The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

Surgical and oncologic principles of the removal of the rectum

Excision of the rectum should take in account that the main lymphatic spread follows the cranial route and that dissection of the rectal wall should be performed across its adjacent anatomical lamellae. It is not clear whether an extensive pelvic dissection and high ligature of the inferior mesenteric artery are beneficial. Spontaneous or iatrogenic perforation of the tumour considerable increases the incidence of local recurrence. The frequency of postoperative urinary and sexual dysfunction ranges from 3.5-57% and 14-38% respectively. The reported surgical mortality averages 5-6%.     

Potentiation of cholinergic activity with pyridino[1,2-a]imidazo[5,4-b]indole: in vitro studies

1. Effects of a novel imidazoindole derivative on cholinergic function were studied in isolated tissue preparations. 2. The compound demonstrated a dose-dependent (10(-11)-10(-9) potentiation (20-60%) of acetylcholine induced tension in guinea pig ileal tissue. 3. Increases in the size of end-plate potentials and nerve evoked muscle twitches were observed in frog nerve-skeletal muscle preparations. 4. Cholinesterase activity was not inhibited. 5. The results suggest that the compound has actions at the post-synaptic muscarinic receptor complex in smooth muscle and causes pre-synaptic increases in ACh release at the neuromuscular junction.     

Injuries of the small and large intestine following blunt abdominal trauma

From 1979 to 1987 1428 patients with blunt abdominal trauma were treated in the Department of Surgery of the University of Freiburg; 119 patients had intestinal injuries. They were mainly young adults who had sustained a car accident. 71.3% of the small bowel injuries were overseen, 14.2% needed resection, and in 14.5% an operative procedure was not necessary. The surgical procedure for colonic injuries has to be chosen with regard to the age and general condition of the patient, to the severity of the trauma, to associated injuries and to the stage of peritonitis. Accordingly, 18% of the patients were treated with and 58% without a protective colostomy, 24% could be treated conservatively. Mortality and morbidity correlated with the severity of associated injuries. Morbidity was also dependent on the time interval between accident and operative therapy.     

Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

Bradykinin-induced release of PGI2 from aortic endothelial cell lines: responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase.

1. Bradykinin (100 nM) triggers release of nitric oxide and prostacyclin from both AG07680A and AG04762 bovine cultured aortic endothelial cells. The exposure of these cells to bradykinin is in each case associated with a striking rise in intracellular calcium ion concentration. 2. Exposure of AG07680A cells to 250 nM ionomycin was followed also by a significant release of prostacyclin, whereas 250 nM ionomycin had no capacity to stimulate release of prostacyclin from AG04762 cells. 3. There was a similar concentration-dependent increase in intracellular calcium ion concentration on exposure of AG07680A and AG04762 cells to ionomycin. 4. Exposure of AG04762 cells for 10 min to staurosporine produced a concentration-dependent inhibition (IC50 = 107 +/- 14 nM) in bradykinin-stimulated prostacyclin release. There was no similar inhibitory effect of staurosporine in AG07680A cells. 5. Bradykinin (10 nM) triggered release of nitric oxide from both AG07680A and AG04762 cells, and the effect was not inhibited by 500 nM staurosporine. There was a similar ionomycin-dependent release of nitric oxide from both cell types. 6. These results identify a common pathway for bradykinin-dependent nitric oxide release from both AG07680A and AG04762 cells, involving increases in intracellular calcium ion concentration. In contrast, the bradykinin-dependent release of prostacyclin may involve one of two pathways (involving an increase in intracellular calcium or activation of a staurosporine-sensitive kinase), and the two pathways are selectively exploited in AG07680A and AG04762 cells, respectively.