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Biomedical subjects

U Wesselmann

Publications and source records attributed to U Wesselmann.

At least 19 recordsLinked to original sources

History of the neurobiology of the pelvis.

The contemporary clinical management of a variety of pelvic disorders has benefited greatly from both basic science research discoveries and clinical observations in pelvic neurobiology. The foundation of this scientific discipline emanates from historical advances in the neuroanatomy and neurochemistry of the pelvic region. These advances, many of which were controversial when introduced, have served to shape currently accepted views regarding the neuroregulatory basis of pelvic functions. This report highlights the major contributions in the history of pelvic neurobiology, providing both an overview of the evolution of scientific thought in this discipline and insight into the role of this discipline in the development and practice of medicine and surgery related to the pelvic region.

Animals↗

Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180.

Lichen planus pemphigoides is an autoimmune subepidermal blistering disease. The finding of immunoglobulin G antibodies directed against the basement membrane zone differentiates it from bullous lichen planus. The aim of this study was to identify the target antigen of lichen planus pemphigoides autoantibodies. Sera from lichen planus pemphigoides patients (n = 4) stained the epidermal side of NaCl-split human skin in a pattern indistinguishable from that produced by bullous pemphigoid sera. In bullous pemphigoid, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. We previously demonstrated that bullous pemphigoid sera predominantly react with a set of four epitopes (MCW-0 through MCW-3) clustered within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, lichen planus pemphigoides sera were also strongly reactive with recombinant bullous pemphigoid 180 NC16A. The lichen planus pemphigoides epitopes were further mapped using a series of overlapping recombinant segments of the NC16A domain. All lichen planus pemphigoides sera reacted with amino acids 46-59 of domain NC16A, a protein segment that was previously shown to be unreactive with bullous pemphigoid sera. Two lichen planus pemphigoides sera, in addition, reacted with the immunodominant antigenic region associated with bullous pemphigoid. In conclusion, there are now five bullous diseases that are associated with an autoimmune response to BP180: bullous pemphigoid; pemphigoid/herpes gestationis; cicatricial pemphigoid; linear immunoglobulin A disease; and lichen planus pemphigoides. In addition, we have identified a novel epitope within the BP180 NC16A domain, designated MCW-4, that appears to be uniquely recognized by sera from patients with lichen planus pemphigoides.

Adult↗

Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma.

Spitz nevus is a benign neoplasm of melanocytes that can be difficult or impossible to distinguish from melanoma by clinical and histopathologic examination. We studied genomic DNA from 17 Spitz nevi by comparative genomic hybridization (CGH). Thirteen lesions showed no chromosomal aberrations, three cases had a gain involving the entire p-arm of chromosome 11, and one case showed a gain of chromosome 7q21-qter. Fluorescence in situ hybridization (FISH) on lesional tissue with a probe for the p-arm of chromosome 11 showed 6-10 p-arm signals per nucleus in those cases with a CGH-detected gain of chromosome 11p. One case with a normal CGH profile also showed increased copy number of 11p by FISH. Thus, the majority of Spitz nevi have a normal chromosomal complement at the level of CGH resolution; however some may contain gains, with 11p apparently being the most frequently involved location. These findings differ significantly from the previously reported changes in primary cutaneous melanoma, which show frequent deletions of chromosomes 9p (82%), 10q (63%), 6q (28%), and 8p (22%), as well as gains of chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%) by CGH analysis. These clear differences in the location and frequencies of chromosomal aberrations in Spitz nevi and primary cutaneous melanomas could represent a basis for developing adjunctive techniques for refining accuracy in the difficult differential diagnosis of spitzoid melanocytic neoplasms.

Adolescent↗

Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat.

We have developed a model of uterine inflammation in the rat. The purpose of this study was to characterize the behavioral manifestations of uterine pain. Mustard oil was injected into one uterine horn to produce chemical inflammation. Control rats were sham-operated. Non-stop videotape recording was performed for 7 days to monitor rat behavior. Rats with uterine inflammation showed abnormal behavior during the first 4 days (hunching, hump-backed position, licking of the lower abdomen, repeated waves of contraction of the ipsilateral oblique musculature with inward turning of the ipsilateral hindlimb, stretching, squashing of the lower abdomen against the floor) suggestive of visceral pain and evidence of flank muscle hyperalgesia over 7 days indicative of referred visceral pain. This model resembles closely a state of inflammatory uterine pain and will allow to gain further insight into the neural processes which contribute to visceral nociception.

Animals↗

Eosinophilic globules in spitz nevi: no evidence for apoptosis.

Eosinophilic globules are commonly found in Spitz nevi and can be of help in the differential diagnosis with melanoma. Despite their use as a diagnostic marker, there are conflicting concepts concerning the mechanism of the formation of these globules. Because pyknotic nuclei are often present in the cells surrounding the globules, many believe that apoptotic cell death of keratinocytes and melanocytes is an important mechanism in their formation. We studied nine Spitz nevi containing 21 eosinophilic globules for apoptotic cell death around and within Kamino bodies using the TUNEL method (TdT-mediated dUTP-x nick end-labeling method). In none of the cases were positive cells seen in the vicinity of the globules. Single apoptotic cells were found only sporadically in the melanocytes of the neoplasms (one to four per section) and were scattered throughout the entire lesion. The absence of apoptosis-specific labeled cells in the vicinity of eosinophilic globules and the rare occurrence of positive stained cells in other parts of the tumors makes apoptotic cell death unlikely to be relevant in the formation of eosinophilic globules.

Apoptosis↗

Paraneoplastic pemphigus treated with dexamethasone/ cyclophosphamide pulse therapy.

Paraneoplastic pemphigus (PNP) is an autoimmune, mucocutaneous bullous disease associated with underlying malignancies. We report a patient with Waldenström's macroglobulinemia who developed clinical, histological and immunopathological features typical of PNP. The patient was treated twice with i.v. dexamethasone and cyclophosphamide pulse therapy (day 1: cyclophosphamide 500 mg i.v.; day 1-3: dexamethasone 100 mg i.v.) at 3-week intervals. Therapy was continued with oral cyclophosphamide (50 mg/d). Two weeks after initiation of treatment, significant improvement of the cutaneous and mucosal lesions was noted. The therapy also had beneficial effects on the macroglobulinemia in terms of a marked reduction of the IgM lambda serum level. Three months after the second pulse, severe stomatitis recurred but the patient rejected any further systemic therapy. The initial response of the usually recalcitrant mucosal and skin lesions of PNP makes dexamethasone/cyclophosphamide pulse therapy an interesting therapeutic option.

Administration, Oral↗

[Pain syndromes in AIDS].

Pain is a major, but largely neglected problem in AIDS patients. The aim of this article is to review the etiology of pain manifestations in AIDS patients in different organ systems and to discuss appropriate treatment strategies. The most common pain symptoms in AIDS patients are headache, oral cavity pain, dysphagia and adynophagia, chest pain, abdominal pain and pain related to peripheral neuropathy. Symptomatic pain treatment should be started while diagnostic work-up is still in progress, so that the patient does not suffer. If etiological treatment is possible, specific treatment pain treatment tapered as tolerated. If etiological treatment is not possible, symptomatic pain treatment should be continued. In view of the multiple organs involved in the presentation of AIDS requiring multiple drugs, careful attention to side effects, contraindications and drug interactions is warranted, when administering pain medications. Fear of the complexity of these issues should, however, not prevent effective pain management for these patients, who suffer from a fatal disease. A multidisciplinary approach to pain in AIDS patients, similar to the approach in patients with cancer, is desirable.

Acquired Immunodeficiency Syndrome↗

The dynias.

The "dynias" are a group of chronic, focal pain syndromes with a predilection for the orocervical and urogenital regions. They include glossodynia, carotidynia, vulvodynia, orchidynia, prostatodynia, coccygodynia, and proctodynia. In some cases, the dynias occur secondarily, but more often, despite an exhaustive evaluation, no etiology is found and in these remaining cases, the cause of the pain remains enigmatic. The controversy that surrounds this group of disorders, which ranges from questioning their existence to suggesting that they are purely psychosomatic, is counterbalanced by an extensive literature attesting to their organicity. The approach to the patient begins with acknowledging that the symptom is well described, searching for a secondary cause, and performing a careful psychologic assessment. Treatment is empirical and patients can often be helped with medications used to treat neuropathic pain, all the while providing psychologic support and exercising caution toward invasive and irreversible therapeutic procedures.

Adult↗

Galactorrhea and hyperprolactinemia in schizophrenic patients on neuroleptics: frequency and etiology.

The frequency of galactorrhea and the subjective response to it were investigated in 150 schizophrenic patients. The incidence rate was 14% and the prevalence rate 19%. The latency periods between start of neuroleptic medication and manifestation of galactorrhea were subject to substantial scatter, as were the prolactin values. Patients who had undergone neuroleptic relapse prevention prior to the index episode and/or had been pregnant were affected significantly more frequently by galactorrhea.

Adult↗

Galactorrhea: subjective response by schizophrenic patients.

The frequency of galactorrhea and the subjective response to it were investigated in 150 schizophrenic patients. The incidence rate was 14% and the prevalence rate 19%. More than half the women experienced galactorrhea in connection with their femininity, with this side effect of neuroleptic therapy being rated more often as a positive effect, especially as a reinforcement of feminine identity or as an expression of the ability to conceive children. The overall response to galactorrhea was positive among 43% and negative among 20%, with the remaining patients tending towards indifference.

Adaptation, Psychological↗

Laser effects on myelinated and nonmyelinated fibers in the rat peroneal nerve: a quantitative ultrastructural analysis.

We have recently shown that Nd:YAG laser irradiation of rat peripheral nerve differentially impairs action potential transmission in small, slowly conducting sensory fibers compared to fast conducting afferents. In addition, the number of small sensory neurons of the A-delta- and C-fiber group labeled with HRP is significantly reduced after laser irradiation, while the number of labeled large sensory neurons and motoneurons was not affected. To further evaluate this laser-induced injury, we examined three distinct regions of the laser-irradiated rat peroneal nerve using ultrastructural morphometric methods. These regions were the site of laser irradiation and zones 10 mm proximal and 5 mm distal to the injury. The contralateral nerve was sham treated. Our results indicate that for the small nonmyelinated fibers, there was a significant increase in both mean fiber size and the number of microtubules per fiber, but a decrease in the number of neurofilaments. In contrast, the number of myelinated and nonmyelinated fibers is not significantly altered at 7 days following laser irradiation, and the mean diameter and frequency distribution of myelinated nerve fibers was unchanged. This study demonstrates that selective functional alterations in laser-irradiated nerves (nerve conduction velocity, HRP transport properties) are accompanied by ultrastructural changes of axonal organelles in nonmyelinated fibers. Nd:YAG laser light might ultimately prove to be a powerful tool to selectively alter functional properties in small, slowly conducting afferent fibers, without causing degeneration at the ultrastructural level at the site of irradiation. We hypothesize further that the laser-induced functional alterations might be related to differential thermally mediated changes.

Animals↗

Retrograde horseradish peroxidase transport in motor axons after Nd:YAG laser irradiation of the tibial nerve in rats.

We have recently demonstrated that the number of small sensory neurons of the A-delta- and C-fiber group in lumbar dorsal root ganglia labeled with horseradish peroxidase (HRP) is selectively decreased 7 days after Nd:YAG laser irradiation of the tibial nerve in the rat. In contrast, the number of large diameter sensory neurons was not affected by laser application. In an attempt to clarify the fate of motoneurons after laser irradiation of their peripheral axons, the numbers of lumbar motoneurons retrogradely labeled with HRP 7 days after Nd:YAG laser irradiation of the tibial nerve have been determined in rats. Our results show that the number of HRP-labeled motoneurons in lumbar segments L6 to L3 is not altered to a significant extent after laser irradiation of their peripheral axons (laser-treated side, 767 +/- 10 cells vs control side, 808 +/- 19; n = 5, mean +/- SEM). In addition, no difference was detected in the mean value or the distribution of soma cross-sectional areas of labeled motoneurons on the laser-treated side and the control side. Specifically, the numbers of HRP-labeled small diameter motoneurons, which are presumably gamma in type and have a conduction velocity similar to sensory neurons of the A-delta group, were not affected by laser application. Possible mechanisms of the differential vulnerability of sensory neurons as compared to motoneurons of similar size are discussed.

Animals↗

Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in the rat.

Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.

Animals↗

Differentiation of sympathetic neurones projecting in the hypogastric nerves in terms of their discharge patterns in cats.

1. Sympathetic neurones that project in the hypogastric nerves (HGNs) were analysed for their discharge patterns in anaesthetized cats. The activity of these neurones was recorded from their axons. Afferents from the pelvic organs (urinary bladder, colon, anal canal), and arterial baro-and chemoreceptors were stimulated. 150 postganglionic and nine preganglionic neurones were analysed. 2. The postganglionic neurones exhibited reflex patterns that were typical of visceral vasoconstrictor neurones and various types of motility-regulating neurones. Most motility-regulating neurones and all visceral vasoconstrictor neurones had ongoing activity. 3. Postganglionic motility-regulating neurones were not influenced by stimulation of arterial baro-and chemoreceptors, but showed distinctive reflexes on stimulation of afferents from pelvic organs. Three subgroups of motility-regulating neurones were identified: type 1 neurones (34% of the sample of postganglionic neurones) were excited from the urinary bladder and inhibited or not influenced from the colon. Type 2 neurones (14%) exhibited a reflex pattern reciprocal to that of the type 1 neurones. Anal motility-regulating neurones (8%) were only influenced from the anal canal. The most powerful reflexes in these types of motility-regulating neurones were elicited by mechanical stimulation of the anal mucosa. 4. Postganglionic visceral vasoconstrictor neurones (16% of the sample) were under powerful inhibitory control from the arterial baroreceptors and weakly excited by stimulation of arterial chemoreceptors. Visceral stimuli had little or no effect on most of these neurones. Some visceral vasoconstrictor neurones exhibited some overlap in their functional properties with motility-regulating neurones. 5. Twenty-eight per cent of our sample of postganglionic neurones showed no reflexes to the afferent stimuli used. About half of these neurones had on-going activity. 6. Nine preganglionic neurones with on-going activity were identified. Most of these neurones behaved like visceral vasoconstrictor or motility-regulating neurones. 7. This study shows that the majority of postganglionic neurones that project in the HGNs can be divided into the same functional types as the lumbar preganglionic neurones that project to the inferior mesenteric ganglion. The proportions of the different types of neurones are similar at pre- and postganglionic levels. Thus the centrally generated patterns of activity are most likely faithfully transmitted from the spinal cord to the target organs in the pelvic cavity in functionally separate pathways.

Anal Canal↗

Effects of muscle fatigue on mechanically sensitive afferents of slow conduction velocity in the cat triceps surae.

1. Group III and IV muscle afferents have been shown to be sensitive to both mechanical stimuli and metabolic and thermal changes in muscle. To establish the potential role of slowly conducting muscle afferents in regulating motor output during fatigue, we recorded from mechanically sensitive group III and nonspindle group II afferents originating in the triceps surae in barbiturate-anesthetized cats. We evaluated the response of these afferents to tetanic muscle contraction, stretch, and surface pressure, before, during, and after fatigue. 2. Our results show that muscle fatigue both increases spontaneous discharge in these mechanically sensitive afferents and sensitizes their response to muscle stretch, surface pressure, and, in a few instances, muscle contraction. These fatigue-induced changes typically occurred after 5-10 min of submaximal fatiguing stimulation. 3. During recovery from muscle fatigue, several contraction-sensitive free nerve endings, which had become sensitized to contractions during fatigue, remained sensitized after 20-30 min of rest. 4. The results of this study provide support for the hypothesis that fatigue-induced excitation of slowly conducting afferents is significant in mediating fatigue-induced inhibition of motoneuron output. However, our finding that the discharge of many slowly conducting mechanoreceptor afferents declines during the initial phase of fatigue argues against a primary role for these afferents in mediating the initial decline in motoneuron rate that is so prominent in fatiguing maximum voluntary muscular contraction.

Afferent Pathways↗

Effects of Q-switched Nd:YAG laser irradiation on neural impulse propagation: I. Spinal cord.

We studied the effect of irradiation with Q-switched Nd:YAG laser light (1064 nm) on spinal cord dorsal column and dorsolateral white matter in anesthetized rats. To evoke a synchronous sensory input, the sciatic nerve was stimulated electrically and the resulting evoked spinal cord potential (SCP) recorded from the dorsal columns of the ipsilateral side. The waveshape of the SCP showed three components: an early positive peak (P1), representing the responses of the most rapidly conducting fibers, followed by two negative peaks (N1 and N2), which are mainly due to synaptic effects of the volley on dorsal horn cells located in dorsal grey matter. Laser irradiation at 50 mJ/pulse and above resulted in severe reduction in the amplitudes of N1 and N2. In contrast, there was either no reduction at all or only a slight decrease in the amplitude of P1. The selective loss of the synaptic field might be mediated by impairment of synaptic transmission or by loss of high threshold fiber input to dorsal horn neurones. In either event it is likely that the mechanism of the differential effects of laser irradiation on the components of the electrically evoked SCP is at least in part photothermally mediated, since intracord temperatures during laser application greatly exceeded the physiological range.

Animals↗

Effects of Q-switched Nd:YAG laser irradiation on neural impulse propagation: II. Dorsal roots and peripheral nerves.

We have studied the effects of Q-switched Nd:YAG laser irradiation on transmission of neural impulses in sensory nerve fibers in anesthetized rats and cats. Laser light was applied to dorsal roots (rat, cat) and to the sciatic nerve (rat) at increasing pulse energies ranging from 10 to 100 mJ/pulse for 5 minutes each. Compound action potentials recorded from dorsal roots and the sciatic nerve in response to high intensity electrical stimulation during laser application at increasing pulse energies showed a progressive preferential reduction of the slow late component of the electrically evoked response. Preliminary data from multifilament recordings from dorsal roots in cats demonstrated that conduction in small slow conducting fibers was blocked at lower laser pulse energies than in fibers with faster conduction velocities. These results imply, that laser light might have differential effects on slow versus fast conducting sensory nerve fibers. It is most likely that the preferential effect of laser irradiation on slow conducting fibers is mediated by photothermal mechanisms, since temperature increased substantially during laser application.

Action Potentials↗