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Biomedical subjects

Frank Sommer

Publications and source records attributed to Frank Sommer.

At least 19 recordsLinked to original sources
PubMed2007

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial.

AIM: To test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment. METHODS: In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy. RESULTS: After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized. CONCLUSION: Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Adult↗
PubMed2006

Patients responding to phosphodiesterase type 5 inhibitor therapy: what do their sexual partners know?

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are an efficacious therapy in men with erectile dysfunction (ED). There are only a few studies that also focus on the participating couples during PDE5 inhibitor therapy. AIM: To determine to what extent patients personally informed their sexual partners about their ongoing PDE5 inhibitor therapy. MAIN OUTCOME MEASURES: Likelihood of informing the female partner by the patient himself about the use of PDE5 inhibitors. METHODS: A total of 216 men (mean age 62.3 years) with ED were successfully treated with PDE5 inhibitors in three independent centers. After an interval of at least 3 months of successful ED therapy, all patients were asked by questionnaire whether their sexual partners were informed of their PDE5 inhibitor therapy. RESULTS: Eighty-two percent of the patients were exclusively involved in one stable sexual relationship, 9.7% of the men admitted to having changing sexual partners, and 6% did not give any information at all about their sexual partners. Twenty percent of the men had a severe ED (International Index of Erectile Function [IIEF-5] <11). Forty-nine percent showed a moderate ED (IIEF-5 11-16) and 31% suffered a mild ED (IIEF-5 >16). PDE5 inhibitor medication was used 1.2 times/month by men with a severe ED, 2.1 times/month by patients with a moderate ED, and 2.9 times/month by men with a mild ED. Forty-one (93%) of the 44 patients with a severe ED informed their sexual partners that they were taking PDE5 inhibitors. In the patient group with moderate ED, 49 (47%) of 105 patients and only 14 (21%) of 67 of the patients with mild ED shared this information with their partners. CONCLUSION: Less than 40% of the patients suffering a moderate or mild ED using PDE5 inhibitors shared this information with their partners. It seems that patients find ED so disturbing that many patients do not inform their partners of PDE5 inhibitor use.

Aged↗
PubMed2006

C20 carbon clusters: fullerene-boat-sheet generation, mass selection, photoelectron characterization.

Electron-impact ionization in a time-of-flight mass spectrometer of C(20)H(0-3)Br(14-12) probes-secured from C(20)H(20) dodecahedrane by a "brute-force" bromination protocol-provided bromine-free C(20)H(0-2(3)) anions in amounts that allowed the clean mass-separation of the hydrogen-free C(20) (-) ions and the photoelectron (PE) spectroscopic characterization as C(20) fullerene (electron affinity (EA)=2.25+/-0.03 eV, vibrational progressions of 730+/-70). The extremely strained C(20) fullerene ions surfaced as kinetically rather stable entities (lifetime of at least the total flight time of 0.4 ms); they only very sluggishly expel a C(2) unit. The HOMO and LUMO are suggested to be almost degenerate (DeltaE=0.27 eV). The assignment as a fullerene was corroborated by the PE characterization of the C(20) bowl (EA=2.17+/-0.03 eV, vibrational progression of 2060+/-50 cm(-1)) analogously generated from C(20)H(10) corannulene (C(20)H(1-3)Br(9-8) samples) and comparably stable. Highly resolved low-temperature PE spectra of the known C(20) ring (EA=2.49+/-0.03 eV, vibrational progressions 2022+/-45 and 455+/-30 cm(-1)), obtained from graphite, display an admixture of, most probably, a bicyclic isomer (EA=3.40+/-0.03 eV, vibrational progression 455+/-30 cm(-1)). The C(20) (+(-)) and C(20)H(2) (+(-)) cluster ions generated from polybrominated perylene (C(20)H(0-2)Br(12-10)) have (most probably) retained the planar perylene-type skeleton (sheet, EA=2.47+/-0.03 eV, vibrational progressions of 2089+/-30 and 492+/-30 cm(-1) and EA=2.18+/-0.03 eV, vibrational progressions of 2105+/-30 and 468+/-30 cm(-1)).

Alkynes↗
PubMed2006

Evaluation of tetrahydrobiopterin (BH4) as a potential therapeutic agent to treat erectile dysfunction.

AIM: Nitric oxide (NO)-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase (eNOS) coenzyme tetrahydrobiopterin (BH4) converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation. METHODS: Using quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction (ED) while receiving visual sexual stimulation. RESULTS: 8-Isoprostane content in endothelium and smooth muscle was significantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of > 60% penile rigidity (33.5 min [95% confidence interval (CI): 13.1-49.3] at base and 29.4 min [95% CI: 8.9-42.2] at tip). A 500-mg dose increased the relative duration of > 60% penile rigidity by 36.1 min (95% CI: 16.3-51.8) at the base and 33.7 min (95% CI: 11.4-43.9) at the tip. Treatments were well tolerated. CONCLUSION: BH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS.

Adolescent↗
PubMed2005

Cladocerans versus copepods: the cause of contrasting top-down controls on freshwater and marine phytoplankton.

Top-down control of phytoplankton by crustacean mesozooplankton is a cornerstone of freshwater ecology. Apparently, trophic cascades are more frequently reported from freshwater than from marine plankton. We argue that this difference is real and mainly caused by biological differences at the zooplankton-phytoplankton link: cladocerans (particularly Daphnia) in the lakes and copepods in the sea. We derive these conclusions from recent literature and a number of own, similarly designed mesocosm experiments conducted in a lake, a brackish water and a marine site. In all experiments, phytoplankton were exposed to gradients of experimentally manipulated densities of zooplankton, including freshwater copepods and cladocerans, and marine copepods and appendicularians. The suggested reasons for the difference between lake and marine trophic cascades are: (1) Both copepods and cladocerans suppress only part of the phytoplankton size spectrum: cladocerans the small and copepods the large phytoplankton. (2) If not controlled by grazing, small phytoplankton may increase their biomass faster than large phytoplankton. (3) Copepods additionally release small phytoplankton from grazing pressure by intermediate consumers (protozoa) and competitors (predation on appendicularian eggs), while cladocerans do not release large phytoplankton from grazing pressure by any functional group. (4) Cladocerans sequester more of the limiting nutrient than copepods, leaving fewer nutrients available for compensatory growth of ungrazed phytoplankton.

Animals↗
PubMed2005

Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors.

A large body of evidence has accumulated demonstrating that a common pathway in conditions such as hypertension, atherosclerosis, hypercholesterolemia, diabetes mellitus, and erectile dysfunction (ED) is endothelial dysfunction. Although a complete pharmacological cure for ED is currently unavailable, the phosphodiesterase 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are efficacious oral therapy for ED. Results from recent studies suggest that regular treatment with a PDE5 inhibitor may lead to enhanced erectile function (EF) beyond that observed with on-demand usage, possibly through improvement of endothelial function. Such an effect may be viewed as rehabilitation of damaged erectile tissue. The present review focuses on several recent studies which provide evidence for the beneficial effect of regular PDE5 inhibitor administration on the improvement of EF by rehabilitation of vascular endothelium.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Differential endostatin binding to bladder, prostate and kidney tumour vessels.

OBJECTIVES: To define the anti-angiogenic mechanism and causes of the heterogeneous influence of endostatin, one of a group of matrix-derived inhibitors of tumour angiogenesis of increasing significance in tumour treatment, on various tissue types. MATERIALS AND METHODS: Variations in the binding behaviour of endostatin with vessels were assessed in different tumours (bladder, prostate and kidney) and compared with benign tissue vessels. Biotinylated endostatin was used and detected using extravidin CY3 and extravidin-gold immunolabelling. RESULTS: There were significant differences in the number of vessels showing endostatin binding among benign and malignant bladder, prostate and kidney tissues. While there was distinct endostatin binding on a mean (sd) of 94.2 (3.0)% bladder and 73.8 (19.5)% prostate tumour vessels, there was less binding, at 11.32 (3.9)%, on kidney tumour vessels. There was less binding to vessels of benign bladder, prostate and kidney tissue, at 2.0 (1.5), 1.7 (1.7) and 1.5 (1.7)%, respectively. At the ultrastructural level, different binding sites were detected both inside and outside the endothelial cells. CONCLUSION: Endostatin binds more to all tumour tissues than to benign tissue, but the degree of binding in malignant kidney tissue was significantly less than that in malignant prostate and bladder tissues. These divergent vascular endostatin-binding patterns could be responsible for a tumour type-dependent anti-angiogenic effect attributable to endostatin. Such selective behaviour would have therapeutic consequences for future anti-angiogenic therapy, in which different kinds of tumours could be further classified into those responding to endostatin or not.

Aged↗
PubMed2005

Potency and selectivity of vardenafil: a phosphodiesterase Type 5 inhibitor.

Erectile dysfunction (ED) is a widespread, age-related medical condition that affects > 50% of men aged 40 - 70 years. Pharmacotherapy with orally available phosphodiesterase 5 (PDE5) inhibitors offers a convenient and simple approach to treatment. Results of numerous clinical trials have demonstrated significant efficacy in restoring the ability to achieve and sustain an erection, and adverse side effects are generally mild-to-moderate in severity. Vardenafil is a highly selective, potent PDE5 inhibitor developed for the treatment of ED. The potency and selectivity of vardenafil for PDE5 and other PDE isoforms have been evaluated in vitro and in vivo and compared with other compounds in the class. This review will discuss the findings of biochemical, in vitro and in vivo experiments that indicate the superior potency and high selectivity of vardenafil.

Animals↗
PubMed2004

Prospective randomized Phase II trial of pegylated doxorubicin in the management of symptomatic hormone-refractory prostate carcinoma.

BACKGROUND: Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone-refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent. METHODS: Forty-eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty-eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate-specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: The median patient age was 68.9 years (range, 58-79 years), and the mean follow-up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8-6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1-year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar-plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose-limiting cardiotoxicities or hematotoxicities were documented. CONCLUSIONS: Pegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin-containing combination regimens for patients with HRPCA.

Aged↗
PubMed2004

Enhanced TCR-induced apoptosis in interferon regulatory factor 4-deficient CD4(+) Th cells.

Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4(+) T helper (Th) cells lacking IRF4 (IRF4(-/-)) are highly sensitive to apoptosis. After infection of IRF4(-/-) mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4(-/-) CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4(+) cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4(-/-) and IRF4(+/+) cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+) cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central in protecting CD4(+) cells against proapoptotic stimuli.

Animals↗
PubMed2004

Vessels in benign prostatic hyperplasia contain more binding sites for endostatin than vessels in normal prostate tissue.

OBJECTIVE: The angiogenic phenotype is an effect of a net balance of angiogenic and anti-angiogenic factors. Endostatin is one of a group of recently described matrix-derived inhibitors of tumour angiogenesis that have acquired increasing significance for tumour treatment. Endostatin's anti-angiogenic mechanism and the causes of its heterogenic influence on various tissue types have not yet been defined. METHODS: We investigated the variations in endostatin's binding behaviour to vessels in benign prostatic hyperplasia (BPH) compared to endostatin binding to vessels in normal prostate tissue. Biotinylated endostatin was used and was detected using Extravidin CY3. RESULTS: In BPH 89.12% +/- 10.72% of vessels showed endostatin binding. This was significantly more than observed for vessels in normal prostate tissue (1.66% +/- 1.66%). CONCLUSION: The strongly proliferative tissue of BPH may be a growth-limited cause of significantly more endostatin binding sites. The investigation indicates endostatin as a possible new target for BPH treatment.

Aged↗
PubMed2004

The influence of mesozooplankton on phytoplankton nutrient limitation: a mesocosm study with northeast Atlantic plankton.

We used marine phytoplankton from mesocosms seeded with different zooplankton densities to study the impact of mesozooplankton on phytoplankton nutrient limitation. After 7 d of grazing (copepod mesocosms) or 9 d (appendicularian mesocosms) phytoplankton nutrient limitation was studied by enrichment bioassays. After removal of mesozooplankton, bioassay bottles received either no nutrients, phosphorus or nitrogen alone, or a combination of nitrogen and phosphorus and were incubated for 2 d. Phytoplankton reproductive rates in the bottles without nutrient addition were calculated after correction for grazing by ciliates and indicated increasing nitrogen limitation with increasing copepod abundance. No nutrient limitation was found in the appendicularian mesocosms. The increase of nutrient limitation with increasing copepod density seems to be mainly the result of a trophic cascade effect: Copepods released nanoplankton from ciliate grazing pressure, and thereby enhanced nitrogen exhaustion by nanophytoplankton and reduced nitrogen excretion by ciliates. Nitrogen sequestration in copepod biomass, the mechanism predicted by the ecological stoichiometry theory, seems to have been a weaker effect because there was only little copepod growth during the experiment.

Animals↗
PubMed2004

Systemic Th1 immunization of mice against Helicobacter pylori infection with CpG oligodeoxynucleotides as adjuvants does not protect from infection but enhances gastritis.

Recent reports have suggested that oral vaccination of mice against Helicobacter pylori is dependent on a Th1-mediated immune response. However, oral vaccination in mice neither induces sterilizing immunity nor leads to complete protection from disease. Therefore, in this study we investigated whether a systemic subcutaneous immunization against H. pylori by using CpG oligodeoxynucleotides as a Th1 adjuvant could achieve protection in a mouse model of H. pylori infection. CpG oligodeoxynucleotides are known for their ability to induce nearly entirely Th1-biased immune responses and may be approved for human use in future. Immunization of mice with H. pylori lysate and CpG induced a strong local and systemic Th1 immune response. Despite this strong Th1 response, mice were not protected from infection with H. pylori yet had a 10-fold reduction in the number of H. pylori in the gastric mucosa compared to nonimmunized mice. Of note, reduction of the bacterial density in immunized mice was accompanied by a significantly enhanced gastritis. Hence, systemic Th1 immunization of mice, even though being able to reduce the bacterial load in the stomach, is associated with aggravated pathology.

Adjuvants, Immunologic↗
PubMed2004

Future options for combination therapy in the management of erectile dysfunction in older men.

The prevalence of erectile dysfunction (ED) has dramatically increased in parallel with the aging of the Western industrialised population. The estimated prevalence of ED worldwide in 1995 was 152 million men. As the population in industrial nations ages, an estimated 322 million men will be affected by ED by the year 2025. Oral drug therapy with the phosphodiesterase (PDE) type 5 inhibitor sildenafil fails in some patients with ED; however, several different classes of drugs demonstrate efficacy in treating ED, creating the potential for pharmacological combination therapy. Pharmaceutical products that lead to the activation of or an increase in cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate), with or without nitric oxide donors or nitrates, as well as alpha-adrenoceptor antagonists, have been used to treat ED. Sildenafil has been used in combination with alprostadil (prostaglandin E1) and administered via intraurethral or intracavernous route. Successful intercourse using this combination of agents varies from 47% to 100% following failed monotherapy. Various combination therapies for ED are being studied using PDE5 inhibitors, together with other agents, alpha-adrenoceptor antagonists, and testosterone replacement therapy for men with hypogonadism. The combination of centrally acting agents with PDE5 inhibitors, e.g. a regimen of apomorphine plus PDE5 inhibitor, is an attractive approach because the two therapies target different mechanisms. New PDE5 inhibitors such as vardenafil should be tried first as therapy for sildenafil nonresponders before exploring any combination therapy options. Preliminary observations of combination therapy have been encouraging and provide a scientific rationale for prospective, randomised clinical trials with adequate numbers of patients.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Lifestyle issues and genitourinary tumours.

A variety of lifestyle factors, including physical activity, artificial sweeteners, alcohol consumption and smoking, have been reported to contribute to the risk of developing urological malignancies. A great number of epidemiological studies suggest that sports and physical activity may have a preventive influence on genitourinary tumours, especially on the incidence of prostate cancer. Smoking appears to be the most relevant lifestyle factor significantly increasing both incidence and mortality from bladder cancer. Furthermore, there is evidence implicating an association between tobacco use and kidney cancer. In contrast, prostate and testicular cancers are unlikely to be linked to tobacco use. As far as alcohol is concerned, most studies indicate that neither amount nor type of alcohol seems to be clearly associated with a risk of developing urological malignancies. However, some more recent cohort studies suggest a moderately increased risk for prostate and bladder cancer for specific types of alcohol. On the other hand, there is evidence that moderate alcohol consumption may even protect women from developing renal cancer. Since the introduction of artificial sweeteners, reports of potential cancer risks have circulated periodically through the mass media. The wide distribution of these agents and the fact that mostly combinations of the different compounds are added to a broad variety of food, drinks, drugs, and hygiene products complicates a systematic analysis of their potential impact on the development of urological malignancies. Nevertheless, so far not a single study has convincingly demonstrated a statistically significant risk of bladder cancer due to the consumption of artificial sweeteners. This survey demonstrates that the individual assessment of lifestyle factors not only may identify groups with an increased risk for urological malignancies but also clearly displays a potential for tumour prevention.

Alcohol Drinking↗
PubMed2003

Daphnia versus copepod impact on summer phytoplankton: functional compensation at both trophic levels.

Here we report on a mesocom study performed to compare the top-down impact of microphagous and macrophagous zooplankton on phytoplankton. We exposed a species-rich, summer phytoplankton assemblage from the mesotrophic Lake Schöhsee (Germany) to logarithmically scaled abundance gradients of the microphagous cladoceran Daphnia hyalinaxgaleata and of a macrophagous copepod assemblage. Total phytoplankton biomass, chlorophyll a and primary production showed only a weak or even insignificant response to zooplankton density in both gradients. In contrast to the weak responses of bulk parameters, both zooplankton groups exerted a strong and contrasting influence on the phytoplankton species composition. The copepods suppressed large phytoplankton, while nanoplanktonic algae increased with increasing copepod density. Daphnia suppressed small algae, while larger species compensated in terms of biomass for the losses. Autotrophic picoplankton declined with zooplankton density in both gradients. Gelatinous, colonial algae were fostered by both zooplankton functional groups, while medium-sized (ca. 3,000 microm3), non-gelatinous algae were suppressed by both. The impact of a functionally mixed zooplankton assemblage became evident when Daphnia began to invade and grow in copepod mesocosms after ca. 10 days. Contrary to the impact of a single functional group, the combined impact of both zooplankton groups led to a substantial decline in total phytoplankton biomass.

Animals↗