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P Juul

Publications and source records attributed to P Juul.

At least 19 recordsLinked to original sources
PubMed1992

Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats.

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.

Animals↗
PubMed1992

Athymic experimental animals in pharmaco-immunological research.

Immunodeficient animals--the nude mouse and the nude rat--allow studies of drug action and possible side effects without interference from the immune system. Comparative investigations in athymic and euthymic animals allowed us to elucidate the role of T-lymphocytes in the pathogenesis of streptozotocin-induced diabetes mellitus in mice, and the importance of NK-cells as effectors in guanethidine-induced sympathectomy in the rat. It is suggested that immunodeficient animals should be included in toxicological studies of xenobiotics.

Animals↗
PubMed1992

Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats.

Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but not prevent the initiation of an immunological reaction in the ganglia. Natural killer cells could only be identified in ganglia following guanethidine treatment alone. It is concluded that anti-asialo GM1 treatment can prevent the guanethidine-induced sympathectomy by eliminating the natural killer cells from the ganglia.

Animals↗
PubMed1990

Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy.

Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an infiltration of small inflammatory cells. By means of monoclonal antibodies these cells were identified. The number of B-lymphocytes increased following guanethidine in both athymic and euthymic rats. The number of T-lymphocytes increased to a great extent in euthymic rats, but was virtually missing in athymic rats. The number of NK-cells and monocytes/macrophages increased in both athymic and euthymic rats. The conclusion is, that guanethidine exerts a direct effect on sympathetic ganglion cells followed by a thymus-independent immune response.

Animals↗
PubMed1989

Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects.

The pharmacokinetics of orally administered idarubicin (22.5 mg/m2/week) and idarubicinol were studied for 12 weeks in 14 patients with breast cancer. Plasma concentrations were monitored for 72 hours after the first, fourth, and twelfth doses and trough concentrations after 1, 2, 3, 4, 5, 7, 11, and 12 weeks of treatment. The half-lives of idarubicin and idarubicinol were 19 and 60 hours, respectively. No time-dependent changes or cumulation were observed. The metabolic ratio showed little variation. The plasma AUCs of idarubicin and idarubicinol varied between patients but were fairly constant in individual patients. The sum of the plasma AUCs was lower in patients with rapid progression than in patients who responded to treatment. A correlation between this parameter and the relative decrease in the leukocyte counts was demonstrated (p less than 0.05). No correlation was found between the pharmacokinetic parameters and the time to final progression.

Administration, Oral↗
PubMed1989

Guanethidine-induced sympathectomy in the nude rat.

Guanethidine sulphate 40 mg/kg was administered intraperitoneally daily for 14 days to normal Lewis rats and athymic nude rats of a Lewis background (rnu/rnu). Histological examination of the superior cervical ganglia demonstrated a pronounced chromatolysis of the neurones and a loss of the major part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus-independent immune-response or by a direct toxic effect.

Animals↗
PubMed1987

Single or multiple doses of metronidazole and ampicillin in elective colorectal surgery. A randomized trial.

A randomized trial including 294 patients was performed to evaluate the prophylactic effect of single vs. multiple doses of antibiotics in elective colorectal surgery. All patients received 1.5 g metronidazole and 3.0 g ampicillin peroperatively and were randomized to: no further prophylactic antibiotic treatment, or ampicillin 1 g X 3 and metronidazole 0.5 g X 3 given intravenously during the second and third postoperative days. Deep wound infection was seen in 9/149 (6 percent) receiving a single dose and in 8/145 (6 percent) receiving multiple doses. No differences were found in the two groups between frequencies of anastomotic dehiscences, intra-abdominal abscesses, sepsis, and pulmonary infections. The two groups were similar according to distribution of sex, age, diagnosis, and type of surgery. A single peroperative dose of metronidazole and ampicillin is a simple and satisfactory antibiotic prophylaxis in elective colorectal surgery.

Adolescent↗
PubMed1985

Topical ampicillin in addition to a systemic antibiotic prophylaxis in elective colorectal surgery. A prospective randomized study.

Prophylactic use of topical ampicillin in addition to intravenous ampicillin and metronidazole was studied in a randomized trial including 203 consecutive patients undergoing elective colorectal surgery. All received ampicillin, 1 g X 3, and metronidazole, 0.5 g X 3, intravenously for at least three days from induction of anesthesia, and 105 also received topical ampicillin, 1 g, in each of the surgical wounds. Deep wound infection or dehiscence was seen in 12 of 105 having both administrations of antibiotics, and in nine of 98 having only intravenous antibiotics. The two groups were similar according to distribution of sex, age, type of surgery, and efficiency of bowel preparation. Topical ampicillin should be omitted in elective colorectal surgery when systemic prophylaxis with ampicillin and metronidazole is used.

Administration, Topical↗
PubMed1985

Spontaneous rupture of the urinary bladder.

Two cases of spontaneous bladder rupture are presented. The aetiology, clinical picture and treatment are described. The mortality rate is high in this condition, and clinicians should be aware of the diagnosis in differentiation of abdominal emergencies with urinary symptoms.

Adult↗
PubMed1984

Systematic within-person variation in the bioavailability of various drugs in healthy volunteers.

The relative bioavailability of 22 registered pharmaceutical specialities compared to one or more generic equivalents was investigated in 50 human volunteers using randomized cross-over trials. The data were reassessed with regard to individual behaviour in different experiments and with different drugs. The pharmacokinetic behaviour (Cmax, Tmax, and AUCo-t) of the volunteers exhibited consistent patterns, which were not attributable to chance. It is concluded that the cross-over design is necessary in conducting relative bioavailability studies.

Adult↗