Safe and effective, prolonged administration of epsilon aminocaproic acid in bleeding from the urinary tract

A total of 9 patients with macroscopic hematuria from various causes, none with evidence of disseminated intravascular coagulation, received low oral, divided doses (approximately 150 mg. per kg. per day) of epsilon aminocaproic acid for up to 21 consecutive days. The hematuria was controlled effectively without overt clinical reactions. Parameters of hepatic and renal function, indicators of muscular damage, were studied in detail in 3 patients. No significant abnormalities were found. The use of small doses of epsilon aminocaproic acid was not accompanied by significant complications and appeared to be effective in special situations for the control of urinary bleeding. This therapy may have indications in a number of urological states accompanied by excessive hematuria.     

Skilled birth attendant competence: an initial assessment in four countries, and implications for the Safe Motherhood movement.

OBJECTIVES: Percentage of deliveries assisted by a skilled birth attendant (SBA) has become a proxy indicator for reducing maternal mortality in developing countries, but there is little data on SBA competence. Our objective was to evaluate the competence of health professionals who typically attend hospital and clinic-based births in Benin, Ecuador, Jamaica, and Rwanda. Methods: We measured competence against World Health Organization's (WHO) Integrated Management of Pregnancy and Childbirth guidelines. To evaluate knowledge, we used a 49-question multiple-choice test covering seven clinical areas. To evaluate skill, we had participants perform five different procedures on anatomical models. The 166 participants came from facilities at all levels of care in their respective countries. Results: On average, providers answered 55.8% of the knowledge questions correctly and performed 48.2% of the skills steps correctly. Scores differed somewhat by country, provider type, and subtopic. Conclusion: A wide gap exists between current evidence-based standards and current levels of provider competence.     

The hospital as an enterprise: management strategies

After introducing the context in which health systems exist in developing as well as in industrialized countries, the author describes the role that hospitals are expected to play as 'enterprises'. The rationale behind such a role is explored and the experience so far available discussed. Evidence from several developing countries suggests caution and tends to discourage radical and indiscriminate introduction of market‐oriented reforms, which international donors seem to be spearheading in Africa's health systems. It is likely, however, that a limited, gradual introduction of selected elements of these reforms (such as some aspects of contracting out, managerial decentralization, the split between purchasing and providing functions) may find its place and eventually have a positive impact on the performance of the health systems. But the 'mystique of markets' must not be allowed to deprive public hospitals of the sense of social utility and of the caring ethos which are essential requisites of a meaningful and effective public health system.     

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.     

Laboratory diagnosis of inherited protein S deficiency

The authors investigated assays for free protein S (ProS) antigen, total ProS antigen, and ProS crossed immunoelectrophoresis (CIEP) in the diagnosis of type 1 inherited ProS deficiency. Accurate measurement of the hemostatically important free ProS required showing that, on each specimen, precipitation of the C4b-binding protein (C4b-BP)/protein S complex (C4b-BP/ProS) by polyethylene glycol-8,000 (PEG) was complete. The authors showed this by doing a ProS CIEP on the same PEG supernate that was used for quantitative measurement of free ProS. The +/- 2 standard deviation (+/- 2 SD) ranges for free ProS were 81-133% for males and 50-130% for females. This striking male-female difference has been reported only twice before. With the use of a graph of values for free ProS versus prothrombin time (PT), patients with inherited ProS deficiency segregated cleanly from normals and from patients on warfarin therapy without ProS deficiency until the PT was greater than 20 seconds. There is overlap of total ProS antigen values between normals and patients with inherited ProS deficiency.     

Twelve novel HLA-B*15 alleles carrying previously observed sequence motifs are placed into B*15 subgroups

Twelve new B*15 alleles are described. All of the known B*15 alleles are divided into subgroups based on serologic assignments and/or nucleotide sequence polymorphisms. These groups might be used as a reference for DNA-based testing at an intermediate (i.e. "serologic") level of resolution.     

Optical anisotropy of a pig tendon under compression*

The proximal region of the superficial digital flexor tendon of pigs passes under the tibiotarsal joint, where it is subjected to compressional and tensional forces. This region was divided into a surface portion (sp), which is in direct contact with the bone and into a deep portion (dp), which is the layer opposite the articulating surface. The purpose of this work was to analyse the distribution and organisation of the collagen bundles and proteoglycans in the extracellular matrix in sp and dp. Toluidine‐blue‐stained sections were analysed under a polarising microscope. Strong basophilia and metachromasia were observed in sp, demonstrating accumulation of proteoglycan in a region bearing compression, but the intensity was reduced the further layers were from the bone. Linear dichroism confirmed that the glycosaminoglycan molecules were disposed predominantly parallel to the longest axis of the collagen fibrils. Birefringence analysis showed a higher molecular order and aggregation of the collagen bundles in areas where the tension was more prominent. The crimp pattern was more regular in dp than in sp, probably as a requirement for tendon stretching. The optical anisotropy exhibited by the collagen bundles also confirmed the helical organisation of the collagen bundles in the tendon. Hyaluronidase digestion caused a decrease in the basophilia, but this was not eliminated, supporting the idea that in the matrix, proteoglycans are not completely available to the enzyme action.     

Neonatal hypothyroidism induces striatal dopaminergic dysfunction

Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied.     

Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-cacchione variant of xeroderma pigmentosum

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two hereditary disorders in which photosensitivity is associated with distinct clinical and cellular phenotypes and results from genetically different defects. We have identified the primary molecular alteration in two patients in whom clinical manifestations strongly reminiscent of a severe form of XP were unexpectedly associated with the CS cellular phenotype and with a defect in the CSB gene. Sequencing of the CSB -coding region in both cDNA and genomic DNA showed that these patients had identical alterations to those in a patient with the clinical features of the classical form of CS. These data, together with fluorescence in situ hybridization analysis, demonstrated that the two siblings with XP as well as the CS patient were homozygous for the same CSB mutated allele, containing a silent C2830T change and a nonsense mutation C2282T converting Arg735 to a stop codon. The finding that the same inactivating mutation underlies different pathological phenotypes indicates that there is no simple correlation between the molecular defect and the clinical features. Therefore, alterations in the CSB gene give rise to the same repair defect at the cellular level but other genetic and/or environmental factors determine the pathological phenotype.     

Early and late paternal contribution to cell division of embryos in a time-lapse imaging incubation system

The objective of this study was to investigate the impact of male age, semen quality and days of ejaculatory abstinence on embryo morphokinetics. A total of 1,220 zygotes obtained from 139 couples in a private in vitro fertilisation centre were analysed. The timing of specific events from the point of insemination, such as timings to pronuclei appearance and fading, to two, three, four, five, six, seven and eight cells and to blastulation were recorded. Multivariate linear regression analysis was used to evaluate the influence of paternal factors on embryo morphokinetic events. Paternal age was positively correlated with delayed cell cleavage and blastulation, and negatively associated with implantation rate, and clinical pregnancy and live–birth chances. The ejaculatory abstinence was inversely correlated with the implantation rate. Inverse relationships were observed between semen parameters (sperm count, progressive sperm motility, total motile sperm count and morphology) and the timing of specific events during embryo development. Sperm morphology was also positively associated with implantation rate and pregnancy and live–birth chances. Increased paternal age and ejaculatory abstinence, and poor semen quality correlate with delayed cell cleavage and blastulation and negatively impact intracytoplasmic sperm injection outcomes.