The infant food industry and international child health

Declining breast-feeding, with accompanying increased marasmus and diarrhea, has occurred in developing countries because of many factors, including inappropriate health services, new urban life styles, and so forth. The infant food industry must bear a considerable burden of blame as a result of "unethical" advertising. Responses have most recently included various journalistic and legal actions. There is a need for revised roles for the infant food industry, and for mechanisms to monitor intrinsically harmful practices.     

Formal retrospective case review and sudden infant death

A review of 24 consecutive sudden infant deaths was undertaken to evaluate the importance of the various stages in the postmortem assessment of such cases. Death in three cases was caused by obvious trauma. Of the remainder, 16 were attributed to sudden infant death syndrome (SIDS), 4 to accidental asphyxia (identified by death scene examination and/or formal case review) and 1 to a lingual thyroglossal duct cyst. Three (14%) of 21 deaths thought to be SIDS after postmortem examination were attributed to asphyxia following subsequent formal case review.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Adaptive suckling

The process of “adaptive suckling” has evolved appropriate to the needs of different mammal species. It is related to the maturity of the newborn, nutritional requirements, the number of offspring, the need for sensory stimulation, etc. Examples are given of the following species—the echidna, the kangaroo, the blue whale and.the seal. Its relevance to modern man is discussed.     

Factors influencing the acceleration of human factor XIa inactivation by antithrombin III

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.     

Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay

The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory.     

Clinical studies with computer-assisted initial lidocaine therapy

A randomized prospective study compared achievement and maintenance of therapeutic plasma concentrations in patients receiving computer-assisted (CA) initial lidocaine hydrochloride therapy, designed pharmacokinetically to achieve and maintain a chosen plasma concentration, v conventional lidocaine therapy (CT). A separate audit of outcome was also conducted. The CA regimens provided more effective concentrations in the first hour than did CT, 2.65 v 1.5 micrograms/mL average. In the audit, ventricular fibrillation occurred in two of 78 CA v eight of 78 CT patients. Dosage adjustments were required in two CA patients v 33 CT patients. The CA therapy improved therapeutic precision, reduced dosage adjustments, and may have improved safety during initial lidocaine therapy before fitting to plasma concentration data for subsequent feedback. An improved clinical computer program now also fits to plasma concentration data. It is accessed and used routinely by hospitals over an international time-sharing network.     

From guidelines to standards of care for open tibial fractures

IntroductionThe standards for the management of open fractures of the lower limb published by the British Association of Plastic, Reconstructive and Aesthetic surgeons (BAPRAS) and British Orthopaedic Association (BOA) were introduced to improve the treatment received by patients after open injury to the lower limb. These Standards were released after BAPRAS/BOA published Guidelines for the management of open tibial fractures.MethodsWe wished to determine the impact of these Standards upon the surgical management of open tibial fractures by comparing patients admitted to an orthoplastic centre in the 45 months concluding December 2009 (the Guidelines era) with those admitted during 2011 (the Standards era). Surgical procedures required during the first 30 days and 12 months after injury were determined. Cases were divided into ‘directly admitted patients’ (DAP) and ‘transferred patients’ (TP). Standards-era patients were divided further into those who had surgery exclusively at the orthoplastic centre (orthoplastic patients (OPP)) and those transferred after surgery (TASP).ResultsThe number of TP trebled in frequency in the Standards era, 25% of whom were transferred before surgery. Significantly fewer surgical procedures were required for DAP and OPP groups compared with TP (and TASP) groups in both eras (Mann–Whitney U-test, p=0.05). DAP and OPP groups during the Standards era underwent the fewest procedures, with the vast majority of cases treated with two or fewer procedures in the first 12 months (88% and 80%, respectively, compared with 61% in the Guidelines era). In the Guidelines era, 44% of TP cases and in the Standards era 39% of TP and 29% of TASP groups underwent two or fewer procedures.Approximately two-thirds of open tibial fractures managed in our orthoplastic centre were patients transferred after surgery. The greatest impact of the Standards was evident for those who underwent surgery exclusively in the orthoplastic centre, reflecting a more deliberate combined strategy.ConclusionThese findings vindicate the Standards as well as mandating reorganisation and resourcing of orthoplastic services to ensure immediate transfer and early combined surgery. By increasing the capacity to deal with time-dependent initial surgery, the surgical burden that the patient must endure, and which the service must provide, are reduced.