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Biomedical subjects

F Kramer

Publications and source records attributed to F Kramer.

At least 19 recordsLinked to original sources
PubMed2003

Oleate, not ligands of the receptor for advanced glycation end-products, promotes proliferation of human arterial smooth muscle cells.

AIMS/HYPOTHESIS: Diabetes accelerates cardiovascular disease caused by atherosclerosis. Accordingly, diabetes accelerates atherosclerotic lesion progression and increases arterial smooth muscle cell proliferation. We hypothesized that diabetes can exert growth-promoting effects on smooth muscle cells via increased advanced glycation end-products or by dyslipidaemia. METHODS: Primary human arterial smooth muscle cells were stimulated with advanced glycation end-products, other ligands of the receptor for advanced glycation end-products or fatty acids common in triglycerides. Cell proliferation was measured as DNA synthesis, cell cycle distribution and cell number. Effects of oleate on cellular phospholipids, diacylglycerol, triglycerides and cholesterol esters were analyzed by thin-layer chromatography, and oleate accumulation into diacylglycerol was confirmed by gas chromatography. RESULTS: Human arterial smooth muscle cells express the receptor for advanced glycation end-products, but its ligands N(epsilon)-(carboxymethyl)lysine-modified proteins, methylglyoxal-modified proteins, S100B polypeptide and amyloid-beta (1-40) peptide, exert no mitogenic action. Instead, oleate, one of the most common fatty acids in triglycerides, enhances platelet-derived growth factor-BB-mediated proliferation and oleate-containing 1,2-diacylglycerol formation in smooth muscle cells. This mitogenic effect of oleate depends on phospholipase D activity and is associated with an increased formation of oleate-enriched 1,2-diacylglycerol. CONCLUSION/INTERPRETATION: Oleate, not ligands of the receptor for advanced glycation end-products, acts as an enhancer of human smooth muscle cell proliferation. Thus, lipid abnormalities, rather than hyperglycaemia, could be a major factor promoting proliferation of smooth muscle cells in atherosclerotic lesions.

Aorta↗
PubMed1998

Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.

To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.

AIDS-Related Opportunistic Infections↗
PubMed1997

Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with the acquired immunodeficiency syndrome (AIDS). If left untreated, it may lead to progressive destruction of retinal tissue and blindness. Cidofovir is a nucleotide analogue of cytosine that has potent, prolonged in vitro and in vivo activity against herpesviruses, including many CMV isolates that are resistant to ganciclovir and foscarnet. OBJECTIVE: To determine whether intravenous cidofovir delays progression of previously untreated CMV retinitis. DESIGN: Randomized, controlled trial comparing immediate with deferred cidofovir treatment. Patients in the deferred treatment group were eligible to receive cidofovir after progression of CMV retinitis was documented by retinal photography. SETTING: Eight academic medical centers and an independent center that read retinal photographs. PATIENTS: 48 patients with AIDS and previously untreated peripheral CMV retinitis who were randomly assigned to immediate (n = 25) or deferred treatment (n = 23). INTERVENTION: Intravenous cidofovir, 5 mg/kg of body weight, once weekly for 2 weeks and then once every other week. To minimize nephrotoxicity, oral probenecid and intravenous hydration with normal saline were administered with each cidofovir infusion. MEASUREMENTS: Progression of CMV retinitis was assessed by bilateral, full-field retinal photographs that were read by an ophthalmologist who was masked to treatment assignment. Incidence of side effects, changes in visual acuity, effect on CMV shedding in urine and blood, and mortality were also assessed. RESULTS: The median time to progression of CMV retinitis was 22 days (95% CI, 10 to 27 days) in the deferred treatment group and 120 days (CI, 40 to 134 days) in the immediate treatment group (P < 0.001). Neutropenia (15%) and proteinuria (12%), both asymptomatic, were the most common serious adverse events considered to be possibly related to cidofovir. Cidofovir treatment was discontinued in 10 of 41 patients (24%) because of protocol-defined treatment-limiting nephrotoxicity. Transient reactions to probenecid, including mild to moderate constitutional symptoms or nausea, occurred in 23 of 41 patients (56%) and were dose limiting in 3 (7%). CONCLUSIONS: Cidofovir was efficacious in delaying progression of previously untreated CMV retinitis. Treatment was associated with manageable side effects; strict adherence to monitoring of renal function before cidofovir was administered and concomitant administration of probenecid and saline hydration appeared to minimize drug-related nephrotoxicity.

AIDS-Related Opportunistic Infections↗
PubMed1997

A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS.

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068.

Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.

Administration, Cutaneous↗
PubMed1995

Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis.

INTRODUCTION: The use of foscarnet and ganciclovir as a combination treatment for cytomegalovirus retinitis is increasing because of limitations associated with single agent therapy. METHODS: The pharmacokinetics of foscarnet and ganciclovir were determined in 13 patients receiving either concomitant therapy (regimen A) or daily alternating therapy (regimen B) for maintenance of cytomegalovirus disease. For regimen A, 60 mg/kg intravenous foscarnet and 3.75 mg/kg ganciclovir were sequentially administered daily; for regimen B, 120 mg/kg foscarnet and 6 mg/kg ganciclovir were administered on alternating days. For both regimens, serial blood sampling for pharmacokinetic analysis was performed for each drug alone (day 1 or 2) and after 2 weeks of combination therapy. Plasma samples for foscarnet and ganciclovir analysis were performed by means of high-performance liquid chromatography. Pharmacokinetic analysis was performed with noncompartmental methods. RESULTS: For regimen A, the plasma clearance (CL) of foscarnet did not change in the presence of ganciclovir, averaging 0.12 +/- 0.08 and 0.11 +/- 0.02 L/hr/kg on study days 2 and 14, respectively (p = 0.34). The volume of distribution (VSS) and mean residence time (MRT) also did not change significantly. CL and MRT of foscarnet did not change for regimen B, although a slight increase in VSS was observed before (0.38 +/- 0.05 L/kg) and after (0.46 +/- 0.07 L/kg) alternating therapy (p = 0.03). Ganciclovir CL did not change for either regimen, with mean values of 0.21 +/- 0.10 and 0.25 +/- 0.10 L/hr/kg (regimen A, p = 0.17) and 0.32 +/- 0.10 and 0.34 +/- 0.11 L/hr/kg (regimen B, p = 0.24). MRT and VSS were also not significantly different. CONCLUSION: These plasma data suggest that further dosage adjustments are unnecessary for or alternating maintenance therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151.

AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis who had just completed a 14-day course of ganciclovir induction therapy were randomly assigned to an alternating or concurrent combination regimen of chronic ganciclovir-foscarnet therapy for CMV retinitis. Each regimen used lower weekly cumulative doses of each drug than standard monotherapy maintenance treatment regimens. Dose-limiting toxicity attributable to foscarnet occurred in only 2 (7%) of 29 evaluatable patients, and no patients experienced dose-limiting nephrotoxicity. Although absolute neutrophil counts < 500 cells/microL occurred in 11 (38%) of 29 patients, all who subsequently used adjunctive granulocyte colony-stimulating factor had severe neutropenia prevented. Severe toxicity of any type and neutropenia, in particular, occurred significantly more frequently in patients assigned to the concurrent treatment regimen. CMV was isolated from none of 21 patients who had urine cultured and from only 1 of 24 who had blood cultured while being treated during the study (median evaluation, 12 weeks). This suggests that combination therapy provides better in vivo antiviral activity in suppressing CMV replication than previously reported with monotherapy regimens.

AIDS-Related Opportunistic Infections↗
PubMed1993

Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗
PubMed1993

Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection.

To evaluate the relationship between the clinical presentation of tuberculosis and the CD4 cell count in patients with human immunodeficiency virus (HIV) infection, we evaluated clinical and laboratory features of 97 HIV-infected patients with tuberculosis in whom CD4 cell counts were available. Extrapulmonary tuberculosis was found in 30 (70%) of 43 patients with < or = 100 CD4 cells/microL, 10 (50%) of 20 patients with 101 to 200 CD4 cells/microL, seven (44%) of 16 patients with 201 to 300 CD4 cells/microL, and five (28%) of 18 patients with > 300 CD4 cells/microL (p = 0.02). Mycobacteremia was found in 18 (49%) of 37 patients with < or = 100 CD4 cells/microL, three (20%) of 15 patients with 101 to 200 CD4 cells/microL, one (7%) of 15 patients with 201 to 300 CD4 cells/microL, and none of eight patients with > 300 CD4 cells/microL (p = 0.002). Acid-fast smears were more often positive in patients with low CD4 cell counts. Positive tuberculin skin tests were more common in patients with high CD4 counts. On chest roentgenograms, mediastinal adenopathy was noted in 20 (34%) of 58 patients with < or = 200 CD4 cells/microL and four (14%) of 29 patients with > 200 CD4 cells/microL (p = 0.04). Pleural effusions were noted in six (10%) of 58 patients with < or = 200 CD4 cells/microL and eight (28%) of 29 patients with > 200 CD4 cells/microL (p = 0.04). The CD8 cell counts did not correlate with the manifestations of tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1990

Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection.

PURPOSE: To determine the frequency with which the diagnosis of tuberculosis is delayed in patients with concomitant human immunodeficiency virus (HIV) infection, and to identify reasons for such delays. PATIENTS AND METHODS: We reviewed medical records of 52 consecutive HIV-infected patients with culture-proven tuberculosis seen at a 1,900-bed general hospital serving a predominantly indigent population in Los Angeles, where the prevalences of HIV infection and tuberculosis are high. The late-treatment (LT) group consisted of 25 patients in whom tuberculosis was untreated prior to death (n = 6) or treated more than 22 days after presentation (n = 19). The early-treatment (ET) group comprised 27 patients in whom antituberculous therapy was begun less than 16 days after presentation. RESULTS: Symptoms, physical and laboratory findings, chest roentgenographic abnormalities suggestive of tuberculosis (hilar adenopathy, pleural effusion, miliary pattern, cavitation, predominant upper lobe infiltrate), and frequencies of concomitant nontuberculous disease were similar in LT and ET groups. Delayed diagnosis of tuberculosis was attributable to errors in management in 21 (84%) of 25 LT group patients. The most common error was failure to obtain at least three sputum samples for acid-fast smear and mycobacterial culture in patients with clinical and chest roentgenographic findings compatible with tuberculosis (15 cases). Acid-fast sputum smears were positive in 25 (61%) of 41 cases of pulmonary tuberculosis. Acid-fast smears of stool were positive in eight (42%) of 19 cases. Blood cultures yielded Mycobacterium tuberculosis in 18 (38%) of 48 cases. CONCLUSIONS: Delayed therapy of tuberculosis in HIV-infected patients at our medical center was common and was not due to atypical manifestations of tuberculosis. In most cases, delays could have been avoided if adequate numbers of sputum samples for acid-fast smear and mycobacterial culture had been obtained, and if empiric antituberculous therapy had been given to symptomatic patients in whom chest roentgenographic findings were suggestive of mycobacterial disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The effect of intra-articular gadolinium-DTPA on synovial membrane and cartilage.

This investigation evaluated the potential effect of gadolinium (Gd)-DTPA-dimeglumine on synovial membrane and joint cartilage, using macroscopic, microscopic, and x-ray fluorescent spectroscopic techniques. Thirteen New Zealand white rabbits (26 knees) were used in this study, ten receiving 500 micromolar injections of Gd-DTPA-dimeglumine in their right knees; the remainder of the knees served as controls. One injected knee had minimal joint effusion and one had mild hyperemia. Microscopically four knees exhibited mild focal hyperplasia of the synovium, another three minimal focal mononuclear cell infiltration. X-ray fluorescent spectroscopy demonstrated no evidence of Gd-DTPA-dimeglumine in the synovium or articular cartilage. Neither macroscopic nor microscopic evaluation detected any Gd-DTPA-dimeglumine related effects. Gd-DTPA-dimeglumine was found to be safe for intra-articular injection in this animal model.

Animals↗
PubMed1989

Double-blind study of tenoxicam suppositories versus piroxicam suppositories in acute non-articular rheumatism.

The effectiveness and tolerability of tenoxicam and piroxicam, administered as a once-daily 20 mg suppository, were assessed in a comparative, randomised, double-blind trial in 48 subjects suffering from acute non-articular rheumatism. Both spontaneous and induced pain improved significantly with each of the treatments. There was no significant difference between the two treatments, whatever criterion of effectiveness was considered, i.e. spontaneous pain, induced pain or overall judgement. The incidence of undesirable side-effects was comparable for both treatments. Thirteen per cent of patients in the tenoxicam group and 16% of the patients in the piroxicam group experienced at least one undesirable side-effect. The majority of reported side-effects were of a digestive nature; however none of these were serious. The risk/benefit ratio of tenoxicam was found to be identical to that of piroxicam in the treatment of acute non-articular rheumatism.

Acute Disease↗
PubMed1987

Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise.

This study was undertaken to gain insight into the mechanisms responsible for the hypoferremia occurring after severe exercise. To this end, 18 athletes who were competing in a 160-km triathlon involving canoeing, cycling, and running were evaluated before the race, immediately after the finish, and thereafter at 30 min, 24 h, and 48 h. The evaluation included plasma iron, total iron-binding capacity, lactoferrin, ferritin, haptoglobin, cortisol, various enzymes, and white cell count. The cortisol, white cell count, and lactoferrin were significantly increased immediately after the race, while the plasma iron and transferrin saturation were significantly decreased. There was a 40% but nonsignificant rise in the plasma ferritin at the completion of the race, while the C-reactive protein was raised by nearly 300% at 24 h. In contrast, haptoglobin declined significantly by 24 h but was normal again 24 h later. Quantitative considerations suggested that the lactoferrin was not responsible for removing transferrin iron from circulation and hence causing the hypoferremia. Instead, it seemed more likely that the iron-related changes were occurring as part of an acute phase response initiated by muscle injury.

Acute-Phase Proteins↗
PubMed1979

[Cryosurgery in the treatment of Echinococcus alveolaris. Animal experiments].

The influence of cryosurgery on echinococcus alveolaris is studied in 100 mice. In a second series cryosurgical effects on structures of the hepatic portal (hepatic artery, portal vein, hepatic duct) were examined. The experiments showed that echinococcus alveolaris can be devitalized by cryosurgical measures at temperatures between -100 degrees C and -190 degrees C. No damage of the hepatic artery, portal vein, and hepatic duct occurred. Clinical application of cryosurgery for the treatment of inoperable echinococcus alveolaris of the hepatic portal appears to be justified.

Animals↗