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Biomedical subjects

L Olsen

Publications and source records attributed to L Olsen.

At least 73 records · Page 4Linked to original sources

Gastrin-releasing peptide stimulation of corticotropin secretion in male rats.

Gastrin-releasing peptide (GRP; mammalian bombesin) may be involved in the neuroendocrine regulation of pituitary hormone secretion. We investigated the effect of GRP on ACTH secretion in conscious male rats. GRP (7-700 pmol) stimulated ACTH secretion dose-dependently after intracerebroventricular (icv) administration but had no effect after iv administration. GRP infused icv in a dose of 7 pmol, which alone increased ACTH 1.5-fold, potentiated the ACTH-releasing effect of arginine vasopressin (AVP; 80 pmol iv) and corticotropin-releasing hormone (CRH; 100 pmol iv). A higher dose of GRP (70 pmol icv), which stimulated ACTH secretion 2-fold, potentiated the effect of 80 and 400 pmol AVP iv, but had only additive effect on the ACTH response to 800 pmol AVP iv or 100 pmol CRH iv. GRP infused iv in a dose of 210 pmol, which in itself had no effect on ACTH secretion, potentiated the ACTH-stimulating effect of AVP and CRH approximately 2.5-fold. The effect of GRP (icv or iv) on AVP or CRH-stimulated ACTH release was only slightly smaller than the effect of combined administration of AVP and CRH (80 + 100 pmol iv). The ACTH-stimulating effect of GRP (700 pmol icv) was inhibited about 60% by pretreatment with either CRH or AVP antiserum and prevented by combined pretreatment with the antisera. The results indicate that: 1) GRP affects ACTH secretion indirectly at a suprapituitary level--possibly in the hypothalamus--by stimulating the release of AVP and CRH to the pituitary portal blood; and 2) GRP acts directly at the pituitary level to augment the effect of AVP and CRH on the corticotrophs. We suggest that GRP is involved in the multifactorial regulation of ACTH secretion.

Adrenocorticotropic Hormone↗

Urethral reconstruction with a new synthetic absorbable device. An experimental study.

Four centimeters of the canine urethra was replaced by a graft consisting of a polyglactin fiber mesh tube, coated with polyhydroxybutyric acid. Microscopic examination 8-12 months later showed almost complete regeneration of the urethral epithelium and the adjacent connective tissue. The neo-urethra was patent and there were no anastomotic strictures, nor was there any inflammatory reaction around the urethra. The validity of this concept in humans remains to be proved.

Animals↗

Epitope mapping of HIV-1 reverse transcriptase with monoclonal antibodies that inhibit polymerase and RNase H activities.

Lysates from E. coli expressing HIV-1 reverse transcriptase (RT) as a TrpE fusion protein were used for immunization of BALB/c mice. Twenty hybridomas producing monoclonal antibodies (MAbs) recognizing the RT part of the TrpE-RT fusion protein by Western blot analysis were isolated. Of these, 18 were reactive in immunofluorescence assays when tested on HIV-infected cells. Twelve MAbs were reactive with both the p66 and p51 fragments of RT, while 6 of the MAbs were reactive only with the p66 band, indicating specificity for the C-terminal (RNase H) region of RT. Mapping of the monoclonal antibody binding sites was performed using deletion and insertion mutants of recombinant RT. The antibodies bound to five distinct regions within amino acid sequences 190-560 of RT. In order to map functionally important regions of the RT molecule, the MAbs were tested for their ability to interfere with the polymerase and RNase H activities of the polypeptide. MAbs binding to two different epitopes in the polymerase domain were found to inhibit the polymerase activity. Of these, three MAbs also inhibited the RNase H activity. Two MAbs binding to the same epitope in the RNase H region inhibited RNase H activity and further mediated an effect on the polymerase activity.

Amino Acid Sequence↗

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive disorder: clinical reports and review of the literature.

We present 2 new patients with the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), review the literature, and discuss the prenatal diagnosis and treatment. MMIHS, as reported in 43 cases, is usually lethal. Most children die during the first year of life, and only 3 children survived their first year. We report the 6th pair of sibs with the disease. Overall, 17 patients reported have had sibs with MMIHS or the parents were consanguineous; 4 times the parents were first, cousins, confirming that this is an autosomal recessive disorder. The present 2 children, whose parents also were first cousins, were of different sex. They had typical MMIHS with abdominal distension due to pronounced megacystis, hydronephrosis, microcolon, and microileum, involving the distal part of the ileum, malrotation of the gut, and intestinal hypoperistalsis. Neither surgery nor medical treatment was successful and the children died at the age of 19 days and 2 1/2 months, respectively. There is no cure for the disease. However, a new protkinetic drug, Cisapride might be worth trying in these cases. Prenatal ultrasound diagnosis of MMIHS might be possible.

Abnormalities, Multiple↗

Free autogenous muscle transplantation in children. Long-term results.

For more than 15 years we have been using free muscle transplantation in the treatment of anal incontinence in children. This method implies transposition of a striated muscle, usually the palmaris longus, two weeks after denervation, to the perirectal area as a U-sling around the rectum corresponding to the location of the so-called puborectalis muscle. We have now evaluated the long-term results in all 26 children operated on by this method. Before the operation all children were totally incontinent after a primary repair. At follow-up after an average of 11 years and 4 months, 60% of the cases were regarded as good, 16% as fair, 8% as improved and 16% as failures. In our opinion, free muscle transplantation offers a good chance of achieving acceptable continence in a majority of incontinent children.

Adolescent↗

Mediation of the stress-induced prolactin release by hypothalamic histaminergic neurons and the possible involvement of vasopressin in this response.

We investigated the role of histamine (HA) in the neuroendocrine regulation of PRL secretion in conscious male rats. Blood samples were obtained by decapitation of the animals at 0 min. Intracerebroventricular infusion of HA (34-540 nmol at -15 min) stimulated PRL secretion dose dependently with an ED50 of approximately 135 nmol. Inhibition of neuronal HA synthesis by the specific histidine decarboxylase-inhibitor (S)alpha-fluoro-methylhistidine (alpha FMH; 100 mumol/kg ip at -6 h or 400 mumol/kg ip at -20 h and -6 h) caused a 50% reduction (P less than 0.01) in the PRL response to 5 min of restraint stress. Inhibition of neuronal HA metabolism by the specific histamine-methyltransferase-inhibitor SKF-91488 (400 and 800 nmol icv at -20 min) augmented the restraint stress-induced PRL release 26% and 37%, respectively (P less than 0.05). The two enzyme inhibitors had no or only modest effect on the basal PRL secretion. Pretreatment with a specific antiserum (0.5 ml) to arginine vasopressin (AVP) or an AVP antagonist (25 nmol) administered iv at -20 min inhibited the PRL response to HA (270 nmol icv) 80% and 45%, respectively (P less than 0.01) and inhibited the PRL response to restraint stress 70% (P less than 0.01). In contrast, pretreatment with a specific oxytocin (OT) antagonist (50 nmol) had no effect on the HA- or stress-induced PRL release. The AVP antiserum showed less than 0.0003% cross-reactivity with OT, and radiolabeled OT did not bind to serial dilutions of plasma from rats treated with the AVP antiserum. The AVP antiserum or the AVP antagonist almost prevented the PRL release induced by iv infusion of 800 pmol AVP or a posterior pituitary extract. Infusion of AVP (24-800 pmol iv at -15 min) stimulated PRL secretion dose dependently. However, the dose of AVP (800 pmol) required to induce an increase in plasma PRL similar to that obtained by HA-stimulation, led to a rise in plasma AVP which was approximately 1000-fold higher than that induced by HA, which increased plasma AVP 2-fold. Restraint stress had no effect on the plasma AVP level. We conclude that neuronal HA participates in the mediation of the PRL response to stress and that the stress- and HA-induced release of PRL may involve AVP, whereas an involvement of OT seems unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Tissue expansion facilitates operation of large myelomeningoceles.

Two children had delayed operations for large myelomeningoceles. As a preparatory operation one silicon tissue expander was inserted on each side of the lesion and successively inflated by weekly injections of saline. After an expansion time of 5 to 6 weeks the definitive procedure was performed. The newly formed fibrous capsule greatly facilitated the reconstruction of the spinal canal. The surplus of skin and subcutaneous tissue allowed the large defects to be easily close in the midline. Both children managed quite well postoperatively.

Cerebrospinal Fluid Shunts↗

In vitro detection of enterococcal vancomycin resistance.

By using agar dilution as the standard method, we determined the ability of broth microdilution, disk diffusion, and an automated system (AMS Vitek) to detect three different levels of vancomycin resistance among six enterococcal isolates. Enterococcus gallinarum AIB-38 and AIB-39 exhibited low-level resistance (MIC, 16 to 32 micrograms/ml) that was detected only by agar and broth dilution methods. E. faecalis V583, E. faecium AIB-42, and E. faecalis AIB-41 showed moderately high-level resistance (MIC, 128 to 256 micrograms/ml) that was detected by dilution methods but not by disk diffusion unless prolonged incubation or an inoculum 10-fold greater than the standard was used. Similarly, this level of resistance was detected by AMS Vitek only when an inoculum 10-fold larger than recommended was used. The high resistance demonstrated by E. faecium AIB-40 (MIC, 2,048 micrograms/ml) was readily detected by all methods studied. Variation in the ability of different methods to detect vancomycin resistance among enterococci complicates monitoring the incidence of these organisms and could result in very major susceptibility reporting errors.

Drug Resistance, Microbial↗

Endodermal sinus tumour in girls--improved survival in metastatic disease.

In girls, endodermal sinus tumours are rare and malignant germinal tumours. They are highly lethal and it has previously been considered in cases with distant metastases at the time of diagnosis, that there is no satisfactory therapy. However, the rapid development during the last years of highly effective chemotherapeutic agents seems to have improved the survival rate. Already there are a few reports of surviving patients with metastatic disease. In our material of five girls with endodermal sinus tumour, one with metastatic disease has been treated according to a new protocol with combination therapy (cis-VAB). Four years after the operation she is alive and well without any sign of recurrence.

Antineoplastic Combined Chemotherapy Protocols↗