Visualization of spatial and temporal temperature distributions with magnetic particle imaging for liver tumor ablation therapy.

Temperature-resolved magnetic particle imaging (MPI) represents a promising tool for medical imaging applications. In this study an approach based on a single calibration measurement was applied for highlighting the potential of MPI for monitoring of temperatures during thermal ablation of liver tumors. For this purpose, liver tissue and liver tumor phantoms embedding different superparamagnetic iron oxide nanoparticles (SPION) were prepared, locally heated up to 70 °C and recorded with MPI. Optimal temperature MPI SPIONs and a corresponding linear model for temperature calculation were determined. The temporal and spatial temperature distributions were compared with infrared (IR) camera results yielding quantitative agreements with a mean absolute deviation of 1 °C despite mismatches in boundary areas.

First magnetic particle imaging angiography in human-sized organs by employing a multimodal ex vivo pig kidney perfusion system.

OBJECTIVE: Magnetic particle imaging (MPI) is a new, fast 3D imaging technique, which is considered promising for angiographies. As available MPI scanners suffer from restricted spatial resolution and are mostly constructed for small animal imaging, no vessels within one organ have been depicted by MPI, yet. The purpose of this study was to develop an ex vivo organ perfusion system to display vessels within one organ of human size by MPI and to compare the results to an established 3D imaging technique. APPROACH: An ex vivo porcine kidney perfusion system compatible with digital subtraction angiography (DSA), magnetic resonance tomography and MPI was developed. DSA was used to exemplarily prove intact vessel structures under ex vivo perfusion in two organs. Perfusion in nine organs was displayed by the 3D imaging techniques magnetic resonance angiography (MRA) and MPI angiography. All visible vessels in MRA and MPI were counted and their number compared between both techniques. MAIN RESULTS: The ex vivo organ perfusion system allowed us to perform angiographies by DSA, MRA and MPI. With it, organs of human size could be imaged in small animal scanners, which permitted us to depict vessels within one organ by MPI for the first time. In comparison to MRA, 33% of all vessels were visible in MPI, a difference probably caused by restricted spatial resolution in MPI. SIGNIFICANCE: The presented ex vivo organ perfusion system can serve to practically evaluate MPI's potential for angiography in human-sized organs. This is especially relevant as long as available, for angiography-suited MPI scanners still suffer from size and spatial resolution restrictions.

In vivo liver visualizations with magnetic particle imaging based on the calibration measurement approach.

Magnetic particle imaging (MPI) facilitates the rapid determination of 3D in vivo magnetic nanoparticle distributions. In this work, liver MPI following intravenous injections of ferucarbotran (Resovist®) was studied. The image reconstruction was based on a calibration measurement, the so called system function. The application of an enhanced system function sample reflecting the particle mobility and aggregation status of ferucarbotran resulted in significantly improved image reconstructions. The finding was supported by characterizations of different ferucarbotran compositions with the magnetorelaxometry and magnetic particle spectroscopy technique. For instance, similar results were obtained between ferucarbotran embedded in freeze-dried mannitol sugar and liver tissue harvested after a ferucarbotran injection. In addition, the combination of multiple shifted measurement patches for a joint reconstruction of the MPI data enlarged the field of view and increased the covering of liver MPI on magnetic resonance images noticeably.

Geometry planning and image registration in magnetic particle imaging using bimodal fiducial markers.

PURPOSE: Magnetic particle imaging (MPI) is a quantitative imaging modality that allows the distribution of superparamagnetic nanoparticles to be visualized. Compared to other imaging techniques like x-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI), MPI only provides a signal from the administered tracer, but no additional morphological information, which complicates geometry planning and the interpretation of MP images. The purpose of the authors' study was to develop bimodal fiducial markers that can be visualized by MPI and MRI in order to create MP-MR fusion images. METHODS: A certain arrangement of three bimodal fiducial markers was developed and used in a combined MRI/MPI phantom and also during in vivo experiments in order to investigate its suitability for geometry planning and image fusion. An algorithm for automated marker extraction in both MR and MP images and rigid registration was established. RESULTS: The developed bimodal fiducial markers can be visualized by MRI and MPI and allow for geometry planning as well as automated registration and fusion of MR-MP images. CONCLUSIONS: To date, exact positioning of the object to be imaged within the field of view (FOV) and the assignment of reconstructed MPI signals to corresponding morphological regions has been difficult. The developed bimodal fiducial markers and the automated image registration algorithm help to overcome these difficulties.

Increasing the sensitivity for stem cell monitoring in system-function based magnetic particle imaging.

The use of superparamagnetic iron oxide nanoparticles (SPIONs) has provided new possibilities in biophysics and biomedical imaging technologies. The magnetization dynamics of SPIONs, which can be influenced by the environment, are of central interest. In this work, different biological SPION environments are used to investigate three different calibration methods for stem cell monitoring in magnetic particle imaging. It is shown that calibrating using SPIONs immobilized via agarose gel or intracellular uptake results in superior stem cell image quality compared to mobile SPIONs in saline. This superior image quality enables more sensitive localization and identification of a significantly smaller number of magnetically labeled stem cells. The results are important for cell tracking and monitoring of future SPION based therapies such as hyperthermia based cancer therapies, targeted drug delivery, or tissue regeneration approaches where it is crucial to image a sufficiently small number of SPIONs interacting with biological matter.

Multimodal Imaging in Neurofibromatosis Type 1-associated Nerve Sheath Tumors.

UNLABELLED: Neurofibromatosis type 1 (NF1) is a neurogenetic disorder. Individuals with NF1 may develop a variety of benign and malignant tumors of which peripheral nerve sheath tumors represent the most frequent entity. Plexiform neurofibromas may demonstrate a locally destructive growth pattern, may cause severe symptoms and may undergo malignant transformation into malignant peripheral nerve sheath tumors (MPNSTs). Whole-body magnetic resonance imaging (MRI) represents the reference standard for detection of soft tissue tumors in NF1. It allows for identification of individuals with plexiform neurofibromas, for assessment of local tumor extent, and for evaluation of whole-body tumor burden on T2-weighted imaging. Multiparametric MRI may provide a comprehensive characterization of different tissue properties of peripheral nerve sheath tumors, and may identify parameters associated with malignant transformation. Due to the absence of any radiation exposure, whole-body MRI may be used for serial follow-up of individuals with plexiform neurofibromas. (18)F-fluorodeoxyglucose positron-emission-tomography (FDG PET/CT) allows a highly sensitive and specific detection of MPNST, and should be used in case of potential malignant transformation of a peripheral nerve sheath tumor. PET/CT provides a sensitive whole-body tumor staging. The use of contrast-enhanced CT for diagnosis of peripheral nerve sheath tumors is limited to special indications. To obtain the most precise readings, optimized examination protocols and dedicated radiologists and nuclear medicine physicians familiar with the complex and variable morphologies of peripheral nerve sheath tumors are required. KEY POINTS: Individuals with NF1 may develop benign and malignant nerve sheath tumors. Whole-body MRI is the reference standard to identify nerve sheath tumors in NF1. MRI provides a comprehensive characterization of the growth pattern, growth dynamics and extent of nerve sheath tumors. (18)F-FDG PET/CT provides a sensitivity of 100% and a specificity of 77-95% for detection of malignant transformation.

One-pot synthesis of magnetite nanorods/graphene composites and its catalytic activity toward electrochemical detection of dopamine.

Magnetite (Fe3O4) nanorods anchored over reduced graphene oxide (rGO) were synthesized through a one-pot synthesis method, where the reduction of GO and in-situ generation of Fe3O4 nanorods occurred concurrently. The average head and tail diameter of Fe3O4 nanorods anchored over the rGO matrix are found to be 32 and 11 nm, respectively, and morphology, structure and diameter of bare Fe3O4 nanorods were not altered even after the composite formation with rGO. The increased structural disorders and decrement in the sp(2) domains stimulated the high electrical conductivity and extended catalytic active sites for the prepared rGO/Fe3O4 nanocomposite. The constructed rGO/Fe3O4/GCE sensor exhibited excellent electrocatalytic activity toward the electrooxidation of dopamine (DA) with a quick response time of 6s, a wide linear range between 0.01 and 100.55 µM, high sensitivity of 3.15 µA µM(-1) cm(-2) and a lower detection limit of 7 nM. Furthermore, the fabricated sensor exhibited a practical applicability in the quantification of DA in urine samples with an excellent recovery rate. The excellent electroanalytical performances and straight-forward, surfactant and template free preparation method construct the rGO/Fe3O4 composite as an extremely promising material for the diagnosis of DA related diseases in biomedical applications.

Age-related differences in the activity of arterial mineral deposition and regional bone metabolism: a 18F-sodium fluoride positron emission tomography study.

UNLABELLED: Functional (18)F-fluoride PET demonstrated an inverse relationship between the activity of arterial mineral deposition and regional bone metabolism. While bone metabolism decreases with age, the activity of arterial mineral deposition increases. INTRODUCTION: The extent of arterial calcification increases with age, whereas bone mineral density decreases, evidencing a well-known inverse correlation on morphological basis. The aim of this study was to evaluate the functional relationship between the activity of arterial mineral deposition and regional bone metabolism as assessed by (18)F-sodium fluoride (NaF) PET/CT. METHODS: Three hundred four subjects were examined by (18)F-NaF PET/CT. Tracer accumulation in the femoral arteries was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio). Uptake was compared with cardiovascular risk factors (RFs), calcified plaque burden, and regional bone metabolism as assessed by PET/CT. RESULTS: The activity of arterial mineral deposition significantly increased with age (p < 0.001), whereas regional bone metabolism significantly decreased (p < 0.001). There was a significant inverse correlation between bone metabolism and arterial mineral deposition (unadjusted, p < 0.001); that association was not significant (p = 0.79) when controlled for age and other RFs. Both high activity of arterial mineral deposition and low bone metabolism were significantly associated with cardiovascular events and other RFs. CONCLUSION: (18)F-NaF PET/CT provides a tool to visualize and quantify the activity of arterial mineral deposition and regional bone metabolism. In this study, we observed an inverse correlation between the activity of arterial mineral deposition and regional bone metabolism. While the activity of arterial mineral deposition significantly increases with age, regional bone metabolism decreases.

Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice.

PURPOSE: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. MATERIALS AND METHODS: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. RESULTS: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ±â€Š1.2 (n1), 9.0 ±â€Š3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ±â€Š3.1 (n1), 22.0 ±â€Š6.1 (n2) and 89.8 ±â€Š6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. CONCLUSION: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. KEY POINTS: • Detection of single magnetically labeled MSC in-vivo using a clinical 3.0 T MRI is possible.• Fluorescent and magnetic co-labeling does not affect cell vitality.• The number of cells detected by MRI and histology has a high correlation.

Expression of macrophage surface markers in induced sputum of patients with chronic obstructive pulmonary disease.

The aim of our study was to evaluate cellular content in induced sputum in chronic obstructive pulmonary disease (COPD) in relation to the degree of airway obstruction, macrophage count, and phenotype. We compared the proportion of macrophages and cells expressing the following markers: CD11b, CD14, CD54, and CD71 in induced sputum obtained from patients with mild-to-moderate and severe COPD (n=29)], asymptomatic smokers (n=18), and nonsmokers (n=18). The differential cell count and macrophage phenotypes were examined in induced sputum by immunocytochemistry. We observed a greater proportion of neutrophils and eosinophils and an elevated macrophage count in patients with COPD and in smokers in comparison with nonsmokers. Macrophages in patients with severe airway obstruction were characterized by a significantly elevated expression of CD11b and CD14 markers. There were higher proportions of macrophages with expression of CD11b, CD14, CD54, and CD71 in induced sputum of smokers in comparison with nonsmokers. We concluded that macrophages are the cells involved in the inflammatory process caused by smoking in COPD. The macrophage phenotype with elevated CD11b and CD14 expressions was associated with severe airflow limitation.

Hematopoietic recovery after IEV chemotherapy for malignant lymphoma followed by different cytokines can be monitored by analysis of Galpha 16 and CD34.

The hematopoiesis-specific G protein alpha subunit Galpha16 is a specific element in the signal transduction of the early hematopoietic cytokine network. As Galpha16 mRNA can be detected in early hematopoietic progenitor cells, RT-PCR for Galpha16 can be used as a sensitive marker of hematopoietic activity. The aim of this study was to test the possible use of Galpha16 determinations for monitoring cytokine effects on hematopoietic recovery after chemotherapy in patients. We correlated presence of Galpha16 mRNA and CD34 surface antigen with hematopoietic recovery in six lymphoma patients undergoing salvage therapy with different cytokine support (IEV followed by G-CSF, IL-3, or placebo). Regardless of different cytokine schedules with different time courses, hematopoietic recovery was always preceded by transcription of Galpha16. Monitoring the expression of Galpha16 mRNA by RT-PCR is a highly sensitive diagnostic tool for analyzing hematopoietic recovery after chemotherapy and for characterizing the effects of cytokines on hematopoiesis.

In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on G alpha16-positive hematopoiesis.

G proteins play an important role in signal transduction from cytokine receptors to intracellular effectors via different pathways, eg involving tyrosine kinases. In our previous studies, we demonstrated that mRNA expression of the hematopoiesis-specific G protein alpha-subunit G alpha16 is a sensitive marker indicating the appearance of early myeloid and lymphoid progenitors. This study was designed to investigate cytokine effects on hematopoiesis in vivo and in vitro as reflected by G alpha16 expression and sensitivity to the hemoregulatory peptide (pEEDCK)2 which harbors a structural homology to the effector domain of G alpha16. Investigations on blood samples from lymphoma patients undergoing salvage therapy with different cytokine support showed that monitoring of the expression of G alpha16 mRNA which appears to play a role in cytokine signalling via tyrosine kinases was a valuable complementation to CD34 screening for analyzing hematopoietic recovery after chemotherapy. We demonstrated that in contrast to CD34 which is only expressed in quiescent cells, G alpha16 transcription occurs independently of cell cycle state. In vitro, we could show that G alpha16 was also a valuable marker for confirming the immature state of ex vivo expanded blood stem cells from patients. A further part of the study was focused on the response of G alpha16 and CD34 expressing cells to the granulocyte-derived hemoregulatory peptide (pyroGlu-Glu-Asp-Cys-Lys)2 = (pEEDCK)2 which harbors a G alpha16-homologous sequence motif. Results obtained from in vitro assays which involved estimation of colony outgrowth from CD34-positive cells showed that the effect of (pEEDCK)2 on CD34 cells enhanced the effect of IL-3 or SCF. These data indicate that G alpha16 may co-operate with (pEEDCK)2 in triggering the cytokine response of immature hematopoietic cells.

Monitoring of hematopoietic recovery after autologous stem cell transplantation by analysis of G alpha 16 mRNA and CD34 surface glycoprotein.

The hematopoiesis-specific G protein alpha subunit G alpha16 was shown to be expressed in early normal and malignant hematopoietic cell lines and has been suggested to play an important role in signal transduction of hematopoiesis. We previously demonstrated a strict correlation of G alpha16 mRNA and CD34 antigen expression in peripheral blood stem cells (PBSC). In PBSC mobilization, both markers are detectable at the time of hematopoietic recovery and progenitor cell release. In this study the possible use of G alpha16 determination in peripheral blood samples for monitoring patients undergoing stem cell transplantation was investigated. Normal peripheral blood is negative for G alpha16 expression. In all five patients G alpha16 mRNA expression appeared shortly before the time of blood cell recovery. When tested together with CD34 (three cases) a pattern different from CD34 antigen expression was found, reflecting a different mechanism of action. In two cases with different time points of leukocyte and platelet recovery G alpha16 mRNA was detected at both time points but not in the interval, thus suggesting a role of G alpha16 in multipotent precursor cells. CD34 mRNA tested in three patients was not detected at any time; this argues for different regulation of CD34 and G alpha16 mRNA. G alpha16 may be used as an indicator of hematopoietic recovery after autologous stem cell transplantation, suggesting that there are cell type-specific G protein-mediated signal transduction pathways of early hematopoiesis.

Stimulation of the central and peripheral nervous system for the control of pain.

After suffering some setbacks since its introduction in 1967, stimulation of the spinal and peripheral nervous systems has undergone rapid development in the last ten years. Based on principles enunciated in the Gate Control Hypothesis that was published in 1968, stimulation-produced analgesia [SPA] has been subjected to intensive laboratory and clinical investigation. Historically, most new clinical ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm gives way to a reappraisal of the treatment or modality as side-effects or unanticipated problems arise. The last and third phase proceeds at a more measured pace as the treatment is refined by experience. This review is divided into three parts as it traces the progress of spinal cord stimulation [SCS] and peripheral nerve stimulation [PNS]. The review commences with a discussion of the theory of SCS and PNS, and is followed by early reports during which it became apparent that the modality is essentially only effective in the treatment of neuropathic pain. The last section describes the modern experience including efficacy in specific types of pain and concludes with recent accomplishments that dramatize the relief of pain which can be achieved in nonoperable peripheral vascular disease or myocardial ischemia. Over the years, a search for those transmitters that might be influenced by spinal cord stimulation focused on somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin and other amines, although only substance "P" was implicated. More recently, in animal studies, evidence that GABA-ergic systems are affected may explain the frequent successful suppression of allodynia that follows spinal cord stimulation. During the past eight years, much attention has been directed to studies that use a chronic neuropathic pain model. While PNS held significant promise as a pain relieving modality, early electrode systems and their surgical implantation yielded variable results due to evolving technical and surgical skills. These results dramatically reduced the continued development of PNS, which then gave way to a preoccupation with SCS. Modern development of SCS with outcome studies, particularly in relation to failed back surgery syndrome [FBSS] and the outcome of peripheral nerve surgery for chronic regional pain syndromes, has earned both modalities a place in the ongoing management of patients with intractable neuropathic pain. The last section, dealing with pain of peripheral vascular and myocardial ischemia, is perhaps one of the more exciting developments in stimulation produced analgesia and as the papers discussed demonstrate, can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. SCS and PNS has an important role to play in the management of conditions that are otherwise refractory to conservative or other conventional management.

Expression of G alpha 16, a G-protein alpha subunit specific for hematopoiesis in acute leukemia.

G-proteins are essential in signal transduction pathways. A G-protein alpha subunit termed G alpha 16 was found to be exclusively expressed in hematopoietic cell lines. In cells derived from patients, G alpha 16 expression has been detected in progenitor- and pre-B ALL cells and also in peripheral blood stem cells (PBSC). In this study, we analyzed G alpha 16 expression using a RT-PCR technique by testing elutriated blood cells from normal donors, PBSC from breast cancer patients and bone marrow or peripheral blood cells from acute leukemia patients. Both of two ALL patients and 15/16 AML patients expressed G alpha 16. In elutriation experiments, G alpha 16 expression was found in fractions containing the highest number of precursor cells but was absent in mature T and B cell fractions. In addition, CD34-enriched PBSC were positive for G alpha 16 expression. Further in vitro experiments using the cell line KG1 showed that G alpha 16 expression was not affected by the growth inhibiting hemoregulatory peptide pEEDCK which has a sequence homology present within G alpha 16. Taken together, these data demonstrate that G alpha 16 is expressed in various normal and malignant hematopietic progenitors but not in their differentiated counterparts. G alpha 16 could play a vital role in signal transduction pathways controlling proliferation in early normal and malignant hematopoiesis.

Analysis of peripheral blood progenitor cells demonstrates limitations of minimal residual disease diagnosis in a case of acute promyelocytic leukemia.

Detection of minimal residual disease (MRD) by analysis of the PML-RAR alpha fusion transcript using the RT-PCR method is routinely carried out on peripheral blood and bone marrow of patients with APL (AML, FAB:M3). Therapy aims to achieve repeated negative results in these patients thus confirming clinical complete remission. We report a case of APL in second complete remission in which no leukemic cells had been detected in BM and PB for 20 months, and in which PBPC-pheresis was carried out for future transplantation. In two of five pheresis PML-RAR alpha fusion transcripts were detected. This shows that the residual leukemic population may only reach detection level after enrichment by PBPC-pheresis.

B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment.

Human long-term bone marrow cultures (HLTBMCs) are a valuable in vitro model for studying the role of the haemopoietic microenvironment. Here we report the spontaneous appearance of EBV-positive B cells in 6/40 HLTBMCs from patients with various haematological diseases after 3-5 months of culture. After subcultivation of these cells, a novel type of cell line could be characterized, which displayed surface markers and morphological features typical for EBV transformed B-cell lines. As the deproteinized and ultrafiltrated culture supernatants of these cell lines were found to contain an agent with stroma toxic properties, they were termed SSB lines (stroma-toxic-agent-secreting B-cell lines). This agent also exhibited a colony-inhibitory activity on in vitro myelopoiesis and erythropoiesis. These properties are typical for the two polyamines spermine and spermidine which were detected at elevated levels in the culture supernatants of SSB lines. The hypothesis that latent presence of EBV in bone marrow may induce an increased synthesis of spermine and spermidine, which are known to be associated with malignant haematological diseases and bone marrow aplasia, is discussed.

Microscopic venous infiltration as predictor of relapse in renal cell carcinoma.

In a retrospective analysis at a single institution we evaluated the significance of various pathological phenomena on the disease-free survival of patients with radically resected renal cell carcinoma. Parameters considered were tumor extension (pT stage) according to the International Union Against Cancer, tumor invasion into the renal vein or vena cava (V stage), standard histological grading (G stage), nuclear grading (F stage) and microscopic venous infiltration. The pT stage had a significant impact on disease-free survival (p = 0.0004) of patients with radically resected tumors, as did G stage (p = 0.0001) and F stage (p = 0.002). In contrast to some previously reported results tumor extension to the renal vein and vena cava showed no influence on disease-free survival (p = 0.077). On the other hand, microscopic venous infiltration, defined as local tumor infiltration through all vessel structures including the endothelial layer leading to a free tumor extension into the vessel, had a significant impact on disease-free survival (p less than 0.0001). When stratifying either tumor size or nuclear differentiation against microscopic venous infiltration, the latter retained a superior influence on disease-free survival (p = 0.01 and p = 0.0079, respectively). We conclude that microscopic venous infiltration is the most important predictor of relapse in renal cell carcinoma.

[Vasovasostomy after vasectomy. The surgical results 1986-1989]. / Vasovasostomie nach Vasektomie. Operationsergebnisse 1986-1989.

The frequency of vasovasostomy has increased dramatically in recent years. A significant percentage of men who have previously undergone vasectomy are now seeking restoration of their fertility. The most common reason for requesting a reversal is remarriage. There were 90 bilateral vasovasostomies performed in 90 patients between 1986 and 1989. The procedure was done according to the technique described by Howards, in a single layer with 7 x 0 prolene and under fourfold magnification. The success rate was 87% for presence of spermatozoa in the ejaculate, 48% for pregnancy. The fertility rate decreases slowly with increasing interval between vasectomy and reanastomosis. These results are statistically significant. In cases of good anatomical and andrological conditions, the chance of restoration of fertility is good. The experience of the urologist is often more important than the details of the technique.

PIP: Vasectomy was performed in 500,000 men in the US in 1974, and 33 million couples chose this method of contraception worldwide according to a 1984 study. In 1987 there were about 25,000 vasectomies performed in West Germany. Subsequent desire to have a child necessitates vasovasostomy in numerous instances. Between 1986 and 1989, in a prospective study, a total of 90 men with average age of 39 years whose vasectomy had been performed at the average age of 32.1 years underwent bilateral vasovasostomies (VVST). The Howards method of anastomosis was used with prolene thread under fourfold magnification along with a spermiogram and a test of passability of the sperm duct. 64 patients were given a follow-up examination. The passability of anastomosis or spermatozoa in the ejaculate amounted to 87%. A postoperative spermiogram showed oligospermia in 84% (54 of 64) and a normal sperm count in only 2 cases. There were 8 cases of azoospermia owing to the closing of the anastomosis. A total of 31 pregnancies (48% rate) resulted in partners. The decrease of the pregnancy rate was statistically significant as the interval between vasectomy and VVST rose. Refertilization within 5 years after vasectomy produced a 63% pregnancy rate which was significantly higher than the 30% rate within 10 years. Beyond 10 years only an 8% pregnancy rate could be expected. The intraoperative sperm motility was not a good predictor of the expected pregnancy rate, as motility of sperm was found in only 38% and lack of motility in 55%. Laser VVST has been increasingly used, but its suitability has not been evaluated yet. The possible cause of the high rate of oligospermia is the resection during vasectomy of a nerve that controls sperm transport of the vas deferens. Thorough postoperative andrological and gynecological examination is needed for accurate assessment of the success or failure of the operation.