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Biomedical subjects

M de Jager

Publications and source records attributed to M de Jager.

11 recordsLinked to original sources

A rapid and simple method for cryopreservation of human liver slices.

1. Precision-cut liver slices represent a suitable and convenient in vitro preparation for studying metabolism and toxicity mechanisms of drugs and toxic chemicals. Particularly in the case of human liver slices, cryopreservation would enable more efficient utilization of this scarce and irregularly available tissue. 2. Liver slices from consecutive human livers were cryopreserved using a method previously developed for rat and monkey liver slices. This procedure involves incubation in 12% dimethyl sulphoxide for 30 min on ice and direct immersion into liquid nitrogen. 3. Functional integrity of cryopreserved human liver slices, as compared with that of fresh liver slices, was maintained at 66 +/- 8% (alanine aminotransferase activity retained in the slices), 78 +/- 7% (urea synthesis), 88 +/- 14% (testosterone hydroxylation), 84 +/- 7% (N-deethylation of lidocaine) and 88 +/- 10% (total O-deethylation of 7-ethoxycoumarin). The ratios of testosterone metabolites did not change on cryopreservation. 4. These results show that the cryopreserved human liver slices retained the measured drug metabolism activities. Therefore, this cryopreservation method is suitable for storing liver slices to be used for comparing drug metabolism patterns, at least qualitatively, between species.

Animals

The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa.

OBJECTIVE: To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout. DESIGN: Multicentre randomised controlled trial. SETTING: Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases. PARTICIPANTS: Women in labour at term with moderate or thick meconium staining of the amniotic fluid. INTERVENTIONS: Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible. MAIN OUTCOME MEASURES: Caesarean section, meconium aspiration syndrome and perinatal mortality. RESULTS: Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes. CONCLUSIONS: This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome.

Amnion

A randomised placebo controlled trial of oral misoprostol in the third stage of labour.

OBJECTIVE: To compare oral misoprostol 400 microg with placebo in the routine management of the third stage of labour. DESIGN: A double-blind placebo controlled trial. Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum. PARTICIPANTS: Low-risk women expected to deliver vaginally. METHODS: Women in labour were randomly allocated to receive either misoprostol 400 microg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded. MAIN OUTCOME MEASURES: Measured blood loss > or = 1000 ml within the first hour after birth. Use of additional oxytocics. RESULTS: The groups were well matched. Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35-1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64). CONCLUSIONS: Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited.

Administration, Oral

Fetal vibro-acoustic stimulation with a can--a clinical study.

OBJECTIVE: To assess the usefulness of the can as a fetal vibro-acoustic stimulator in the clinical environment. PATIENTS AND SETTING: 112 high-risk obstetric patients at Coronation Hospital, Johannesburg. METHOD: 161 vibro-acoustic stimulation tests with a can and 159 non-stress tests (NSTs) were performed. The results of the can test were compared with those of the NSTs and with fetal outcome at delivery. RESULTS: The can test showed poor sensitivity (5/9). Three of the 4 false-negative results were due to placental abruption that occurred subsequent to the can test. The ability of the can test to predict a reactive NST and good fetal outcome was 94% (negative predictive value). CONCLUSIONS: In view of the reasonable negative predictive value, the test should be evaluated further as a screening test at primary care level, where there are few or no cardiotocographic facilities.

Acoustic Stimulation

Validation of the Edinburgh Postnatal Depression Scale on a cohort of South African women.

UNLABELLED: Postnatal depression occurs in 10-15% of women. The Edinburgh Postnatal Depression Scale (EPDS) is a 10-item self-report scale designed specifically as a screening instrument for the postnatal period. It was initially validated for use in the UK, but has subsequently been validated for other communities. It has not been validated for an African community. OBJECTIVE: To determine whether the EPDS is a valid screening scale for depression in a Johannesburg community cohort. PARTICIPANTS AND SETTING: 103 women attending the postnatal clinic at Coronation Hospital, Johannesburg, South Africa. METHOD: The EPDS was validated against the Diagnostic and Statistical Manual (DSM-IV) criteria for depression. It was administered verbally to participants and translated into one of six South African languages where necessary. RESULTS: A threshold of 11/12 on the EPDS identified 100% of women with major depression and 70.6% of women with minor depression. For major and minor depression combined, sensitivity was 80%, specificity 76.6%, positive predictive value 52.6% and negative predictive value 92.2%. CONCLUSION: The EPDS, administered verbally, is a valid screening instrument in this urban South African community.

Cohort Studies

Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat.

Liposomes with diameters of 200 to 400 nm containing phosphatidylserine (PS) or phosphatidylglycerol (PG) were injected intravenously into rats. Two hours after injection, 75% of the injected dose of PS liposomes was found in the liver and only 10% found in the spleen, while 35% of the PG liposomes was found in the liver and as much as 40% was found in the spleen. Cell-isolation experiments revealed the following remarkable difference in the intrahepatic distribution between the two liposome formulations: the PS liposomes distributed in about equal amounts to Kupffer cells and hepatocytes, despite their size (200-400 nm) exceeding that of the endothelial fenestrae (average 150 nm), whereas the PG liposomes were only taken up by the Kupffer cells and not at all by the hepatocytes. Double-label studies, using liposomes in which the lipid-moiety was radio labeled with [3H]cholesteryloleylether ([3H]CE) and the water phase with [14C]sucrose, showed that the liposomes were taken up as intact particles. These observations were confirmed through electron microscopy by determining the in situ localization of liposome-encapsulated colloidal gold particles in thin sections of liver and spleen. The differences in organ distribution are ascribed to differences in opsonization patterns of the two liposomal surfaces. For the difference in intrahepatic distribution, we offer the following two explanations: the exploitation of the blood cell-mediated forced sieving concept and the indication of a PS-specific pharmacological effect on the dimensions of the fenestrations.

Animals

Primary care fetal assessment--low-cost fetal arousal testing.

Conventional vibro-acoustic stimulation tests require expensive vibro-acoustic stimulators and electronic monitoring equipment. Attempts to simplify the test have been made using an electric toothbrush and razor but even these simpler devices are not available in most primary care settings. We compared the sound pressure generated by a Corometrics 146 vibro-acoustic stimulator to that of an empty soft-drink can in an in vitro study. The can compared favourably to the conventional vibro-acoustic stimulator.

Acoustic Stimulation

Amnioinfusion.

Abnormal amniotic fluid volume may be both the result and the cause of complications at various stages of pregnancy. This review focuses on evidence from randomised trials of the effectiveness of amnioinfusion. Attempts to prevent the development of pulmonary hypoplasia by means of transabdominal amnioinfusion to correct severe oligohydramnios in the middle trimester of pregnancy have not been evaluated by randomised trials. Long-term transcervical amnioinfusion for prelabour rupture of the membranes has shown promising results in prospective studies, but has also not been subjected to randomised evaluation. Transcervical amnioinfusion during labour is a relatively simple procedure. Normal saline is infused through an intrauterine catheter, preferably one with a catheter-tip pressure transducer. Once an adequate volume of amniotic fluid has been achieved, it is maintained by means of a slow continuous infusion or repeated bolus infusions. Amnioinfusion has been used to prevent or treat fetal heart rate (FHR) decelerations thought to be due to oligohydramnios. In several rather small randomised trials, amnioinfusion has been associated with a reduction in FHR decelerations, caesarean sections, low Apgar scores, low umbilical arterial pH values and postpartum endometritis. Amnioinfusion has also been used to dilute thick meconium-staining of the amniotic fluid. In trials for this indication, amnioinfusion has been associated with similar benefits, and in addition a reduction in meconium presence below the vocal cords, meconium aspiration syndrome and the need for neonatal ventilation. Larger trials are needed to determine whether amnioinfusion is associated with an effect on perinatal mortality, and whether complications such as umbilical cord prolapse are increased.

Amnion