PLASMA CONCENTRATIONS OF BUPIVACAINE DURING CONTINUOUS EPIDURAL ANALGESIA IN LABOUR: THE EFFECT OF ADRENALINE

Continuous epidural analgesia has been provided for eighteenpatients during the first and second stages of labour. Ninepatients received bupivacaine 0.5 per cent with adrenaline 5µg/ml, and nine bupivacaine alone, using a double-blindtechnique. The initial dose of bupivacaine was 30 mg, repeatedand increased as necessary. A total of fifty-nine doses wasgiven. Plasma concentrations of bupivacaine were measured inthe mother throughout the blockade, and in the baby at delivery.The duration of action of bupivacaine was not significantlyprolonged by adrenaline, though plasma concentrations were significantlyreduced 20 minutes after the first dose and 40 minutes afterthe second. In neither treatment group did bupivacaine accumulatemarkedly in maternal plasma unless the second stage necessitatedincreased doses. Neonatal bupivacaine concentrations were alwayslow and neonatal: maternal ratios increased by the use of adrenaline.It is thus uncertain whether adrenaline offered a significantadvantage except with large doses of bupivacaine, when it reducedthe likelihood of maternal intoxication.     

Breast-feeding, gastrointestinal and lower respiratory illness in the first two years

ABSTRACT. The relationships between breast-feeding practices and the rates of gastro-intestinal and lower respiratory illness during the first two years of life were examined for a birth cohort of New Zealand infants. During the first four months, there were significant tendencies for rates of gastro-intestinal illness to decrease with increasing duration of breast feeding. These trends remained significant when the effects of a number of social and familial factors were taken into account. There was no association between duration of breast-feeding and rates of gastro-intestinal illness beyond four months. Prolonged breast-feeding was associated with significantly lower rates of lower respiratory illness during both the first and second years. However, when the effects of social and familial factors were taken into account the apparent associations between duration of breast-feeding and rates of lower respiratory illness became non-significant. The implications of these findings are discussed.     

Studies on uterine tract infections and the IUCD with special reference to actinomycetes

Summary. Since the advent of the plastic IUCD, an increasing number of patients with clinical pelvic actinomycosis have been reported in the literature and in a very much larger number of women, actinomycetes have been identified in cervical smears, either by Papanicolaou stain or specific immunofluorescence. After a 3-year study, we have concluded that actinomycetes can readily be cultured when the growth of more rapidly growing anaerobes is inhibited by metronidazole and anaerobic culture is continued for up to 14 days. We consider that actinomycetes form part of a polymicrobial anaerobic infestation developing in the presence of a foreign body. The organisms are found almost exclusively in women who have used all-plastic IUCDs for a long term and, from a continuing study, it is apparent that most disappear rapidly when the plastic device is removed or replaced by a copper device. Significant symptomatic evidence of infection is found in a small proportion of patients who are actinomycete-positive.     

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Regulation of neutrophil migration and superoxide production by recombinant tumor necrosis factors-alpha and -beta: comparison to recombinant interferon-gamma and interleukin-1 alpha

We compared the ability of recombinant human tumor necrosis factor- alpha (rHuTNF-alpha) and tumor necrosis factor-beta (rHuTNF-beta) to stimulate polymorphonuclear neutrophil (PMN) migration and superoxide production. Significant PMN migration occurred across polycarbonate filters after stimulation with rHuTNF-alpha at concentrations ranging from 10(-7) to 10(-10) mol/L and at 10(-7) to 10(-8) mol/L for rHuTNF- beta and N-formylmethionyl-leucyl phenylalanine (FMLP), whereas recombinant human interferon-gamma was only minimally active at 10(-7) mol/L and recombinant human interleukin-1 alpha was inactive at the doses tested. In addition, antibodies to rHuTNF-alpha completely inhibited rHuTNF-alpha but not rHuTNF-beta or FMLP-induced PMN migration. Combinations of rHuTNF-alpha and rHuTNF-beta (at similar molar concentrations) stimulated PMN migration levels comparable to that obtained with rHuTNF-alpha alone. Checkerboard analyses performed by placing different concentrations of rHuTNF-alpha and rHuTNF-beta above and below polycarbonate filters of microchemotaxis chambers demonstrated that rHuTNF-alpha and rHuTNF-beta stimulated both chemotactic and chemokinetic responses by PMN. Additional studies demonstrated that 1 X 10(-8) mol/L rHuTNF-alpha and 3 X 10(-9) mol/L rHuTNF-beta (which represents 10(4) U/mL of each cytokine) were similar in their ability to induce superoxide production by PMNs; however, at ten- to 100-fold lower molar concentrations (10(3) and 10(2) units), rHuTNF-alpha was significantly more active than rHuTNF-beta. At the doses tested, both cytokines were less active than phorbol myristate acetate at stimulating O2- release. The results demonstrate that rHuTNF- alpha and rHuTNF-beta differ quantitatively but not qualitatively in their effects on PMN functions in vitro and suggest that rHuTNF-beta may be less toxic than rHuTNF-alpha in vivo.     

Inbred mice infected with Plasmodium yoelii differ in their antimalarial immunoglobulin isotype response

Antibodies are known to be important in mediating malarial immunity, but the influence of the various immunoglobulin isotypes on parasite elimination is unclear. The purpose of this study was to provide basic information on the induction of isotype expression in genetically different mice during primary malaria. Parasitaemias and the serum antimalarial IgM, IgG1, IgG2, IgG3 and IgA antibody titres measured in a radioimmunoassay were followed in outbred and 11 inbred strains of mice infected with 17XNL Plasmodium yoelii. Severity of infection, as judged by length of infection, peak parasitaemias and death, was found to differ between the strains. All strains developed rapid IgM responses, but only 3/11 inbred strains produced significant antimalarial IgG1 levels during primary infection. All strains produced an IgG2 response, which developed slightly more quickly in strains with the least severe courses of malaria. A large variation in the IgG3 response was noted between strains. In general, IgG3 antibodies were the first IgG-isotype to appear in serum. They were detected as early as day 8 in strains that developed mild infections but were not present until around day 20 in strains with the most severe cases of malaria. Only one strain produced detectable antimalarial IgA antibodies. These results show that different patterns of isotype expression are induced in inbred strains of mice during primary P. yoelii infection.