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Biomedical subjects

P Frey

Publications and source records attributed to P Frey.

At least 73 records · Page 4Linked to original sources

Immunohistochemical study of cholecystokinin peptide in rat spinal motoneurons.

With the aid of indirect immunofluorescence histochemistry and sequence specific antibodies a possible localization of cholecystokinin (CCK) peptide in spinal motoneurons has been analyzed. To increase peptide levels, the sciatic nerve was ligated, and the area around the ligation was studied 24 hours later. For comparison, antisera raised against calcitonin gene-related peptide (CGRP) and substance P were employed. With CCK specific antisera (directed to the N-terminal portion of CCK-8 or the midportion of CCK-33) accumulation of peptide-like immunoreactivity (LI) was observed in large, dilated axonal swellings proximal to, but at some distance from, the ligature. Such accumulations were also observed with C-terminally directed CCK antiserum, but in addition numerous axons of smaller diameter extending up to the ligation contained this type of immunoreactivity. The latter antiserum is thought to cross-react with CGRP. In fact, this staining pattern was indistinguishable from the one seen after incubation with CGRP antiserum. In contrast substance P-LI could not be seen in the larger dilated axons but only in large numbers of thinner fibers close to the ligation. Double staining experiments revealed that the large dilations contained both CGRP- and CCK-specific LI. Distal to the ligation CGRP- and substance P- but no specific CCK-LI could be observed. The present findings support the view that CCK mRNA in spinal motoneurons is translated into CCK peptide, at least after axotomy, and that the peptide is transported into the motoneuron axon. However, compared to CGRP the CCK levels are presumably low, and the functional role of CCK peptide in motoneurons remains to be established.

Animals↗

Testicular tumours in infancy and childhood--a review of 10 germ cell tumours and 10 non germ cell tumours.

Between 1961 and 1989 twenty testicular tumours were treated at the Basel University Children's Hospital. Ten were non germ cell tumours (50%) and a further 10 (50%) were germ cell tumours. Of the germ cell tumours six were benign teratomas, two yolk sac tumours and a further two were teratocarcinomas. In the non germ cell group eight tumours originated from paratesticular structures, one of which was a malignant rhabdomyosarcoma. The remaining two neoplasms originated from the supporting testicular tissues. The clinical presentation, the protocol of treatment and the long-term outcome are discussed. We advocate local tumour excision in benign cases (proven by instant frozen section) if normal testicular tissue can be preserved. In malignant germ cell tumours primary orchiectomy and high spermatic cord ligation is the treatment of choice. Secondary chemotherapy and/or retroperitoneal lymph node dissection is only added if the tumour markers alpha-fetoprotein and beta-human chorionic gonadotropin remain present in high serum levels postoperatively. Rhabdomyosarcomas are treated by surgical excision, primary chemotherapy and radiotherapy. All of the five patients (25%) suffering from malignant testicular tumours survived. A long-term follow-up (mean 12 years) did not show any evidence of recurrent local or metastatic disease.

Adolescent↗

Growth disturbance following metaphyseal bending fractures of the proximal tibia--an experimental study in the mini pig.

Based on our clinical experience, we postulate that the unilateral "posttraumatic genu valgum" develops on the grounds of an unreduced primary valgus deformity. This induces a disturbance of the consolidation on the medial aspect of the fracture. Subsequently, a partial medial stimulation of the epiphyseal plate develops resulting in a secondary valgus deformity. We succeeded in proving experimentally this postulate using the Mini Pig as an experimental model. We investigated 33 tibiae of 17 Mini Pigs. With radiological follow-up studies we were able to show that the operatively created primary valgus deformity induces an increased valgus deformity of functional significance. This is a model of the unreduced fracture in men. However, the transection of the pes anserinus and the periost per se did not provoke a significant valgus formation. Based on these experimental results and our clinical findings we postulate the following treatment for the metaphyseal bending fractures of the proximal tibia in men: 1. Accurate, usually conservative, reduction of any primary valgus malposition of the fracture. 2. Retention of the corrected position of the tibia in a plaster cast. 3. Compression of the medial aspect of the fracture to prevent disturbance of consolidation and subsequent development of valgus deformity.

Animals↗

[The transformation of Basedow's struma into nodular goiter: a reason for recurrence of hyperthyroidism].

Graves' disease is characterized by a diffuse and homogeneously hyperfunctioning goiter, presumably caused by thyroid stimulating, TSH-receptor directed antibodies (TRAB). However, in many patients the serum concentration of TRAB is in no way parallel to the severity of the clinical course of Graves' hyperthyroidism. In particular, hyperthyroidism may persist or repeatedly relapse over many years despite the absence of high TRAB titers. The present study summarizes the existing evidence that this course of Graves' disease may be due to gradually evolving autonomously growing and functioning micro- or macronodules within the originally diffuse goiter.

Adult↗

Microvascular autotransplantation of intra-abdominal testes.

In the period between 1981 and 1987, 23 microvascular autotransplantations of intra-abdominal testes were performed on 18 patients at the Royal Manchester Children's Hospital. Nineteen testes [82.6%] were successfully revascularised; however, four [17.4%] became partially or totally atrophic. Early surgery is recommended--well before the age of 2 years, prior to the onset of testicular damage, in order to reduce the risk of infertility. Although the early results are very encouraging, only long-term, postpuberty follow-up regarding both fertility and malignancy can determine the value of testicular autotransplantation.

Abdomen↗

One-stage preputial pedicle flap repair for hypospadias: experience with 100 patients.

Between 1980 and 1986, 224 patients underwent one-stage hypospadias repair, of whom 100 were operated on using a modification of the Asopa technique. This technique, in which a vascularised preputial pedicle flap is rotated ventrally in order to reconstruct a neo-urethra as well as to cover the ventral skin defect, is described. The post-operative results are discussed. Fistula formation was the most common complication, but was easily correctable.

Humans↗

Reconstruction of foreskin in distal hypospadias repair.

In the period between 1980 and 1985 101 one-stage repairs for distal hypospadias were carried out. Fifty-five patients were operated on using the Magpi technique as originally described by Duckett (1981). The hypospadias of the remaining 46 patients were corrected using a modification of this technique incorporating reconstruction of the foreskin. The technique of the modified, prepuce-preserving operation is described. Despite complications such as moderate meatal stenosis, fistulae and glandular-meatal as well as foreskin dehiscence, the overall functional and cosmetic results were very good.

Humans↗

Anterior pelvic osteotomy. A new operative technique facilitating primary bladder exstrophy closure.

Posterior iliac osteotomy is a recognised method employed to facilitate and support anterior abdominal wall closure in patients with bladder exstrophy, but it adds considerably to the already lengthy procedure of bladder exstrophy surgery. Anterior pelvic osteotomy of the superior ramus of the pubic bone was developed to overcome this problem and to achieve a stable anterior pelvic ring with tension-free soft tissue closure. It can easily be performed after completing the bladder closure, without the need to turn the patient.

Bladder Exstrophy↗

6,7-Dichloro-3-hydroxy-2-quinoxalinecarboxylic acid is a relatively potent antagonist at NMDA and kainate receptors.

The 6,7-dichloro derivative of 3-hydroxy-2-quinoxalinecarboxylic acid (diCl-HQC) is a relatively potent antagonist at the two excitatory amino acid receptor subtypes activated by N-methyl-D-aspartate (NMDA) and kainic acid. It antagonizes NMDA-induced excitation in the frog spinal cord (pA2 5.8), i.e. with a potency similar to D-2-amino-7-phosphonoheptanoate (D-AP-7). It also antagonizes NMDA-induced sodium efflux from rat brain slices (pA2 5.6). The compound inhibits kainic acid-induced sodium efflux from rat brain slices with a pA2 of 5.4 and it inhibits [3H]kainic acid binding to rat brain membranes with a pKi of 5.4. DiCl-HQC is only weakly active at the quisqualate receptor. This spectrum of activities may make this compound a useful tool to investigate the pharmacology of excitatory amino acid receptors.

Animals↗

A subpopulation of dopaminergic neurons in rat ventral mesencephalon contains both neurotensin and cholecystokinin.

The coexistence of the neuropeptides neurotensin and cholecystokinin and the catecholamine-synthesizing enzyme tyrosine hydroxylase within neurons of the ventral mesencephalon was analyzed using an immunofluorescence triple-labeling technique. Virtually all of the neurotensin-positive cell bodies in the ventral tegmental area, medial substantia nigra pars compacta, retrorubral field, and rostral and caudal linear raphe nuclei were found to contain both cholecystokinin and tyrosine hydroxylase immunoreactivities. The degree of colocalization was lower and more variable in other regions including the ventral and central periaqueductal grey matter and dorsal raphe nucleus. It appeared that immunoreactivities for these 3 neuroactive substances were not contained within the same axonal-like fibers and terminals in the ventral midbrain. These results demonstrate that a subpopulation of dopaminergic neurons, which presumably comprise part of the ascending mesotelencephalic system, contains the two peptides neurotensin and cholecystokinin. Thus, the data suggest a morphological basis for some of the reported functional interactions of these 3 putative neurotransmitters/neuromodulators within this system.

Animals↗

Immunohistochemical studies of cholecystokininlike peptides and their relation to 5-HT, CGRP, and bombesin immunoreactivities in the brainstem and spinal cord of lampreys.

The distribution of cholecystokinin (CCK)-like immunoreactivity in the brainstem and spinal cord of lampreys was studied by using CCK antisera with different properties. In the spinal cord, three separate systems reacted with CCK antisera: (1) A ventral and lateral fiber system descending from a group of neurons in the posterior reticular nucleus of the rhombencephalon was labeled by both a C-terminal-directed CCK antiserum and a monoclonal CCK antibody. (2) A dorsal root-dorsal column system of fibers originating from cell bodies in the dorsal root ganglia was labeled only by the C-terminal CCK antiserum. This CCK immunoreactivity could be abolished by preabsorption with calcitonin-gene-related peptide (CGRP), suggesting that it was due to cross-reactivity with a CGRP-like peptide. This system also contained 5-hydroxytryptamine (5-HT)-, bombesin-, and CGRP-like immunoreactivities. (3) An intraspinal system of 5-HT neurons was labeled with an antiserum to the midportion of CCK-33 but not by the other CCK antisera. The CCK labeling of this system was difficult to reduce by preabsorption with CCK peptide and thus appeared to be nonspecific. Groups of cell bodies in the middle reticular nucleus of the rhombencephalon, the reticular nucleus of the mesencephalon, and the hypothalamus were labeled by both the C-terminal and the monoclonal CCK antisera. The gut contained two types of CCK-like immunoreactivity, one of which appeared to be due to cross-reactivity with CGRP. A biochemical analysis showed that the content of CCK was low in the spinal cord compared to the brain, and these results agreed with the immunohistochemical findings.

Animals↗

Expression of eight neuropeptides in intraocular spinal cord grafts: organotypical and disturbed patterns as evidenced by immunohistochemistry.

The present study examines the distribution of several neuropeptides, as revealed by immunohistochemistry in the isolated cord. Fetal rat spinal cord was grafted to the anterior chamber of the adult Sprague-Dawley albino rats. After intraocular maturation for 2-3 months, the amount and distribution of somatostatin, neuropeptide Y, substance P, enkephalin, vasoactive intestinal peptide, peptide histidine-isoleucine, calcitonin gene-related peptide and cholecystokinin immunoreactive terminals and cell bodies were analysed using indirect fluorescence immunohistochemistry. The visualization of immunoreactive cell bodies in the grafts was enhanced using a novel intraocular colchicine treatment. In the graft a rich network of somatostatin-positive terminals was found with a high density in well-demarcated areas reminiscent of substantia gelatinosa of the dorsal horn of normal spinal cord. A large number of small- to medium-sized somatostatin neurons was found throughout the grafts without colchicine treatment. This is in contrast to normal spinal cord, where positive neurons were difficult to visualize without colchicine and were mainly confined to the dorsal horn. Neuropeptide Y had a distribution in the grafts similar to that of somatostatin and neuropeptide Y cells were found throughout the grafts without colchicine treatment. In normal spinal cord, neuropeptide Y-positive fibers were found mainly in substantia gelatinosa with a sparse network in the ventral horn. Enkephalin-positive fibers were found throughout the grafts. The distribution of fibers resembled that of somatostatin and neuropeptide Y with distinct zones of high fiber density in well-demarcated areas, whereas the density of nerve fibers in the rest of the graft neuropil was moderate to low. The distribution of substance P was similar to that of enkephalin. After colchicine treatment, both enkephalin- and substance P-positive cell bodies were visualized. In the intact spinal cord both peptides were seen in the entire gray matter with the highest concentrations in the superficial laminae of the dorsal horn. Antisera against calcitonin gene related-peptide, revealed a sparse terminal network and many large cells, which might represent motoneurons. A sparse network of varicose cholecystokinin-immunoreactive fibers was found evenly distributed in the grafts. In normal spinal cord a dense cholecystokinin-positive network of primary sensory afferent origin was found in the dorsal horn. In the grafts cholecystokinin cell bodies were seen after colchicine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Bladder exstrophy--anterior osteotomy of the pelvis--a new surgical technic for facilitating stabilization of the pelvis and abdominal closure].

The reconstruction of a stable anterior pelvic ring and the tension-free soft tissue closure is the key to a successful reconstructive surgery of the ectopic bladder. Instead of the commonly practised iliac osteotomy to achieve this goal we postulate the bilateral anterior osteotomy of the superior ramus of the pubic bone. The operative technique of this new method is described. The early results of four cases are discussed.

Abdominal Muscles↗

Glutamic acid decarboxylase- and peptide-immunoreactive neurons in cortex cerebri following development in isolation: evidence of homotypic and disturbed patterns in intraocular grafts.

Fetal parietal cerebral cortex was transplanted to the anterior eye chamber of adult Sprague-Dawley rats. After two to three months the grafts, with or without colchicine treatment, were subjected to immunohistochemical analysis using antibodies against cholecystokinin (CCK), somatostatin (SOM), neuropeptide tyrosine (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Cerebral cortex in situ of untreated and colchicine-treated rats was always analyzed in parallel. A dense plexus of CCK-immunoreactive fibers was distributed in all parts of the transplants, and after colchicine treatment a large number of CCK-positive cells was observed. These cells were markedly increased in number as compared to normal cortical tissue in colchicine-pretreated rats. The amount of NPY-immunoreactive cells was also markedly increased, whereas somatostatin-positive cells were found in numbers similar to those seen in cortex in situ. In the grafts only a few VIP- and PHI-positive fibers were seen with a few VIP-positive cell bodies, but no clearly discernible PHI-positive cells. A very dense plexus of GAD-positive fibers with an even distribution throughout the grafts was observed. Cortex in situ exhibited a lower density of GAD-immunoreactive fibers. Even after colchicine treatment the number of GAD-positive cells in the grafts was low. Using double-staining techniques, it was found that most of the few GAD-positive cells in the grafts were also NPY-positive, SOM-positive or, to a minor extent, CCK-positive. The present results demonstrate that several peptides and transmitter markers are expressed in cortical grafts in oculo, but marked differences in their expression can be observed in cortical tissue that has developed in isolation. Thus, the intraocular cortex graft, alone and in combination with other brain areas, should provide a useful model in which to study factors that regulate brain development.

Animals↗

Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells.

By use of the indirect immunofluorescence technique the distribution of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) has been analyzed in cervical and lumbar dorsal root ganglia of untreated and colchicine-treated rats. In addition, lumbar ganglia were examined 2 weeks after transection of the sciatic nerve. The occurrence of CGRP-positive cells in relation to ganglion cells containing substance P-, somatostatin-, galanin-, cholecystokinin (CCK)-, and vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucin (PHI)-LI has been evaluated on consecutive sections as well as using elution-restaining and double-staining techniques. CGRP-LI was observed in many ganglion cells of all sizes ranging in diameter from 15 microns to 65 microns. Thus, this peptide occurs also in the large primary sensory neurons. In contrast to the sensory peptides described to date, CGRP-positive cells constituted up to 50% of all and 70% of the medium-sized neurons, thus being the most frequently occurring peptide in sensory neurons so far encountered. Subpulations of CGRP-positive neurons were shown to contain substance P-, somatostatin-, or galanin-LI and some CGRP-positive neurons contained both substance P- and galanin-LI. In fact, most substance P-, somatostatin- and galanin-positive cell bodies were CGRP-immunoreactive. The coexistence analysis further revealed that galanin and substance P often coexisted and that some cells contained both substance P- and somatostatin-LI, whereas no coexistence between galanin and somatostatin has as yet been seen. VIP/PHI-LI was only shown in a few cells in untreated or colchicine-treated rats. However, after transection of the sciatic nerve numerous VIP/PHI-positive cells were observed, some of which also contained CGRP-LI. The present results indicate that a CGRP-like peptide is present in a wide range of primary sensory neurons probably not related to specific sensory modalities. Often this peptide coexists with other biologically active peptides. Taken together these findings suggest that CGRP may have a generalized function.

Animals↗

Microvascular orchiopexy.

In the period between 1981 and 1986, 22 microvascular testicular autotransplantations were performed on 18 patients at the Royal Manchester Children's Hospital. The preoperative assessment, the operative technique, and the follow-up results are discussed. Of 22 transplanted testes, four (18.2%) became partially or totally atrophic. The early results are very encouraging; however, only long-term postpubertal follow-up regarding both fertility and malignancy can reveal the real value of this operation.

Child↗