The impact of an obstetrician-led, labor ward critical care unit: A prospective comparison of outcomes before and after establishment.

OBJECTIVE: To investigate the outcomes of critically ill obstetric patients managed in a obstetric critical care unit in South Africa. METHODS: Patients with severe maternal morbidity managed in the labor ward of Tygerberg Hospital were studied over three months before the establishment of the obstetrician-led obstetric critical care unit. One year later, patients managed in the obstetric critical care unit were studied using the same methods. The primary outcome measures were maternal morbidity and mortality. RESULTS: In the before-obstetric critical care unit prospective audit 63 patients met criteria for obstetric critical care. During the second period 60 patients were admitted to the obstetric critical care unit. There were no significant differences between the groups in baseline characteristics, admission indications or Acute Physiology and Chronic Health Evaluation scores. Continuous positive airway pressure (p < 0.01) was utilized more in the second group. Seven deaths occurred in the first, but none in the second group (p = 0.01). CONCLUSION: The establishment of an obstetrician-led obstetric critical care unit facilitated a decrease in maternal mortality.Trial registration: Not applicable.

Outcome of Pregnancy in the Morbidly Obese Woman

Background: Obesity is a growing global health problem. In South Africa; more than half of the adult women are overweight and almost 30are obese. The problems associated with obesity; such as diabetes; hypertension; thrombo-embolism and coronary heart disease; are well described in the non-pregnant population; but the condition itself holds specific risks during the ante-; intra- and postpartum periods of the pregnant woman. Of particular concern is the intrapartum period. Complications such as slow progress during labour and increased rates of caesarean section are best addressed proactively. For this reason certain sources advocate that all morbidly obese women be referred for evaluation of the pregnancy and planning of labour and delivery by an anaesthetist and a specialist obstetrician. The aim of this study was to determine whether morbidly obese women are at increased risk of adverse outcomes; compared to women with a normal body mass index (BMI). Methods: A case control study design was used. In this study a normal BMI was defined as 20-25 kg/m2 and morbid obesity as a BMI of = 40 kg/m2. The BMI was calculated from the weight and height measured at the booking visit. The cases in this study comprised the first hundred morbidly obese women seen at the Obstetric Special Care Clinic in Tygerberg Hospital (TBH); a secondary and tertiary referral centre. The controls (n = 209) were women with normal BMIs and singleton pregnancies who booked as low-risk patients at the Bishop Lavis Midwife Obstetric Unit (MOU) during the same calendar period. A minimum ratio of 2:1 controls-to-case was used; with controls also matched for primi- or multiparity. Patients booking at the MOU with significant obstetric risk factors are referred to TBH for antenatal care. These women were not considered as controls. However; low-risk women who met the inclusion criteria at booking and who subsequently developed risks or complications were included; as the selection was done according to findings at the booking visit. The main outcomes to be determined were: ante-; intra- and postpartum maternal complications; rate of epidurals; and perinatal outcomes. Results: Women in the morbidly obese group were significantly older (p 0.001) and of higher parity (p 0.001) than those with normal BMIs. There was no difference in the numbers of primigravidae. Significantly more women in the morbidly obese group had experienced at least one miscarriage (p received it. During delivery; perineal damage was more common in morbidly obese women (p 0.001) and their babies were significantly larger (p 0.001). There was one perinatal death. Conclusions: Morbidly obese women experienced increased complications during pregnancy and childbirth. Due to the high rate of caesarean sections and the potential difficulties of emergency anaesthesia among these women; epidural anaesthesia during labour should be planned and administered as often as possible

Reduced activation of peripheral blood neutrophils after late-phase asthmatic responses but not in mild stable asthma.

BACKGROUND: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations. OBJECTIVE: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations. METHODS: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined. RESULTS: No differences were detected in adhesion molecule expression and ROS production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations were found between decreases in CD11b and the severity of the LAR (r = 0.9; p < 0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p < 0.05). Again, this measurement was significantly associated with reductions in PEF (r = 0.5, p < 0.03). CONCLUSIONS: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung.

Mammalian actin-related protein 2/3 complex localizes to regions of lamellipodial protrusion and is composed of evolutionarily conserved proteins.

Human neutrophils contain a complex of proteins similar to the actin-related protein 2/3 (Arp2/3) complex of Acanthamoeba. We have obtained peptide sequence information for each member of the putative seven-protein complex previously described for Acanthamoeba and human platelets. From the peptide sequences we have identified cDNA species encoding three novel proteins in this complex. We find that in addition to Arp2 and Arp3, this complex contains a relative of the human (Suppressor of Profilin) SOP2Hs protein and four previously unknown proteins. These proteins localize in the cytoplasm of fibroblasts that lack lamellipodia, but are enriched in lamellipodia on stimulation with serum or platelet-derived growth factor. We propose a conserved and dynamic role for this complex in the organization of the actin cytoskeleton.

Behavioural changes in children following minor surgery--is premedication beneficial?

One hundred and twenty-three male children, aged one to ten years, were studied to determine the influence of premedication on changes in patterns of behaviour following hospitalization for repair of inguinal hernias. Four comparable groups were selected for premedication regimen: (1) A control group without premedication; (2) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg and droperidol 0.15 mg/kg; (3) oral midazolam 0.45 mg/kg; (4) intramuscular midazolam 0.15 mg/kg. Standard inhalational anesthesia was used and caudal blocks employed for analgesia. The parents returned a questionnaire at two weeks. Changes in behaviour were reported in 78% of the children and overall, premedication showed little benefit. However, midazolam premedication was associated with a significantly lower incidence of night-time crying and awakening, compared with no premedication. Only for night-time crying and day-time toilet training did age below five years prove to be a significant contributing factor.

Oral midazolam in paediatric premedication.

In a premedication study involving 135 children, aged 1-10 years, four regimens were investigated: (i) no premedication; (ii) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg, droperidol 0.15 mg/kg (TMD); (iii) intramuscular midazolam (Dormicum; Roche) 0.15 mg/kg; and (iv) oral midazolam 0.45 mg/kg. All premedications were given 60 minutes before a standard halothane anaesthetic. No impairment of cardiovascular stability occurred but after premedication the mean oxygen saturation decreased by 1.6% and 1.1%, respectively, in the intramuscular midazolam and TMD groups. Overall, children under 5 years of age behaved less satisfactorily in the holding room and at induction, than those over 5 years (P less than 0.01). Midazolam, intramuscularly and orally, produced more satisfactory behaviour than the other two regimens (P less than 0.05) and, combined with a 70% more rapid recovery than the TMD regimen (P less than 0.05), suggests that oral midazolam is a more effective paediatric premedication agent than placebo or TMD.

Midazolam and amnesia in pediatric premedication.

One hundred and twenty-eight children aged three to ten years, were studied to determine the effect of premedication on amnesia for the preanesthetic period. Four comparable groups were used: A control group, no premedication; oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg plus droperidol 0.15 mg/kg (T.M.D.); oral midazolam 0.45 mg/kg; intramuscular midazolam 0.15 mg/kg. Amnesia was tested for four pictorial facts, and for induction of anesthesia. For pictorial facts, both routes of midazolam administration gave a sixty percent incidence of amnesia compared with sixteen percent in the control group (p less than 0.001). The T.M.D. premedication provided a forty-three percent incidence, also better than the control group (p less than 0.05). Induction was remembered by fifty percent of the midazolam children compared with sixty-six percent of the T.M.D. group (p greater than 0.05) and eight-one percent of the control group (p less than 0.05). The potential advantages of amnesia in pediatric premedication are discussed.

Allografted keratinocytes used to accelerate the treatment of burn wounds are replaced by recipient cells.

Cultured keratinocytes were used as allografts on burn wounds in two patients. In both patients successful covering of the wounds was obtained. DNA fingerprinting of the epidermis covering the wounds 21 days later showed that the cultured keratinocytes were replaced by the patients' cells.

The pharmacokinetics of midazolam in paediatric patients.

A serum concentration profile study on midazolam in children was done. Fifty six children aged 3-10 years took part. The routes investigated were intravenous, intramuscular, rectal and oral at 0.15 mg.kg-1, and the oral at 0.45 mg.kg-1 and 1 mg.kg-1. Serum concentration levels for 5 h were studied using gas liquid chromatography. The volume of distribution, Vss, was 1.29 l.kg-1, the elimination half-life 1.17 h and the serum clearance 9.11 ml.kg-1.min-1. Peak serum concentrations for the intramuscular, rectal and oral routes were at 15 min, 30 min and 53 min respectively. Bioavailability was 87%, 18%, 27% respectively at a dose of 0.15 mg.kg-1. The oral route bioavailability halved to 15% at the two higher doses. Bioequivalence was present between the 0.15 mg.kg-1 intramuscular dose and the 0.45 mg.kg-1 oral dose from 45 to 120 min.

Oligomeric substances in ampicillin preparations. A comparison of Penbritin, Famicillin and Petercillin.

An investigation into the presence of potentially harmful oligomers in formulations of ampicillin for parenteral administration available in the RSA was undertaken by means of high-pressure liquid chromatography. Significant differences were found to exist between formulations.

Beneficial effects of adenosine triphosphate-MgCl2 administered intravenously to rabbits subjected to haemorrhagic shock.

The beneficial effects of adenosine triphosphate (ATP)-MgCl2 administered as a bolus following fluid infusion or in combination with the infusion fluid were investigated in rabbits subjected to severe but reversible haemorrhagic shock. ATP-MgCl2 treatment led to a significant improvement of the metabolic functions of lung and liver tissue. Kidney tissue showed the same tendency, but the improvement did not reach significant levels. The release of lysosomal enzymes in vivo was retarded after treatment but not stopped. The mean arterial pressure was kept at a relatively constant level when ATP-MgCl2 was infused slowly. Administration as a bolus resulted in an immediate dramatic drop in pressure, followed by recovery and then a gradual decrease to levels which appeared to be incompatible with survival.

Beneficial effect of naloxone on in vitro tissue metabolism after hemorrhagic shock.

A rabbit model of hemorrhagic shock is used in assessing the use of naloxone as an adjunct in the treatment of hemorrhagic shock. In vitro oxidation rates of labelled glucose are used as parameters of early tissue damage. Naloxone, given as an adjunct to volume replacement, significantly improves the in vitro capabilities of lung and liver tissues, but has no effect on kidney cortex. Changes in MABP are not affected by naloxone in this rabbit model, and serum lysosomal enzyme activity is not significantly improved. It is proposed that naloxone exerts some of its beneficial effect at the cellular level.

Experimental evaluation of the prophylactic and therapeutic effects of hydrocortisone in haemorrhagic shock.

The prophylactic and therapeutic effects of hydrocortisone (50 mg/kg) in severe haemorrhagic shock were evaluated by metabolic, biochemical and haematological investigations in a rabbit model. It was found that administration of hydrocortisone prior to severe haemorrhage had no beneficial effect on any of the values measured. Owing to haemoconcentration and marked mobilization of leucocytes it would appear that in pretreated animals the magnitude of the hypoxia was increased and led to greater tissue damage and higher levels of lysosomal enzymes than in rabbits which had not received pretreatment with hydrocortisone. On the other hand, hydrocortisone therapy combined with volume replacement 1 hour after the haemorrhagic insult had several beneficial effects. The metabolic capacity of liver and kidney tissues was improved, the lysosomal concentration remained within normal limits, and the mean blood pressure and pulse pressure were maintained better than in controls. However, it would appear that this beneficial effect is only exerted on tissue still in a reversible state of shock. There is therefore no beneficial effect on lung tissue metabolism, the lungs being more sensitive to hypoxic damage than either liver or kidney tissue. Administration of hydrocortisone results in the immediate release of endotoxins into the circulation. This might be due to its vasodilatory action on the microcirculation of the intestinal viscera.

Haemorrhagic shock--metabolic parameters for the assessment of damage in lung, liver and kidney tissue.

Changes in catabolic and biosynthetic parameters measured in vitro were used as criteria to assess the degree of damage in tissues after an animal was exposed to severe haemorrhagic shock for periods of 1 and 2 hours (blood loss 36,8%, blood pressure 30 +/- 5 mmHg). The biosynthetic capacity of lung tissue, as determined by the incorporation of 1-14C-palmitate into total lung lipids, declined significantly with time. This reduction correlates well (r =0,99) with the rate of decline in 14CO2 production from 1-14C- and 6-14C-glucose oxidation as well as with the decline in the rate of oxygen uptake. Any one of these parameters could therefore be used as an index of the degree of tissue damage due to haemorrhagic shock. Comparing the rates of decline in 14CO2 production from 1-14C-glucose by lung, liver and kidney tissue from the same animal after haemorrhagic insult for 1 hour, lung tissue appeared to be the most sensitive to hypoxia and kidney the least so. However, 2 hours after severe haemorrhage, i.e. near the terminal phase, the rate of 14CO2 production from 6-14C-glucose by liver tissue decreased dramatically by more than 53% of the control value. Apart from kidney and lung dysfunction, irreparable liver damage probably plays a major role in the fatal course of severe haemorrhage.

An organ culture of postnatal rat liver slices.

A technique for the organ culture of postnatal and adult rat liver has been developed. Liver slices, 0.3 mm thick, were maintained in Conway units at the interphase between medium and a 95% O2:5% CO2 atmosphere. Postnatal liver in culture for up to 72 h had healthy hepatocytes throughout the explants; if adult liver was used the upper 0.2 mm was healthy after 24 h. These slices incorporated tritiated orotate and leucine into trichloroacetic acid-precipitable material. Incorporation of orotate was shown to be spread over the entire slice of neonatal liver. Culturing did not alter the potassium ion content of postnatal liver. Tyrosine aminotransferase activity in liver slices from postnatal, adult, and adrenalectomized adult rats was stimulated by glucocorticoids and dibutyryl cyclic AMP. Cycloheximide and actinomycin D prevented this response. Further, cortisol exerted a permissive effect on the stimulation of tyrosine aminotransferase activity by dibutyryl cyclic AMP in slices from adrenalectomized rats. Induction of urea cycle enzymes by cortisol was demonstrated in cultures of liver from adrenalectomized adult animals.

Dietary and hormonal regulation of urea cycle enzymes in rat liver.

When 6-week-old rats fed normal diet (22% protein) were transferred to 10 and 75% protein diet, the levels of urea cycle enzymes showed decreases and increases respectively. The activities expressed as units per gram wet weight of liver had not stabilized after 7 days on the new diet; the corresponding specific activities were closer to leveling off. Four daily injections of cortisol raised CPS, ASS, and arginase. The percentage increases were greater on a 10 than on a 75% protein diet. Adrenalectomy of rats fed 10% protein decreased all urea cycle enzymes; on 75% protein, only arginase decreased. All enzymes could be raised to control levels within 24 h by three injections of cortisol. Thyroxine produced only slight increases in urea cycle enzymes. On a 10% protein diet, all five enzymes were raised by thyroidectomy, and further raised by injection of thyroxine.