Using clinical and genetic data to predict pulmonary hypertension in bronchopulmonary dysplasia.

AIM: Pulmonary hypertension significantly increases morbidity and mortality in infants with bronchopulmonary dysplasia. The frequency of single nucleotide polymorphisms in arginase-1 (ARG1 rs2781666) and dimethylarginine dimethylaminohydrolase-1 (DDAH1 rs480414) genes has been found to differ in a cohort of bronchopulmonary dysplasia patients with pulmonary hypertension (cases) and without pulmonary hypertension (controls). Therefore, we tested the hypothesis that combining these genotypes with phenotypic data would better predict pulmonary hypertension in bronchopulmonary dysplasia patients. METHODS: Bronchopulmonary dysplasia patients (n = 79) born at <35 weeks gestation were studied. Pulmonary hypertension was diagnosed by echocardiographic criteria (n = 20). ROC curves to predict pulmonary hypertension in bronchopulmonary dysplasia were generated from genotype and/or clinical data. RESULTS: Cases were born at an earlier gestation and weighed less at birth than did controls. ROC curves for rs2781666 had an AUC of 0.61, while rs480414 had an AUC of 0.66. Together, the AUC was 0.70. When clinical data were added to the genetic model, AUC was 0.73. CONCLUSION: These findings demonstrate that ROC predictive modelling of pulmonary hypertension in bronchopulmonary dysplasia improves with inclusion of both genotypic and phenotypic data. Further refinement of these types of models could facilitate the implementation of precision medicine approaches to pulmonary hypertension in bronchopulmonary dysplasia.

Arginase I gene single-nucleotide polymorphism is associated with decreased risk of pulmonary hypertension in bronchopulmonary dysplasia.

AIM: To test the hypothesis that there are single-nucleotide polymorphisms (SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD). METHODS: Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies (MAF) of cases and controls were compared using χ2 and logistic regression. RESULTS: Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD. CONCLUSION: Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates with BPD.

[Use of routine data from statutory health insurances for federal health monitoring purposes]. / Nutzungsmöglichkeiten von Routinedaten der Gesetzlichen Krankenversicherung in der Gesundheitsberichterstattung des Bundes.

Federal health monitoring deals with the state of health and the health-related behavior of populations and is used to inform politics. To date, the routine data from statutory health insurances (SHI) have rarely been used for federal health monitoring purposes. SHI routine data enable analyses of disease frequency, risk factors, the course of the disease, the utilization of medical services, and mortality rates. The advantages offered by SHI routine data regarding federal health monitoring are the intersectoral perspective and the nearly complete absence of recall and selection bias in the respective population. Further, the large sample sizes and the continuous collection of the data allow reliable descriptions of the state of health of the insurants, even in cases of multiple stratification. These advantages have to be weighed against disadvantages linked to the claims nature of the data and the high administrative hurdles when requesting the use of SHI routine data. Particularly in view of the improved availability of data from all SHI insurants for research institutions in the context of the "health-care structure law", SHI routine data are an interesting data source for federal health monitoring purposes.

Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands.

Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.

Whole body vibration added to endurance training in obese women - a pilot study.

Whole body vibration (WBV) training is an increasingly popular training method that is strongly promoted for weight loss, but scientific data on its effectiveness, particularly in obese subjects, are sparse. 14 obese women (BMI: 37.4 ± 1.3 kg/m2) randomized to 2 different groups (each n=7) participated in a 6-week endurance training program that was either combined or not combined with additional WBV training. Anthropometric measures, phase angle and body composition (assessed by bioelectrical impedance analysis; BIA), and resting energy expenditure (REE) were obtained before and after the training program. Body weight did not change during the training period (P=0.87), but waist circumference decreased in both groups (P=0.007; WBV: -3.4 ± 1.4 cm; no-WBV: -1.7 ± 0.7 cm) independent of WBV training (P=0.29 for group×time interaction). BIA revealed an enhancing effect of WBV training in comparison to no-WBV training on the phase angle (+0.20 ± 0.12° vs. -0.19 ± 0.12°; P=0.04) and calculated body cell mass (+0.8 ± 0.2 vs. -0.3 ± 0.4 kg; P=0.02), while calculated percentage fat mass decreased in both conditions (P=0.05) to similar extent (P=0.59; WBV: -0.8 ± 0.2%; no-WBV: -0.4 ± 0.5%). REE increased across the training (P=0.01; WBV: +77 ± 33 kcal/24 h; no-WBV: +68 ± 34 kcal/24 h), with this increase again not depending on WBV condition (P=0.85). Results of our pilot study in obese women provide preliminary evidence for a beneficial effect of WBV, when added to endurance training, on the bioelectrical phase angle, an increasingly recognized marker of individual's health status.

Post-infectious irritable bowel syndrome--a review of the literature.

INTRODUCTION: Despite considerable research efforts, the epidemiological characteristics of post-infectious symptoms of the irritable bowel syndrome-type (PI-IBS) are not yet well defined. Estimates of its incidence after gastrointestinal (GI) infection show considerable variation and the number of patients with a history of a GI infection among all patients with IBS is practically unknown. This review aims at summarizing published estimates (i) on the prevalence of PI-IBS among all IBS patients and (ii) on PI-IBS incidence after GI infection, critically discusses methodological differences that may explain the variation of the presented findings and gives an overview on currently identified risk factors for the development of PI-IBS. METHODS: A systematic literature review was perfomed of studies indexed in PUBMED that assessed the epidemiology and risk factors of PI-IBS. RESULTS: The reported incidence of PI-IBS ranges for epidemic infections between 7 and 36 %, for individual infections between 4 and 36 % and for traveller's diarrhea from 4 to 14 %. Estimates of the prevalence of PI-IBS range from as low as 7 % to more than ⅓ of all IBS patients, depending on the study design. The predictors and biomarkers are varying among the studies. CONCLUSION: PI-IBS appears to be common following infectious enteritis and among all IBS patients, but precise estimates are still lacking.

Cadmium, copper, iron, and zinc concentrations in kidneys of grey wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada).

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

Single nucleotide polymorphisms in the dual specificity phosphatase genes and risk of necrotizing enterocolitis in premature infant.

BACKGROUND: Differences in the susceptibility of preterm infants to develop necrotizing enterocolitis (NEC) implicate potential genetic differences in response to the inflammatory stimuli leading to NEC. Dual specificity phosphatases (DUSPs) are a key suppressor pathway of the mitogen-activated protein kinase (MAPK) pro-inflammatory signaling pathway. We hypothesized that inherited single nucleotide polymorphisms (SNPs) in DUSP genes contribute to NEC susceptibility in premature infants. METHODS: Patients admitted between 2010 and 2015 born at <  32 weeks GA and≤1,500 g BW with stage II+NEC (cases; n = 50) and age, weight-matched controls (n = 38) were included. Blood samples were collected for DNA isolation. Agena Mass Array assay was used to examine 31 SNPs in 9 different DUSP genes. Calculated minor allele frequencies (MAF) for cases and controls were compared using χ2 and logistic regression. RESULTS: The presence of the rs704074 SNP was associated with a 48% decreased risk of developing NEC (OR 0.52; 95% CI 0.27- 1.01, p = 0.04). The odds of surgical NEC decreased by 78% (OR 0.22; 95% CI 0.06- 0.84, p = 0.027) for each copy of rs704074/G allele in patients with NEC. CONCLUSION: In this small single-center pilot study, DUSP-6 SNP (rs704074) was associated with a lower risk of developing NEC and surgical NEC, the most severe form of NEC, in preterm infants.

Single-nucleotide polymorphism in the SCCmec-orfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains.

A number of real-time PCR assays for direct detection of methicillinresistant (MRSA) in clinical specimens are targeting staphylococcal cassette chromosome mec (SCCmec) right extremity sequences and the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. When testing 184 MRSA strains of human and animal origin from geographically distinct locations, we identified several characteristic single-nucleotide polymorphisms (SNPs) within the SCCmec-orfX junction of livestock-associated (LA) MRSA CC398 which serve as suitable strain markers for screening purposes. Within an assay time of 60 minutes and an additional 10 minutes for the melting curve analysis, all MRSA CC398 isolates were correctly identified by their characteristic T(m) value in the commercial LightCycler MRSA Advanced test. Studies to confirm the diagnostic accuracy of the SNP-based strain identification assay with a larger collection of clinical and LA-MRSA strains are ongoing.

The effects of ageing on the colonic bacterial microflora in adults.

BACKGROUND: The composition of the fecal mircoflora and its changes on ageing have rarely been investigated in large samples of both patients and volunteers. METHODS: We analysed the fecal flora by conventional microbiological testing (Kyberstatus, Institute of Microecology, Herborn, Germany) of stool samples from 35 292 adults (age: 46.3 +/- 0.08 [18 to 96] years, 9564 males, 24 784 females; remaining = missing data) with different intestinal and non-intestinal diagnoses for total colony-forming units (CFU) (per g stool) as well as relative abundance of Bifidobacteria, Bacteroides spp., Escherichia coli, Enterococcus spp., and Lactobacillus spp. with respect to age, gender, and clinical data available (e. g., stool consistency and pH). RESULTS: The total CFU was stable and showed no age- or gender-related changes. Individual bacterial species constantly and significantly increased with age (E. coli, Enterococci spp.), or decreased at higher age (Bacteroides spp.), or were stable throughout the life span (Lactobacilli, Bifidobacteria). Gastrointestinal diagnoses (Crohn's disease, n = 198; ulcerative colitis, n = 515; irritable bowel syndrome, n = 7765; other GI diagnoses, n = 10 478) tended to exhibit some specificity of the bacterial profile, and when GI diagnoses were excluded, the age-related bacterial profile of the remaining group (n = 15 619, m:f = 4197:11 422) was not different. CONCLUSION: Conventional microbiological investigations of the fecal microbiota showed both bacteria-specific as well as a general pattern of ageing of the colonic microbiota, with the last decades (more than 60 years) demonstrating the most profound changes. It remains to be shown whether these changes reflect direct changes of the gut microbiota, the mucosal innate immunity, or indirect consequences of age-related altered nutrition.

[Questionnaire for the utilization of the Emergency Department : Implications for the patient survey]. / Fragebogen zur Inanspruchnahme der Notaufnahmen : Implikationen für die Patientenbefragung.

BACKGROUND: For several years, Emergency Departments (ED) in Germany have observed increasing patient numbers, resulting in ED crowding. This leads to the question of whether patients with nonurgent conditions could also receive adequate treatment in primary care. Our objective was to develop a quantitative questionnaire to investigate in a larger patient group the reasons for this and to describe the implications for a patient survey in the ED. METHODS: The development of the questionnaire was based on a literature search and the results of the qualitative EPICS-2 study. Two pretest surveys were conducted in three EDs at the Charité - Universitätsmedizin Berlin. We included patients aged ≥ 18 years with outpatient treatment and the categories blue (nonurgent), green (standard), or yellow (urgent) according to the Manchester Triage System (MTS). RESULTS: In total, 189 patients were recruited in two surveys (pretest 1: n = 89, pretest 2 n = 100). The final questionnaire includes 24 items, which were evaluated and adapted during both pretests. The items evaluate basic clinical characteristics, reasons for choosing the ED, prior contacts in primary care, utilization of primary care after-hours services as well as sociodemographic characteristics. Data from the hospital information system were used to link the survey data with clinical characteristics. CONCLUSIONS: The questionnaire is based on reasons for ED utilization. We recommend the written, self-applied questionnaire for patient surveys with plausibility checks conducted by staff. It is necessary to consider the heterogenic study surroundings in the ED, which requires a lot of flexibility during data collection.

Heavy metal-nucleotide interactions. III. The participation of amino groups in the binding of methylmercury (II) to cytidine and adenosine 5'-phosphate in aqueous solution: studies by Raman difference spectrophotometry.

Raman difference spectrophotometry has been used to study the interaction of CH3Hg(II) with cytidine and Ado-5'-P at high pH. In contrast to the binding reactions which occur at lower pH or in non-aqueous solvents such as dimethyl sulfoxide, a proton is transferred from the amino group; and the complexes are CH3HgCydH-1 and CH3HgAdoH-1-5'-P. The spectra are significantly different from those of the cationic complexes. The integrated intensities of ligand modes which shift upon metalation can be used to measure the concentration of unreacted ligand and consequently the extent of the reaction. Equilibrium constants for the reactions CH3HgOH + L yields CH3HgLH-1 + H2O were estimated to be log KCyd equals 0.63 plus or minus 0.05 and log KAdo-5'-P equals 0.85 plus or minus 0.05, in fair agreement with values determined under very different conditions by ultraviolet spectrophotometry. The vibrational spectrum of the ligand in CH3HgCydH-1 is virtually the same as that of UrdH-1- which is isoelectronic. The spectrum of the ligand in CH3HgAdoH-1-5'-P is more similar to the isoelectronic base InoH-1-than to Ado-5'-P, although the resemblance is not so close as in the CydH-1---UrdH-1-case. The structures of these complexes are discussed on the basis of their vibrational spectra and similarities in the spectra of related compounds. It is concluded that the CH3Hg(II) binds to the amino nitrogen at high pH with both cytidine and Ado-5'-P. In neutral solution with excess CH3Hg(II), metalation occurs on the amino groups, on the ring, and also on the ribose.

Successful treatment of meningeal leukemia using systemic high-dose cytosine arabinoside.

Conventional therapy for leukemic meningitis includes cranial irradiation and intrathecal chemotherapy administered by repeated lumbar punctures or direct intraventricular instillation via an Ommaya reservoir. Several clinical reports have indicated that high doses of cytosine arabinoside (ara-C) are effective in the treatment of acute leukemia refractory to standard induction therapy. Pharmacokinetic studies have demonstrated that high doses of ara-C given intravenously obtain sustained therapeutic drug concentrations in the cerebrospinal fluid, suggesting that this approach may be useful in the treatment of systemic disease associated with meningeal involvement. Five consecutive patients with overt meningeal leukemia were treated using only systemic chemotherapy containing high-dose ara-C. In all patients there was prompt resolution of neurologic symptoms and signs accompanied by cytologic clearing of leukemic cells from the cerebrospinal fluid.

Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.

Successful high-dose intravenous cytarabine treatment of parenchymal brain involvement from malignant lymphoma.

A patient with systemic recurrence of large-cell malignant lymphoma developed radiologic evidence of parenchymal brain metastasis. Treatment with systemic high-dose cytarabine resulted in complete regression of peripheral adenopathy and complete radiologic response in the central nervous system, with normalization of the brain computed tomographic scan. This case further demonstrates the ability of high-dose cytarabine to penetrate the blood-brain barrier and achieve therapeutic drug concentrations in the central nervous system, an area that might otherwise remain a pharmacologic sanctuary for tumor cells.

Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial.

The effectiveness of a ten-day course of either oral bacitracin or oral vancomycin hydrochloride for treatment of Clostridium difficile-induced antibiotic-associated diarrhea was compared in a randomized double-blind study. Bacitracin was as effective as vancomycin in resolving diarrhea; most patients responded within five days of therapy with either drug. Three patients receiving bacitracin worsened during therapy; two of these were considered treatment failures. Neither C difficile nor its toxin was detected in stool samples collected on the final day of therapy in 71% of patients (10/14) receiving vancomycin and in 30% (3/10) receiving bacitracin. Five patients receiving bacitracin and three receiving vancomycin had at least one recurrence. Low but nontoxic concentrations of bacitracin were detected in serum samples collected from 11 patients. Oral bacitracin at this dosage level was as effective as vancomycin in resolving the symptoms of C difficile-induced antibiotic-associated diarrhea in most patients but was less effective in eradicating C difficile and its toxin from patients' stools.

Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis.

Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes.

Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies.

Human testicular androgen-binding protein shares immunodeterminants with serum testosterone-estradiol-binding globulin.

In the human, there are two glycoproteins, testosterone-estradiol-binding globulin (hTeBG) and androgen-binding protein (hABP), which bind testosterone. Although these two proteins have similar physicochemical properties, they can be distinguished on the basis of origin and lectin binding. hTeBG is made in the liver and exhibits high affinity for Concanavalin A (Con A), while hABP from the testes is only partially bound to this lectin. That is, when testicular extracts were applied to Con A-Sepharose columns, a portion of the testosterone-binding material showed no interaction with the lectin and eluted in the void volume (peak I), while the remainder interacted strongly and could be eluted with alpha-methyl-D-glucoside (peak II). These observations are consistent with the proposal that peak I contains only hABP, whereas peak II contains hTeBG and/or hABP with carbohydrate units that permit binding to Con A. To further study the properties of these binding proteins, a hTeBG RIA using a monospecific antiserum was employed to compare the proteins in testes and serum. The results indicated that the testosterone-binding activities in peaks I and II of testicular extracts could not be distinguished immunologically from hTeBG in sera of normal women. These findings suggested that hTeBG and hABP share common epitopes. We next determined whether hABP was secreted into the blood or amniotic fluid by fractionating these fluids in Con A-Sepharose columns. Unlike testicular extracts, male serum and amniotic fluid contained single immunoreactive and steroid-binding species which bound specifically to Con A. We conclude from these observations that hABP (peak I), peak II activity, and hTeBG have common immunodeterminants and that if hABP is secreted into the blood of men, then its carbohydrate chains bind to Con A, making it indistinguishable from hTeBG under these conditions.

Treatment of prostate cancer with gonadotropin-releasing hormone analogue: effect on lipoprotein[a].

Because of its association with cardiovascular disease, lipoprotein[a] (Lp[a]) has attracted the interest of the medical community. Even though serum concentrations of Lp[a] are mainly controlled by the apolipoprotein[a] gene locus, hormonal and metabolic factors, including manipulations of sex hormone levels, have been associated with changes in Lp[a] levels. We report here that the GnRH analog buserelin reduced concentrations of Lp[a] by 48% in elderly males suffering from cancer of the prostate. In contrast, apolipoprotein B levels increased during treatment, whereas other lipid factors, including serum cholesterol, triglyceride, high and low density lipoprotein cholesterol, and apolipoprotein A-I, were not affected. Although the study does not exclude a specific Lp(a)-lowering effect of buserelin, our results suggest that GnRH analogs may reduce Lp[a] levels in the circulation.