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R Haas

Publications and source records attributed to R Haas.

At least 109 records · Page 6Linked to original sources
PubMed1999

A theoretical approach to select effective antisense oligodeoxyribonucleotides at high statistical probability.

Up to now, out of approximately 20 antisense oligodeoxyribonucleotides (as ODN) selected and tested against a given target gene, only one species shows substantial suppression of target gene expression. In part, this seems to be related to the general assumption that the structures of local target sequences or antisense nucleic acids are unfavorable for efficient annealing. Experimental approaches to find effective as ODN are extremely expensive when including a large number of antisense species and when considering their moderate success. Here, we make use of a systematic alignment of computer-predicted secondary structures of local sequence stretches of the target RNA and of semi-empirical rules to identify favorable local target sequences and, hence, to design more effective as ODN. The intercellular adhesion molecule 1 (ICAM-1) gene was chosen as a target because it had been shown earlier to be sensitive to antisense-mediated gene suppression. By applying the protocol described here, 10 ICAM-1-directed as ODN species were found that showed substantially improved inhibition of target gene expression in the endothelial cell line ECV304 when compared with the most effective published as ODN. Further, 17 out of 34 antisense species (50%) selected on the theoretical basis described here showed significant (>50%) inhibition of ICAM-1 expression in mammalian cells.

Cell Line, Transformed↗
PubMed1999

Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the cag pathogenicity island.

Helicobacter pylori interacts with the apical membrane of the gastric epithelium and induces a number of proinflammatory cytokines/chemokines. The subsequent infiltration of macrophages and granulocytes into the mucosa leads to gastric inflammation accompanied by epithelial degeneration. Gastric diseases, e.g. peptic ulcer or gastric adenocarcinoma, are more common among people infected with H. pylori strains producing VacA (vacuolating cytotoxin A) and possessing a cag (cytotoxin-associated antigen A) pathogenicity island. For the induction of the cytokine/chemokine genes in response to H. pylori, we studied the signaling leading to the nuclear activation of the early response transcription factor activator protein 1 (AP-1). We found that H. pylori strains carrying the pathogenicity island induce activation of AP-1 and nuclear factor kappaB. In contrast to the wild type or an isogenic strain without the vacA gene, isogenic H. pylori strains with mutations in certain cag genes revealed only weak AP-1 and nuclear factor kappaB activation. In respect to the molecular components that direct AP-1 activity, our results indicate a cascade of the cellular stress response kinases c-Jun N-terminal kinase, MAP kinase kinase 4, and p21-activated kinase, and small Rho-GTPases including Rac1 and Cdc42, which contributes to the activation of proinflammatory cytokines/chemokines induced by H. pylori encoding the cag pathogenicity island.

Antigens, Bacterial↗
PubMed1999

Peutz-Jeghers syndrome: four novel inactivating germline mutations in the STK11 gene. Mutations in brief no. 227. Online.

The diagnosis of Peutz-Jeghers syndrome is based on the occurrence of hamartomatous gastrointestinal polyps and perioral pigment spots. In view of the development of hamartomatous polyps in several syndromes and the variability of pigment spots in Peutz-Jeghers patients, identification of affected individuals is difficult. Recently, germline mutations in the STK11 gene have been reported as a molecular cause of Peutz-Jeghers syndrome. We present four novel inactivating mutations identified by direct sequencing of all 9 exons of the STK11 gene in 4 patients suggestive of Peutz-Jeghers syndrome: three frameshift mutations (125-137del; 474-480del; 516-517insT) and one nonsense mutation (Q220X). Our data obtained in these patients and in those reported previously emphasize the diagnostic value of histological discrimination between different types of hamartomatous polyps and of molecular analysis, particularly in cases with no family history of the disease.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online.

In order to obtain novel mutations in the recently discovered Wilson disease gene, we screened 5 unrelated German individuals for mutations in the 21 exons and their flanking intronic sequences. We detected 9 mutations affecting the Wilson disease gene. Four of those, designated 802-808delTGTAAGT, 2008-2013delTATATG, Cys985Thr, and Ile1148Thr have not yet been reported. One patient had a homozygous mutation whereas the remaining four subjects were compound heterozygous. Therefore these data confirm, that mutations causing Wilson disease are frequently found in affected subjects and they are very heterogenous.

Adenosine Triphosphatases↗
PubMed1999

Second malignancies after Hodgkin's disease: the Munich experience.

The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic relation to the field of previous radiotherapy. Taken together, in our patient population, we observed all three categories of SM (solid tumors, leukemias, NHL). The risk for second leukemias is lower than in previous studies, whereas the risk of second NHL is somewhat higher. We confirm that splenectomy is a possible risk factor for SM. Even after correction for the age-specific cancer incidence, treatment intensity is associated with the development of second malignant tumors. Continued follow-up is mandatory after treatment for HD. Since the prognosis of most SM is unfavorable, early recognition and prevention are of the utmost importance.

Adolescent↗
PubMed1999

Adjuvant high-dose therapy with peripheral blood stem cell support for patients with high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 107 patients with high-risk stage II/III breast cancer. There were 90 patients with more than 9 tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7,500 mg/m(2)) and epirubicin (120 mg/m(2)) was given, and PBSC were harvested during granulocyte colony-stimulating factor (G-CSF)-supported leukocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose 12,000 mg/m(2)), carboplatin (900 mg/m(2)) and epirubicin (180 mg/m(2)). Patients were autografted with a median number of 4.1 x 10(6) CD34+ cells/kg (range 1.9-26.5 x 10(6)), resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-nine patients (27.1% of all patients) relapsed between 3 and 46 months following the last cycle of high-dose therapy (median 15 months). The probability of disease-free and overall survival at 3 years was 56% and 83%, respectively. A multivariate analysis showed that patients with stage II disease had a significantly better probability of disease-free survival (71%) in comparison with patients with stage III disease (30%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (62%) compared with patients with receptor-negative ones (40%). In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy including the addition of non-cross-resistant drugs or immunological approaches may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗
PubMed1999

A plasmid-based vector system for the cloning and expression of Helicobacter pylori genes encoding outer membrane proteins.

Helicobacter pylori produces a number of proteins associated with the outer membrane, including adhesins and the vacuolating cytotoxin. We observed that the functional expression of such proteins is deleterious to Escherichia coli, the host bacterium used for gene cloning. Therefore, a general method was developed for the functional expression of such genes on a shuttle vector in H. pylori, which has been termed SOMPES (Shuttle vector-based Outer Membrane Protein Expression System). The intact, active gene is reconstituted by recombination in H. pylori from partial gene sequences cloned on an E. coli-H. pylori shuttle vector. This system was established in an H. pylori strain carrying a precise, unmarked chromosomal deletion of the vacA gene, which was constructed by adapting the streptomycin sensitivity system to H. pylori. It is based on the expression of the H. pylori rpsL gene as a counterselectable marker in the genetic background of an rpsL mutant. The utility of this approach is demonstrated by the expression of a recombinant gene encoding vacuolating cytotoxin (vacA) and a recombinant gene encoding an adherence-associated outer membrane protein (alpA) in H. pylori.

Bacterial Outer Membrane Proteins↗
PubMed1999

Ceftazidime in combination with glycopeptide antibiotic is an effective first-line therapy for patients undergoing high-dose therapy with autologous peripheral blood stem cell support.

It was the objective of this study to evaluate the efficacy and toxicity of an empirical antibiotic therapy consisting in ceftazidime and a glycopeptide antibiotic. All patients enrolled in the study had hematological malignancies and underwent high-dose therapy with peripheral blood stem cell (PBSC) support. In this retrospective study, 183 of 207 patients who had received a PBSC-supported high-dose therapy were evaluable. Any patients who had fever higher than 38.5 degrees C received ceftazidime in combination with vancomycin (105 patients) or teicoplanin (69 patients). In 80 of 174 patients with fever (45%) the fever resolved within 72 h as a result of the treatment with ceftazidime and the glycopeptide antibiotic. In nonresponding patients, the changes included the replacement of ceftazidime by imipenem/cilastin (94 patients) and the addition of erythromycin (12 patients) or metronidazole (3 patients). Amphotericin B was administered in 29 patients. Following hematological reconstitution, the fever and clinical signs, including radiographic findings, resolved in 20 primarily nonresponding patients. In blood cultures, a significantly higher incidence of gram-positive than of gram-negative bacteria was observed (26 vs 7). The toxicity of the first-line antibiotic therapy was limited to allergic skin reactions in 12 patients. Ceftazidime in combination with a glycopeptide antibiotic provides an effective and safe first-line therapy for patients with neutropenic fever following PBSC-supported high-dose therapy.

Adolescent↗
PubMed1999

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗
PubMed1999

Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content.

The efficacy of an immunomagnetic purging method and the Isolex 300 devices were assessed for selecting CD34+ cells from leukapheresis products of 29 patients with non-Hodgkin's lymphoma (NHL), 39 with multiple myeloma and 34 with breast cancer. The mean purity of the CD34+ cell population was 93.6% and the mean recovery was 67.7%. Following enzymatic cleavage by chymopapain the expression of Thy-1 and Leu-8 was significantly reduced without affecting haematological recovery. The population of selected CD34+ cells of 4/8 patients with follicular lymphoma became PCR-negative. A 2.5 log reduction of tumour cells could be achieved in four patients with multiple myeloma as shown by a quantitative PCR assay. There were no tumour cells detectable in any of the 19 CD34+ cell preparations of patients with breast cancer. In 64 patients who received 94 cycles of high-dose therapy, a mean number of 4.7x 10(6) CD34+ cells/kg were autografted. The time needed for platelet reconstitution was different when a comparison was made with 156 patients, who had received unmanipulated leukapheresis products (10 v 12 d, P = 0.006). No significant differences with regard to neutrophil recovery were noted. Five patients had a graft failure. Two of them died (on day 78 and 88 following PBSCT), and three patients were rescued with unmanipulated back-up transplants. In conclusion, the immunomagnetic selection of CD34+ cells provides autografts with reduced tumour cell content and an engraftment ability similar to that of unmanipulated autografts.

Antigens, CD34↗
PubMed1999

Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients.

Peripheral blood progenitor cells (PBPC) can be mobilized using chemotherapy and granulocyte colony-stimulating factor (G-CSF). We and others previously reported a correlation of steady-state PBPC counts and the PBPC yield during mobilization in a small group of patients. Here we present data on 100 patients (patients: 25 non-Hodgkin's lymphoma (NHL), five Hodgkin's disease, 35 multiple myeloma (MM), 35 solid tumour) which enabled a detailed analysis of determinants of steady-state PBPC levels and of mobilization efficiency in patient subgroups. Previous irradiation (P = 0.0034) or previous chemotherapy in patients with haematological malignancies (P = 0.0062) led to a depletion of steady-state PB CD34+ cells. A correlation analysis showed steady-state PB CD34+ cells (all patients: r = 0.52, P < 0.0001; NHL patients, r = 0.69, P = 0.0003; MM patients: r = 0.66, P = 0.0001) and PB colony-forming cells can reliably assess the CD34+ cell yield in mobilized PB. In patients with solid tumour a similar trend was observed in mobilization after the first chemotherapy cycle (r = 0.51, P = 0.05) but not if mobilization occurred after the second or further cycle of a sequential dose-intensified G-CSF-supported chemotherapy regimen, when premobilization CD34+ counts were 18-fold elevated (P = 0.004). When the patients with MM (r = 0.63, P = 0.0008) or with NHL (r = 0.65, P = 0.006) were analysed separately, a highly significant correlation of the steady-state PB CD34+ cell count to the mean leukapheresis CD34+ cell yield was found, whereas no correlation was observed for patients with a solid tumour. For patients with haematological malignancies estimates could be calculated which, at a specific steady-state PB CD34+ cell count, could predict with a 95% probability a defined minimum progenitor cell yield. These results enable recognition of patients who mobilize PBPC poorly and may assist selection of patients for novel mobilization regimens.

Adult↗
PubMed1999

Experimental study of the damping behaviour of IMZ implants.

Measurements of the damping behaviour of dental implants with the Periotest device are considered to be an objective means to assess the mobility of implants. The effects of the position of an implant in the maxilla or mandible, the period of time passing between the measurements and implant placement and the height at which the Periotest measurements are performed on the damping behaviour of implants have been discussed controversially. This experimental study examined the influence of the use of different measuring devices, the measuring height and the embedding depth on the damping behaviour of IMZ implants. The implants were embedded in resin at different depths and damping measurements were carried out at different measuring heights. It was found that the values rose with an increasing measuring height and a decreasing embedding depth. Analysis of variance was used to assess the influence of the embedding depth and revealed that the embedding depth had a significant impact on the measuring values at each measuring height, above 6 mm. Moreover, it was found that the higher the measuring height, the higher the measured values and the greater the differences between the values obtained at the individual depths. The different measuring devices had no influence on the measuring results (P = 0.79). The results of this study suggest that a longitudinal follow-up of the peri-implant residual bone height around individual implants is possible. Single measuring values by themselves do not allow any conclusions about the prognosis of an implant. The assessment of the peri-implant bone height through Periotest measurements is conceivable only when a table of damping values taking into account the physical length of the implant, the embedding depth and the measuring height for the examined implant system is available. In cylindrical implants, the head of the available prefabricated measuring post can be recommended as a constant measuring point for further studies, especially when the results are to be compared with those obtained by other study groups.

Acceleration↗
PubMed1999

Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue.

In this study, we isolated and characterized a chromosomal locus of Helicobacter pylori previously identified by transposon shuttle mutagenesis as being involved in the adhesion of the pathogen to gastric epithelial cells. Two closely homologous genes were identified, designated as alpA and alpB, encoding outer membrane (OM) proteins of 518 amino acids each. They are members of the outer membrane protein supergene family identified in the H. pylori 26695 complete genome sequence. AlpA carries a functional lipoprotein signal sequence. AlpB carries a putative standard N-terminal signal sequence and shows a strong amino-acid sequence identity to AlpA. Transposon insertion mutagenesis, immunoblotting and primer extension studies indicate that both genes are organized in an operon, but no obvious consensus promoter sequence was found upstream of the transcriptional start site. The C-terminal portion of both proteins is predicted to form a porin-like beta-barrel in the outer membrane, consisting of 14 transmembrane amphipathic beta-strands. Adhesion experiments with defined isogenic mutants indicate that both proteins are necessary for specific adherence of H. pylori to human gastric tissue. The pattern of AlpAB-dependent adherence of H. pylori to the gastric epithelial surface shows a clear difference to the BabA2-mediated adherence to Lewis, suggesting that a different receptor is involved.

Algorithms↗
PubMed1999

Helicobacter pylori cadA encodes an essential Cd(II)-Zn(II)-Co(II) resistance factor influencing urease activity.

Inactivation of Helicobacter pylori cadA, encoding a putative transition metal ATPase, was only possible in one of four natural competent H. pylori strains, designated 69A. All tested cadA mutants showed increased growth sensitivity to Cd(II) and Zn(II). In addition, some of them showed both reduced 63Ni accumulation during growth and no or impaired urease activity, which was not due to lack of urease enzyme subunits. Gene complementation experiments with plasmid (pY178)-derived H. pylori cadA failed to correct the deficiencies, whereas resistance to Cd(II) and Zn(II) was restored. Moreover, pY178 conferred increased Co(II) resistance to both the cadA mutants and the wild-type strain 69A. Heterologous expression of H. pylori cadA in an Escherichia coli zntA mutant resulted in an elevated resistance to Cd(II) and Zn(II). Expression of cadA in E. coli SE5000 harbouring H. pylori nixA, which encodes a divalent cation importer along with the H. pylori urease gene cluster, led to about a threefold increase in urease activity compared with E. coli control cells lacking the H. pylori cadA gene. These results suggest that H. pylori CadA is an essential resistance pump with ion specificity towards Cd(II), Zn(II) and Co(II). They also point to a possible role of H. pylori CadA in high-level activity of H. pylori urease, an enzyme sensitive to a variety of metal ions.

Adenosine Triphosphatases↗
PubMed1999

Comparison of different lymphoma cell purging modalities: An experimental study with K422 lymphoma cells.

Blood-derived autografts from patients with non-Hodgkin's lymphoma (NHL) are frequently contaminated with clonogenic lymphoma cells. In order to obtain a more efficient lymphoma cell depletion from the transplants we compared the efficiency of different purging techniques: B-cell-directed depletion, CD34+ selection by immunomagnetic beads (IMB selection) or by immunoadsorption with a biotin-avidin column (BAC selection). Furthermore, two combination approaches were investigated: IMB selection after B-cell depletion as well as BAC selection after B-cell depletion. To assess purging efficiency, fluorescence-tagged (PKH26) K422 follicular NHL cells were admixed to the respective samples of leukapheresis products. BAC selection following B-cell depletion compared to BAC selection alone showed no significant differences in CD34+ purity (77 +/- 12. 5% vs. 70.7 +/- 5.4%) (mean +/- SE) or CD34+ recovery (35.3 +/- 8.5% vs. 32.8 +/- 10.4%), but a significantly (p < 0.005) higher lymphoma cell purging efficiency (log 4.32 +/- 0.15 vs. log 2.92 +/- 0.19). IMB selection following B-cell depletion and IMB selection alone resulted in a CD34+ purity of 40.8 +/- 8.7% and 64.7 +/- 7.9%, a CD34+ recovery of 47.2 +/- 8.3% and 26.5 +/- 6.5% and a lymphoma cell purging efficiency of log 3.68 +/- 0.16 and log 3.48 +/- 0.21, respectively. Lymphoma cell purging efficiency after either CD34 selection method alone as well as after either double purging method was significantly higher (p < 0.0005 and p < 0.00005, respectively) compared to B-cell depletion alone (log 1.44 +/- 0.23). Our results argue for the combination of different purging modalities to achieve a maximal lymphoma cell depletion.

Antigens, CD34↗
PubMed1999

[PCR determination of an association between class II HLA and pemphigus vulgaris].

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membranes. It is characterized by the presence of an autoantibody directed against desmoglein 3, which causes acantholysis and blister formation. In this study, we examined the HLA antigens of 30 caucasian argentinian patients compared with 199 controls. We used the PCR-SSO method (Polymerase Chain Reaction-Sequence Specific Oligonucleotide). We found that PV patients had significantly increased frequencies of HLA DR4 (RR = 3.80, P = 0.001) and HLA DR 14 (RR = 5.97, P = 0.0001). As in other populations, two associated alleles were found: the first was DR beta 1*0402 (RR = 44.70, P = 10.7) and DQ beta 1*0302 (RR = 71.82, P = 10(-7)) and the second was DR beta 1*1401 (RR = 117.94, P = 10(-7)) y DQ beta 1*0503 (RR = 86.95, P = 10(-7)).

Alleles↗
PubMed1999

Lipid evaluation in HIV-1-positive patients treated with protease inhibitors.

There is accumulating evidence that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) can induce hyperlipidaemia. To evaluate the frequency and type of hyperlipidaemia in PI-treated patients, 98 outpatients were prospectively analysed for their lipoprotein characteristics at the Medizinische Hochschule in Hannover, Germany. Fifty-seven percent of the patients studied presented with hyperlipidaemia. Both hypertrigylceridaemia (type IV and V hyperlipoproteinaemia, 33%) and hypercholesterolaemia (type IIa hyperlipoproteinaemia, 6%) were detectable. The remaining 18% had a type IIb hyperlipoproteinaemia. Increased lipid levels were highly statistically significant compared to a control group of PI-naive HIV-1-infected patients [low-density lipoprotein (LDL) 146 mg/dl (range, 53-274 mg/dl) versus 105 mg/dl (range, 22-188 mg/dl; P=0.0006); very-low-density lipoprotein (VLDL) 35.5 mg/dl (5-253 mg/dl) versus 18 mg/dl (range, 3-94 mg/dl; P=0.0002)]. All PIs used (saquinavir, indinavir, nelfinavir and ritonavir) were associated with this variable form of hyperlipidaemia according to the Fredrickson classification. There was no significant correlation of any determined lipid value with the duration of treatment. A higher frequency of the apolipoprotein E2 allele and E4 allele was observed in the hyperlipidaemic subjects. Patients with excessive hypertriglyceridaemia showed a reduced lipoprotein lipase activity. Lipodystrophy was observed especially in hyperlipidaemic patients and to a lesser extent in normolipidaemic subjects. The frequency of hyperlipidaemic risk factors was surprisingly high in the group studied, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 PI-treated patients. Therefore, PI-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions.

Acquired Immunodeficiency Syndrome↗