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Biomedical subjects

U Jonas

Publications and source records attributed to U Jonas.

At least 19 recordsLinked to original sources

The influence of anterior root stimulation (S2) in deafferented spinal cord injury men on cavernous electrical activity.

Registration of cavernous electrical activity (single potential analysis of cavernous electrical activity) was recently suggested for the diagnosis of autonomic cavernous dysfunction. For validation of this method the effect of sacral neurostimulation on cavernous electrical activity was examined. In 3 male patients with a complete spinal cord lesion (T3, T4 and T12, respectively), deafferentation was done at the S2 to S5 levels. Around the anterior roots of S2 to S5 electrodes for neurostimulation were placed. Cavernous electrical activity was recorded with an intracavernous needle electrode and with surface electrodes in the flaccid as well as in the erect states induced by neurostimulation (at 7, 8, 12, 18, 20, 30 and 45 Hz., 30 v. and 0.4 msec). In all patients similar potentials compared to the normal values, as well as additional pathological potentials were recorded during flaccidity. During neurostimulation all patients achieved full erection with no or markedly decreased cavernous electrical activity to frequencies of 12, 18, 20 and 30 Hz., while to 7, 8 and, more pronounced, 45 Hz. only partial erection with ongoing cavernous electrical activity was found. Our study strongly suggests that cavernous electrical activity and, subsequently, the cavernous smooth muscle tone are dependent on autonomic input. This finding supports the hypothesis that single potential analysis of cavernous electrical activity may be valid in the diagnosis of cavernous autonomic dysfunction. Furthermore, our results suggest a possible role for single potential analysis of cavernous electrical activity in the fine tuning of erection inducing neurostimulators.

Adult

A new therapeutic concept for long-lasting iatrogenic priapism: a case report.

In a therapeutic attempt on an 18-year-old patient with iatrogenic priapism lasting for more than 2 weeks after internal urethrotomy, intracavernous lysis was commenced with 80,000 IU streptokinase per hour. Following a dosage of 300,000 IU streptokinase the lysis was stopped because of severe bleeding from the urethrotomy scar. At 4 weeks after the patient was discharged from the hospital he reported normal erections and intercourse, while single potential analysis of cavernous electrical activity and ultrasound returned to normal. Provided there are no contraindications, intracavernous lysis seems to be an effective treatment for long-lasting priapism induced by intracavernous thrombosis.

Adolescent

Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction.

Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitric oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. SIN-1 were injected intracavernously in patients with erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. SIN-1, including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond with a full erection to other pharmacological agents. Intracavernous injection of SIN-1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a full, 21 an almost full and 13 a moderate erection to 1 mg. SIN-1. There were no systemic or local side effects. In the patients with prolonged erections to papaverine plus phentolamine the mean duration of a full erectile response to SIN-1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by SIN-1 was superior in 10, comparable in 47 and inferior in 6 patients. Our data suggest a possible role for SIN-1 in the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs.

Blood Flow Velocity

Significant obliteration of the urethral lumen after Wallstent implantation.

The permanently implanted self-expandable urethral stent (Wallstent) has found increased use in patients with recurrent urethral strictures because of its simple implantation technique. To date there have been no reports of serious complications. At 6 weeks after stent implantation our patient had complete luminal obstruction. This complication demonstrates the need for short-term controls after implantation of a urethral stent.

Aged

Transcutaneous registration of cavernous smooth muscle electrical activity: noninvasive diagnosis of neurogenic autonomic impotence.

Registration of cavernous electrical activity was shown to be a possible method for the evaluation of cavernous autonomic innervation. Recent studies in patients with normal erectile function showed that cavernous electrical activity is synchronous throughout the entire cavernous bodies. Therefore, we examined the feasibility of transcutaneous registration of cavernous electrical activity in 8 normal and 62 impotent patients. In the sitting patient cavernous electrical activity was recorded with a 2-channel electrophysiological unit. Recording was done with a coaxial needle electrode in the proximal left cavernous body and with surface electrodes bilaterally on the penile shaft. In 7 of 8 normal patients swelling of the penile shaft after circumcision resulted in a dramatically decreased amplitude of the potentials. In 41 of 62 impotent patients recordings were similar. In 10 of 62 patients no recording or markedly decreased amplitudes were noted with the surface electrodes and in these patients a small penis or penile retraction with consecutive electrode displacement was found. Careful repositioning of the surface electrodes with the patient in the supine position resulted in similar recordings in 9 (inconsistently in 4). In 11 of the 62 patients more information was obtained with the surface than with the needle electrode. Our results show that recording of cavernous electrical activity can be done in a completely noninvasive manner using surface electrodes with similar or even better information obtained than with needle electrodes.

Action Potentials

Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients.

We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry for the presence of protease inhibitors. Immunoreactivity for alpha 2-macroglobulin (alpha 2-M), the most potent of the known human protease inhibitors, was found in a subgroup of cortical and hippocampal AD senile plaques. In addition, large hippocampal neurons in AD brains displayed intracellular alpha 2-M immunoreactivity which was consistently stronger than in normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M behaves as an acute-phase protein in the nervous system. Therefore, we also examined AD brains for the presence of IL-6 and found strong immunostaining in and around a subgroup of senile plaques as well as around large cortical neurons. Only very few senile plaques also stained for C-reactive protein, an acute phase protein known to be inducible by IL-6. We propose that the presence of IL-6 and alpha 2-M immunoreactivity in AD brains is functionally linked and that a sequence of immunological events is part of the pathology of AD.

Aged

Treatment of anejaculation with electroejaculation.

Male infertility caused by anejaculation is common after spinal cord injury (SCI) and following retroperitoneal lymph node dissection (RPLND) for testicular cancer. Other conditions sometimes associated with neurogenic ejaculation loss are diabetes mellitus, multiple sclerosis, extensive pelvic surgery and adult myelodysplasia. Primary absence of ejaculation also has been described. Few treatment options exist for these patients, if they wish to father a child. With electroejaculation (EEJ), or the low-current stimulation of the ejaculatory organs via a rectal probe, emission of semen can be initiated in these men. In non-SCI-patients EEJ requires general anaesthesia. The collected semen is washed and the motile sperm fraction isolated before artificial insemination (AI) of the partner. At the University of Michigan 198 men have been treated between 1986 and December 1991. An ejaculate could be obtained from nearly all patients. A major obstacle to success is the severe asthenozoospermia and the poor functional quality of the obtained sperm samples. This can be caused by the EEJ-technique itself, as well as by the long anejaculatory status. A semen sample with at least 10 million progressively motile sperm cells, useful for AI, was obtained in 75% of the SCI men and in 87% of the men following RPLND. In the couples wishing insemination, 49 pregnancies were induced, accounting for an overall pregnancy rate of 35% per couple. Thirty five healthy babies have been born. Only three complications were encountered. At Hannover Medical School only few patients have been stimulated to date. We could obtain an adequate sperm sample for AI from all of them. No complications were seen. As the first couple has just entered the phase of AI with husband sperm, an analysis of these results would be premature. Electroejaculation combined with artificial insemination is an efficient and safe treatment of male infertility due to neurogenic anejaculation.

Adult

[ESWL in hemophilia B].

One of the most dramatic dangers in treating nephrolithiasis by ESWL is the development of intra- and perirenal bleeding, which requires therapeutic intervention. Even in patients whose blood parameters suggest they are healthy, hematomas are found in up to 80%. Therefore, ESWL must be regarded as contraindicated in patients with blood disorders. A case of a patient suffering from hemophilia B and from a large renal pelvic stone is reported, whom we treated by ESWL twice after sufficient substitution. X-ray revealed that the patient was stone-free on the 25th day after the first ESWL session. ESWL. A review of the literature is presented.

Adult

[Vasectomy: minor intervention--grave sequelae].

Claims for compensation following dissatisfaction with the results of medical treatment have increased in frequency over the last few years. Medical records, such as declarations of consent and operation reports, often constitute important evidence in legal proceedings, particularly in the field of surgery. Before a vasectomy is performed for the purpose of contraception, detailed information must be given on how safe this is as a method of birth control and the patient must be made aware of the importance of sperm count controls after the operation. The surgeon is held responsible if it can be shown that a failed sterilization is due to ligation of only one vas deferens or to failure to notice an accessory one. Claims for compensation can include support for children up to the age of 18 years and financial compensation to the mother in respect of the labour pains.

Humans

In-vitro matured human macrophages express Alzheimer's beta A4-amyloid precursor protein indicating synthesis in microglial cells.

Microglia which are consistently associated with Alzheimer's disease (AD) senile plaques are part of the mononuclear phagocyte system. In-vitro matured human monocyte-derived macrophages feature many immunological characteristics of microglia. We found strong constitutive expression of Alzheimer's beta A4-amyloid precursor protein (APP) in human mononuclear phagocytes after terminal in-vitro maturation from monocytes to macrophages. Amyloid has previously been found to be associated with microglia in AD brains, however, it remained unclear whether the material was synthesized in or had been phagocytosed by the cells. The findings presented here support the assumption that brain microglia may contribute to APP synthesis in AD brain.

Amyloid beta-Peptides

Alpha 2-macroglobulin synthesis in interleukin-6-stimulated human neuronal (SH-SY5Y neuroblastoma) cells. Potential significance for the processing of Alzheimer beta-amyloid precursor protein.

Cultured human neuronal (SH-SY5Y neuroblastoma) cells synthesize and secrete the potent protease inhibitor alpha 2-macroglobulin (a2M) upon stimulation with interleukin-6 (IL-6) indicating that alpha 2-macroglobulin behaves as an acute-phase protein in the human central nervous system. Exogenous addition of a2M to the cultured neuronal cells resulted in only a slight inhibition of Alzheimer beta A4-amyloid precursor protein (APP) synthesis, but markedly inhibited its secretion pointing to the possibility that a2M may affect the proteolytic APP processing. Evidence is provided that IL-6 and a2M are involved in Alzheimer's disease pathogenesis.

Alzheimer Disease

Single potential analysis of cavernous electrical activity.

Recording of cavernous electric activity was performed in 178 patients with erectile dysfunction and in 37 normal patients. In 34/37 normal patients, potentials of a uniform shape were recorded during flaccidity: At cut-off frequencies of 0.5-500 Hz, the length was 8-18 (mean 12.8, SD 2.8), the amplitude 250-750 (mean 444, SD 109) microV, and the polyphasity 8-22 (mean 13.8, SD 3.3). In impotent patients with upper motor neuron lesions or peripheral lesions, specific types of potentials were observed. In 11/14 impotent patients with insulin-dependent diabetes for over 20 years and clinical findings of cavernous myopathy, potentials showed low amplitude, irregular shape, and slow depolarizations. In 51% of the consecutive impotent patients, abnormal findings of cavernous electric activity were recorded. Our clinical study suggests that single potential analysis of cavernous electric activity (SPACE) may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.

Action Potentials

In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a.

Samples of 38 human renal cell carcinomas (RCC) were subjected to routine histopathological examination but also to in vitro sensitivity testing with mitomycin C, vinblastine and interferon Alpha-2a at various concentrations corresponding to serum titers recommended to be effective in vivo, employing a monolayer assay. Extending earlier in vitro studies, both tumor cell kill rates (TCKR) and proliferation rates (PR) were assessed. Following in vitro preparation the tumor cell cultures were simultaneously exposed to the anticancer drugs listed above. The proliferation rates were determined immunocytochemically using the monoclonal antibody Ki-67. Nine (23.7%) of the tumors investigated revealed temporary and limited response with respect to either TCKR or PR. Improvement of this percentage could only be obtained by increasing drug concentration to titers with toxicity intolerable for in vivo administration. The in vivo data presented correspond to clinical temporary and limited remissions in patients with metastatic RCC ranging up to 25%.

Antineoplastic Combined Chemotherapy Protocols

Metastatic renal cell carcinoma (RCC): spontaneous regression, long-term survival and late recurrence.

We report 4 cases of metastatic renal cell carcinoma (RCC) with long-term survival either following radical nephrectomy alone or in combination with radio- or hormonal therapy. Two patients with lymph node metastases showed a long-term survival of 12 or more years following radical tumour nephrectomy (with lymphadenectomy) and radiotherapy. One of them exhibited a histologically proven tumour recurrence nearly 12 years after primary surgical treatment and died shortly later; the other one is still without any evidence of metastatic disease. Two other patients exhibited spontaneous regression of pulmonary metastases: one regression occurred after radical tumour nephrectomy alone, the other one after successful primary hormonal treatment and subsequent radical tumour nephrectomy. The following important aspects are emphasized: 1. Renal cell carcinoma is a very unpredictable tumour. Once the diagnosis of renal cell carcinoma is proved, a patient can never be considered cured. 2. Although adjuvant palliative nephrectomy has produced contradictory results in several reports, radical tumour nephrectomy either alone or in combination with other adjuvant therapies such as radiotherapy, hormonal or immunological treatment, can be worthwhile. Cases with long-term survival and spontaneous regression of distant metastases are proof of this. Besides, if carefully selected, the mortality rate of different adjuvant therapies is not significantly higher in patients with metastatic disease than in patients without metastases. The world literature on this subject is reviewed.

Aged

Single potential analysis of cavernous electrical activity in impotent patients: a possible diagnostic method for autonomic cavernous dysfunction and cavernous smooth muscle degeneration.

Cavernous electrical activity was recorded in 214 patients with erectile dysfunction and in 39 normal patients. In 34 of the 39 normal patients potentials of a uniform shape were recorded during flaccidity. At cutoff frequencies of 0.5 to 500 Hz. the duration was 8 to 18 seconds (mean 12.8 +/- 2.8, seconds, standard deviation), the amplitude was 250 to 750 microv. (mean 444 +/- 109 microv.) and the polyphasity was 8 to 22 (mean 13.8 +/- 3.3). With increasing tumescence and rigidity during audiovisual sexual stimulation, high frequency potentials of low amplitude and short duration were found in the normal patients. In impotent patients with an upper motor neuron or peripheral lesion specific types of potentials were observed. In 11 of 14 impotent patients with insulin-dependent diabetes for more than 20 years and with clinical findings of cavernous myopathy the potentials showed low amplitude, irregular shape and slow depolarizations. Abnormal findings of cavernous electrical activity were recorded in 51.6% of the consecutive impotent patients. Our clinical study suggests that single potential analysis of cavernous electrical activity may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.

Adult

Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients.

A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5 ng. (2 patients), 50 ng. (2 patients), 500 ng. (4 patients), 5 micrograms (4 patients) and 25 micrograms (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin-gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine. Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin-gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500 ng. to 25 micrograms. Systemic side effects were first observed at a dose of 25 micrograms in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin-gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene-related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence.

Adult

Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit.

Using a rabbit model, the involvement of the L-arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4-8 V, 20-30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of: (1) the slope of the initial, ascending part of the pressure increase; (2) delta P, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of delta P. Intrapenile administration of the L-arginine/nitric oxide synthesis inhibitor NG-nitro-L-arginine had no effect on systemic arterial blood pressure. However, NG-nitro-L-arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and delta P decreased significantly. NG-nitro-D-arginine (2.19), on the other hand, had no inhibitory effect. L-arginine (21.07 mg), given either directly or after NG-nitro-L-arginine had no consistent effect on the functional response to cavernous nerve stimulation. The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively, and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG-nitro-L-arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.

Amino Acid Oxidoreductases