimethamine the patient was free of recurrences for another 4 months until he died. CONCLUSIONS: Atovaquone is an effective and well tolerated substance for the treatment of ocular toxoplasmosis. In contrast to earlier reports, two recurrences occurred under maintenance therapy. It cannot be excluded that the patient was incomplient and did not take the tablets according to our prescription. Future clinical investigations have to control the efficacy of Atovaquone in the therapy of ocular toxoplasmosis.

AIDS-Related Opportunistic Infections↗