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Biomedical subjects

R Herwig

Publications and source records attributed to R Herwig.

At least 19 recordsLinked to original sources

Isolated right-sided varicocele as a salvage pathway for portal hypertension.

Retrograde blood flow can occur in the testicular veins and in the pampiniformis plexus in the absence of valves or if the valves are incompetent, resulting in tortuosity and dilatation of the veins. These abnormal alterations in the anatomy of the veins, termed varicoceles, are associated with infertility in the male. Most varicoceles occur on the left. We report the case of a rare isolated right-sided varicocele in a male evaluated for infertility in whom extensive work-up revealed venous anomalies and a spontaneous porto-systemic shunt. In such cases, standard approaches to infertility treatment are fruitless.

Humans↗

[Transrectal three dimensional sonography. Techniques and indications].

In 3-D transrectal ultrasound it is possible, for the first time, to investigate the region of interest in three planes simultaneously. Exact examination of the organs of the small pelvis as well as of pathologic changes in the region of the pelvic floor can be performed with this new imaging technique. The bulbourethral glands can be investigated routinely, which enables the diagnosis of cysts of these glands. The prostatic zones, their relations as well as the growth of the transitional zone during the development of benign prostatic hyperplasia can be visualized. Furthermore, 3-D transrectal ultrasound allows investigation of morphology and function of the rhabdosphincter. The contractility of the muscle can be quantified. 3-D ultrasound guided puncture and drainage of prostatic abscesses represents a minimally invasive therapeutic modality. This technique can be used to place needles as well as implants in the lower urinary tract. Generally, 3-D transrectal ultrasound offers new diagnostic and therapeutic possibilities.

Animals↗

Late urologic effects after adjuvant irradiation in stage I endometrial carcinoma.

OBJECTIVES: To evaluate the incidence and type of incontinence after external beam radiotherapy (RT) and brachytherapy. Distinct late effects on the urinary bladder can occur and are frequently mild after adjuvant RT for Stage I endometrial carcinoma. Not all side effects that impair quality of life (eg, urinary incontinence) are classified in the commonly used grading system. METHODS: Forty-one patients were evaluated for newly occurred urinary incontinence after adjuvant RT. The mean follow-up was 64.8 months, and the mean age was 62.1 years. The validated incontinence score from Gaudenz was used. Additionally, quality-of-life questions were asked. RESULTS: Overall, 22 (53.7%) of 41 patients complained of urinary incontinence. Urge incontinence was classified in 45.5% (10 of 22 patients) and stress urinary incontinence in 54.5% (12 of 22 patients). CONCLUSIONS: The onset of stress urinary incontinence after brachytherapy can be explained by anatomic findings, such as adverse affects to the nerve supply of the rhabdosphincter. According to our results, the exposure to additional external beam RT can cause urge incontinence. Patients and doctors must be aware that urinary incontinence, with an occurrence rate of more than 50%, represents the most common side effect after surgery and RT for Stage I endometrial carcinoma. We conclude that, depending on the type of RT, a stress incontinence rate of 24.4% and an urge incontinence rate of 29.2% is possible.

Adenocarcinoma↗

Tissue perfusion essential for spermatogenesis and outcome of testicular sperm extraction (TESE) for assisted reproduction.

PURPOSE: In order to determine if there are areas of major and minor perfusion in a single testicle and if the quality of sperm is correlated with quantity of perfusion we collected testicle tissue for TESE in accordance to the local testicle tissue perfusion. METHODS: A patient undergoing TESE underwent testicular perfusion mapping using contrast enhanced ultrasound. The exposed tissue was scanned with a Laser Doppler scanner and perfusion rates were determined measuring tissue perfusion units (TPUs). Tissue was biopsied and sperm were selected and prepared for assisted reproduction. RESULTS: The total amount of isolated sperm correlated highly with the intensity of tissue perfusion showing high number of sperm in areas with high TPUs. CONCLUSIONS: This is the first demonstration that sperm quality and quantity is depending on tissue perfusion within the testicle. To further improve infertility treatment we propose that random biopsies could be replaced by perfusion-dependent collection of testicular tissue.

Biopsy↗

Establishment of T cell-specific and natural killer cell-specific unigene sets: towards high-throughput genomics of leukaemia.

We report the establishment of highly non-redundant unigene sets consisting of cDNA clones derived from T lymphocytes and natural killer cells. Each set consists of 10 506 and 13 409 clones, respectively, arrayed on nylon membranes in duplicate. The sets provide an excellent tool for genome-wide gene expression analysis studies in immunology research.

Blotting, Northern↗

Exploring potential target genes of signaling pathways by predicting conserved transcription factor binding sites.

Many cellular signaling pathways induce gene expression by activating specific transcription factor complexes. Conventional approaches to the prediction of transcription factor binding sites lead to a notoriously high number of false discoveries. To alleviate this problem, we consider only binding sites that are conserved in man-mouse genomic sequence comparisons. We employ two alternative methods for predicting binding sites: exact matches to validated binding site sequences and weight matrix scans. We then ask the question whether there is a characteristic association between a transcription factor or set thereof to a particular group of genes. Our approach is tested on genes, which are induced in dendritic cells in response to the cells' exposure to LPS. We chose this example because the underlying signaling pathways are well understood. We demonstrate the benefit of conserved predicted binding sites in interpreting the LPS experiment. Additionally, we find that both methods for the prediction of conserved binding sites complement one another. Finally, our results suggest a distinct role for SRF in the context of LPS-induced gene expression.

Algorithms↗

Statistical evaluation of differential expression on cDNA nylon arrays with replicated experiments.

In this paper we focus on the detection of differentially expressed genes according to changes in hybridization signals using statistical tests. These tests were applied to 14 208 zebrafish cDNA clones that were immobilized on a nylon support and hybridized with radioactively labeled target mRNA from wild-type and lithium-treated zebrafish embryos. The methods were evaluated with respect to 16 control clones that correspond to eight different genes which are known to be involved in dorso-ventral axis specification. Moreover, 4608 Arabidopsis thaliana clones on the same array were used to judge statistical significance of expression changes and to control the false positive rates of the test decisions. Utilizing this special array design we show that differential expression of a high proportion of cDNA clones (15/16) and the respective genes (7/8) were identified, with a false positive error of <5% using the constant control data. Furthermore, we investigated the influence of the number of repetitions of experiments on the accuracy of the procedures with experimental and simulated data. Our results suggest that the detection of differential expression with repeated hybridization experiments is an accurate and sensitive way of identifying even small expression changes (1:1.5) of a large number of genes in parallel.

Animals↗

Identification of nodal signaling targets by array analysis of induced complex probes.

Nodal signaling controls germ layer formation, left-right asymmetry, and patterning of the brain in the vertebrate embryo. Cellular responses to Nodal signals are complex and include changes in gene expression, cell morphology, and migratory behavior. Only little is known about the genes regulated by Nodal signaling. We designed a subtractive screening strategy by using a constitutively active Nodal receptor to identify putative target genes of Nodal signals in the early gastrula of zebrafish embryos. By quantitative analysis of macro-array hybridizations, 132 genes corresponding to 1.4% of genes on the entire macro-array were identified, which were enriched in the Nodal-induced probe pool. These genes encode components of signal transduction pathways, transcription regulators, proteins involved in protein metabolism but also cytoskeletal components and metabolic enzymes, suggesting dramatic changes of cell physiology in gastrula cells in response to Nodal signals.

Animals↗

Conn's syndrome and bilateral renal artery stenosis in the presence of multiple renal arteries.

We report the case of a 42-year-old male who was admitted to our hospital after an acute hypertensive crisis despite four-way anti-hypertensive therapy. The renal scintigraphy, the excretory urogram and the biochemical profile performed two years before were unremarkable, except for slightly elevated serum creatinine and plasma aldosterone, in presence of normal aldosterone/renin ratio. The renal arterial angiography that was performed despite a second unremarkable scintigraphy revealed high-grade bilateral arterial stenosis in the presence of multiple renal arteries. Following dilatation of the left stenosis, the aldosterone/renin ratio was pathologic. Recumbent and orthostatic aldosterone values were 830 pg/ml and 1824 pg/ml, respectively, and recumbent and orthostatic renin values were 0.82 and 1.21 ng angiotensin I/ml/h, respectively. The abdominal computed tomography performed to investigate a possible concomitant Conn's syndrome resulted in the detection of a left adrenal tumor. After resection of the lesion, plasma-aldosterone levels normalized and a pronounced rise in serum potassium levels was observed. Following angioplasty of the right renal artery stenosis, blood pressure could easily be managed with combined beta and calcium channel blocker therapy. Particularly in cases of bilateral (but also in the presence of unilateral) renal artery stenosis in association with Conn's syndrome, all the available screening methods for these disorders can fail. In cases of poor response to combination hypertensive therapies, renal arteriography and a fludrocortisone-suppression test should be performed in order to rule out both renal arterial stenosis and Conn's syndrome, even in the absence of clinical and biochemical findings suspicious for either disorder.

Adult↗

An oligonucleotide fingerprint normalized and expressed sequence tag characterized zebrafish cDNA library.

The zebrafish is a powerful system for understanding the vertebrate genome, allowing the combination of genetic, molecular, and embryological analysis. Expressed sequence tags (ESTs) provide a rapid means of identifying an organism's genes for further analysis, but any EST project is limited by the availability of suitable libraries. Such cDNA libraries must be of high quality and provide a high rate of gene discovery. However, commonly used normalization and subtraction procedures tend to select for shorter, truncated, and internally primed inserts, seriously affecting library quality. An alternative procedure is to use oligonucleotide fingerprinting (OFP) to precluster clones before EST sequencing, thereby reducing the re-sequencing of common transcripts. Here, we describe the use of OFP to normalize and subtract 75,000 clones from two cDNA libraries, to a minimal set of 25,102 clones. We generated 25,788 ESTs (11,380 3' and 14,408 5') from over 16,000 of these clones. Clustering of 10,654 high-quality 3' ESTs from this set identified 7232 clusters (likely genes), corresponding to a 68% gene diversity rate, comparable to what has been reported for the best normalized human cDNA libraries, and indicating that the complete set of 25,102 clones contains as many as 17,000 genes. Yet, the library quality remains high. The complete set of 25,102 clones is available for researchers as glycerol stocks, filters sets, and as individual EST clones. These resources have been used for radiation hybrid, genetic, and physical mapping of the zebrafish genome, as well as positional cloning and candidate gene identification, molecular marker, and microarray development.

Animals↗

Clinical differences between benign and malignant pheochromocytomas.

Most pheochromocytomas can be cured by resection. In view of the unfavourable prognosis for surgical therapy in cases of late tumour detection and malignant tumours, the aim of the present study is to differentiate between typical signs and symptoms of malignant versus benign pheochromocytomas. We investigated the records of 133 patients retrospectively (1967-1998). In cases of benign tumours (104 of 133, mean age 42+/-15.8 years) tumour size was 5.9+/-3.4 cm, and history was 47.4+/-75.4 months. 7.7% of the tumours were extraadrenal, and 77% had paroxysmal manifestations. The other 29 patients (mean age: 39.2+/-21.9 years) had malignant lesions (tumour size: 9.4+/-5.9 cm (p=0.0022); history: 7.4+/-5.6 months (p=0.0137); extraadrenal: 24.1% (p=0.0219); paroxysmal: 37.9% (p=0.0012)). Symptoms of patients with benign tumours were hypertension (80%), headaches (42.3%), sweating (30.8%), tachycardia (26%) and pallor (24%) (Malignant: Hypertension 46%, p=0.0873; headaches 11%, p=0.0008; sweating 11%, p=0.0196; tachycardia 14%, p=0.1961 and pallor 0%, p=0.0010). Abdominal pain and dorsalgia occurred more frequently in malignant pheochromocytomas (26% versus 7%, p=0.0014). Unusually short histories and extraadrenal localization appear to be suspicious for malignancy. The "typical" clinical signs and symptoms occur more frequently in patients with benign tumours and can therefore be regarded as typical signs of benign pheochromocytomas.

Abdominal Pain↗

New tools for oligonucleotide fingerprinting.

Oligonucleotide fingerprinting is an attractive, high-throughput complement to tag sequencing methods to determine the spectrum and abundance of genes in cDNA libraries. This method currently relies on the sequential hybridizations of short, radioactively labeled DNA oligonucleotides to clone arrays. Here, we describe a new environment that substantially improves this technology. Fluorescently labeled peptide nucleic acid (PNA) oligonucleotides are used as hybridization probes. Hybridization results are recorded with a large-field, high-resolution laser scanner developed for this purpose. Automated image analysis allows easy handling of large numbers of hybridization images. Signal interference effects, which limit the gridding density in the radioactive approach, are strongly reduced. The sensitivity of the fluorescence detection demonstrated permits the convenient use of nylon membranes. Hybridization data quality is improved, and its generation is substantially accelerated, simplified, and less expensive.

Autoanalysis↗

Pure primary choriocarcinoma of the urinary bladder with long-term survival.

Choriocarcinoma was diagnosed in a 77-year-old woman with an acute massive, painless hematuria. One year after anterior pelvic exenteration and ileal conduit, the beta-human chorionic gonadotropin level increased to 934 mIU/mL without any sign of tumor progression. After six courses of chemotherapy (vincristine, actinomycin, and cyclophosphamide), the beta-human chorionic gonadotropin levels returned to normal. To our knowledge, this is the fourth case of pure choriocarcinoma in the bladder, with the longest survival time of 33 months so far.

Aged↗

[Diagnosis of interstitial cystitis].

Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects.

Biopsy↗

[Endourological surgical techniques in interstitial nephritis].

Endourological surgical procedures (transurethral resection and fulguration, Nd-YAG-laser application) for the treatment of interstitial cystitis (IC) have been evaluated only in a few studies. Theoretically, they could be the next step in a therapeutic concept after conservative measures have failed and before open surgery is performed as an ultima ratio. However, our review of the literature suggests that to date there is no scientific evidence to support endourological techniques in the treatment of IC.

Cystoscopy↗

[Alternative and complementary therapeutic measures in interstitial cystitis].

Alternative therapies are gaining more and more popularity. Mostly, these methods are demanded by patients who are not effectively relieved by allopathy. This review points out alternative and additive methods that have been repeatedly described as effective as additional supportive treatments of interstitial cystitis.

Complementary Therapies↗

Information theoretical probe selection for hybridisation experiments.

MOTIVATION: The choice of probes is an important feature of hybridisation experiments. In this paper we present an algorithm that optimises probes with respect to a training set of sequences based on Shannon entropy as a quality criterion. The practical motivation for our algorithm is oligonucleotide fingerprinting, a method for the simultaneous identification of sequences (cDNA or genomic DNA) by their hybridisation tags according to a set of short probes such as octamers, although the algorithm is of course not restricted to that application. RESULTS: We can show that our method is superior to the selection of probes according to their frequencies, which is a widely used strategy, and to randomly chosen probe sets. The quality of probe sets is assessed by a simulation pipeline that entails the set of probes as a simulation parameter. The performance of probe sets trained on sequences from different organisms shows additionally that probes should be chosen with regard to the organism under analysis. Case studies are presented on how constraints (G+C-content, complexity of the individual probes) influence the selection process. AVAILABILITY: A description of the oligonucleotide fingerprinting pipeline is published on our web-page http://www.molgen.mpg.de/ approximately ag_onf/met.htm. An executable of the algorithm and probe lists designed for human and rodents can be downloaded from the ftp-site ftp://ftp.molgen.mpg.de/pub/mpimg/probe_design/.

Algorithms↗