Hypoglycaemia on and after admission in Kenyan children with severe malaria.

We investigated the pathophysiology of hypoglycaemia in severe malaria in African children, especially the potential importance of glycerol as a substrate for gluconeogenesis, and whether substrate limitation contributes to hypoglycaemia in severe disease. Of 171 children with moderate or severe malaria, 16% were hypoglycaemic on admission, while at least 9% of children with severe malaria treated with quinine and a concurrent 4% dextrose infusion had a definite episode of hypoglycaemia after admission. Blood levels of gluconeogenic precursors are as high (alanine and lactate) or higher (glycerol) in those with either hypoglycaemia on or after admission as they are in children never having an episode of hypoglycaemia. Among children with severe malaria, however, those having a definite episode of hypoglycaemia at some stage are more acidotic and have greater evidence of renal impairment than those who are never hypoglycaemic (mean base excess -14.4 vs. -7.2, p < 0.001, mean creatinine 97 vs. 64, p < 0.001 and mean urea 8.1 vs. 5.8, p = 0.03, respectively). These data do not support a role for reduced gluconeogenic substrate supply in the pathogenesis of hypoglycaemia in severe childhood malaria, but do support the hypothesis that gluconeogenesis is impaired. Commonly-used bedside blood glucose monitoring devices may overestimate blood glucose measurements in the normal range, and paradoxically may also seriously overestimate the frequency of hypoglycaemia.

Reimplantation of growth plate chondrocytes into growth plate defects in sheep.

Defects in growth plates due to trauma, infection, or genetic causes can result in bone formation across the defect, bridging the epiphysis and metaphysis, resulting in growth arrest and limb deformation. We have investigated the capacity of implanted chondrocyte cultures to prevent this process. Sheep growth plate chondrocytes were isolated, and after culture at high density produced easily manipulated cartilaginous discs. The tissue was implanted into growth plate defects produced in lambs and the response was assessed histologically. Following implantation, cultures continued to proliferate and maintain a cartilage-like matrix. After 8 to 12 weeks, hypertrophic maturation chondrocyte columnation, and associated endochondral calcification were observed. Culture implantation was always associated with local immune inflammatory reaction, which continued throughout the course of investigation. Cellular survival was variable and resulted in the presence of viable implants as well as residual cartilage matrix devoid of chondrocytes; however, implanted chondrocyte discs always prevented bone bridge formation. These findings encourage the expectation that cultured chondrocytes may provide a useful replacement for the inert interpositional materials currently used in the treatment of growth arrest. The potential of this technique for growth plate replacement, however, requires a more predictable rate of implant survival. The likely reasons for implant loss are discussed.

Swan-Ganz catheter use and mortality of myocardial infarction patients.

Using the 1989 Medicare provider analysis and review (MEDPAR) file, we calculated a 30-day indirectly standardized mortality ratio (SMR) for all "fresh" acute myocardial infarction (AMI) Medicare aged cases (i.e., fresh AMI patients are those who had not reported an AMI in the prior 8 weeks) at 2,900 hospitals, as well as an indirectly standardized procedure ratio (SPR) of Swan-Ganz catheter (SGC) use for these AMI cases at each hospital. Cases at hospitals with higher SGC SPRs also had higher SMRs. This positive association persisted when hospitals were further stratified by their annual volume of fresh AMI cases. We believe that our use of cases as the unit of observation, stratified by the SGC SPR of their hospital, avoids some case selection bias in observational studies directly comparing risk-adjusted mortality of cases with and without SGC.

Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators.

SF2 is a protein factor essential for constitutive pre-mRNA splicing in HeLa cell extracts and also activates proximal alternative 5' splice sites in a concentration-dependent manner. This latter property suggests a role for SF2 in preventing exon skipping, ensuring the accuracy of splicing, and regulating alternative splicing. Human SF2 cDNAs have been isolated and overexpressed in bacteria. Recombinant SF2 is active in splicing and stimulates proximal 5' splice sites. SF2 has a C-terminal region rich in arginine-serine dipeptides, similar to the RS domains of the U1 snRNP 70K polypeptide and the Drosophila alternative splicing regulators transformer, transformer-2, and suppressor-of-white-apricot. Like transformer-2 and 70K, SF2 contains an RNP-type RNA recognition motif.

Herpes simplex oesophagitis in young children.

Herpes simplex oesophagitis is usually associated with debilitated, traumatized or immunologically-compromised hosts. We report here two cases of severe self-limiting oesophagitis in immunologically competent young children that were caused by herpes simplex type 1. This diagnosis should be considered in the differential diagnosis of acute severe pain on swallowing in children for whom oral and pharyngeal pathology have been excluded.

The significance of fat-filled macrophages in the diagnosis of aspiration associated with gastro-oesophageal reflux.

Tracheal aspirates from 46 children were examined for the presence of fat-filled macrophages. They had no history suggestive of gastro-oesophageal reflux. The number of positive results from this group (46%) was compared with the number of positive results (73%) in a group of 40 children with proven gastro-oesophageal reflux. The difference in proportion of positive results between the two groups was statistically significant (P less than 0.05). In addition, subgroups of subjects, negative for gastro-oesophageal reflux and lower respiratory tract disease, were compared with children who had both conditions. A slightly greater difference, although at a similar level of significance, was found. The fact that 42% of subjects without lower respiratory tract disease or gastro-oesophageal reflux had tracheal aspirates positive for fat-filled macrophages would, however, suggest that this test is of limited clinical value and may need better quantitation before it can be recommended for widespread clinical use.

Concomitant IgA nephropathy and cyclical neutropaenia.

A case of concomitant cyclical neutropaenia and IgA nephropathy, a previously undescribed combination is reported. The patient has recurrent aphthous ulceration, and haematuria occurs with these episodes. The diagnosis of cyclical neutropaenia was based on the clinical features and serial peripheral blood studies, and a renal biopsy studied by light, electron and immunofluorescence microscopy in conjunction with the clinical features established the diagnosis of IgA nephropathy. Elevation of serum immunoglobulin, with a disproportionate elevation of IgA was found. The features of this case emphasise the importance of infection as an initiating event in the pathogenesis of IgA nephropathy, and they provide further evidence for the formation of poorly soluble immune complexes as a likely pathogenetic mechanism.

Primary structure of the rat liver asialoglycoprotein receptor. Structural evidence for multiple polypeptide species.

When preparations of rat liver receptor for asialoglycoproteins (rat hepatic lectin, (RHL] are examined by dodecyl sulfate-polyacrylamide gel electrophoresis, multiple polypeptide species are found to be present. The predominant polypeptide has an apparent molecular weight of 41,500 (RHL-1), while two less abundant species appear to be of higher molecular weight (49,000 (RHL-2) and 54,000 (RHL-3]. When the several polypeptides are separated and treated with BrCN, the two minor species are found to share at least one large fragment, while the RHL-1 species gives rise to a completely different set of BrCN peptides. All of the BrCN fragments of the major species and the large common fragment from RHL-2 and RHL-3 have been isolated. These fragments serve as the basis for the complete sequence determination of RHL-1. The complete sequence is 283 residues long, although 20% of the protein as isolated is missing the first 2 residues at the NH2 terminus. The overall arrangement of the polypeptide is similar to the chicken receptor for asialoagalactoglycoproteins; it consists of an NH2-terminal stretch of hydrophilic amino acids, a segment of about 30 uncharged residues, and a COOH-terminal portion which contains three oligosaccharide attachment sites. When the COOH terminus of the rat liver receptor is aligned with the corresponding portions of the chicken liver receptor, the two proteins show 28% identity. Little identity is seen near the NH2 terminus. Sequence homology between residues 50-79 and residues 121-150 of the rat receptor suggests that the additional length of this protein compared with the chicken protein may be due to the presence of a duplicated segment within the rat receptor. The complete sequence of the BrCN fragment common to the two minor species has also been determined; this 101-residue sequence is 53% identical with the COOH-terminal sequence of RHL-1. Since these minor species have a primary structure distinct from RHL-1, there must be at least two genes coding for receptor polypeptides. RHL-2 and RHL-3 may differ in their extent of posttranslational modification.

Open cholecystectomy. A contemporary analysis of 42,474 patients.

OBJECTIVE: This study evaluated, in a large, heterogeneous population, the outcome of open cholecystectomy as it is currently practiced. SUMMARY BACKGROUND AND DATA: Although cholecystectomy has been the gold standard of treatment for cholelithiasis for more than 100 years, it has recently been challenged by the introduction of several new modalities including laparoscopic cholecystectomy. Efforts to define the role of these alternative treatments have been hampered by the lack of contemporary data regarding open cholecystectomy. METHODS: A population-based study was performed examining all open cholecystectomies performed by surgeons in an eastern and western state during a recent 12-month period. Data compiled consisted of a computerized analysis of Uniformed Billing (UB-82) discharge analysis information from all non-Veterans Administration (VA), acute care hospitals in California (Office of Statewide Planning and Development [OSHPD]) and in Maryland (Health Services Cost Review Commission [HSCRC]) between January 1, 1989, and December 31, 1989. This data base was supplemented with a 5% random sample of Medicare UB-82 data from patients who were discharged between October 1, 1988, and September 30, 1989. Patients undergoing cholecystectomy were identified based on diagnosis-related groups (DRG-197 and DRG-198), and then classified by Principal Diagnosis and divided into three clinically homogeneous subgroups: acute cholecystitis, chronic cholecystitis, and complicated cholecystitis. RESULTS: A total of 42,474 patients were analyzed, which represents approximately 8% of all patients undergoing cholecystectomy in the United States in any recent 12-month period. The overall mortality rate was 0.17% and the incidence rate of bile duct injuries was approximately 0.2%. The mortality rate was 0.03% in patients younger than 65 years of age and 0.5% in those older than 65 years of age. Mortality rate, length of hospital stay, and charges were all significantly correlated (p < 0.001) with age, admission status (elective, urgent, or emergent), and disease status. CONCLUSIONS: These data indicate that open cholecystectomy currently is a very safe, effective treatment for cholelithiasis and is being performed with near zero mortality. The ultimate role of laparoscopic cholecystectomy needs to be defined in the context of current and contemporary data regarding open cholecystectomy.

Growth-plate chondrocyte cultures for reimplantation into growth-plate defects in sheep. Characterization of cultures.

Damage to epiphyseal growth plates due to fracture, trauma, or infection can lead to invasion of bone across the cartilage and localized arrest of long-bone growth. The implantation of a viable de novo cartilage plug into such defects may provide the appropriate cartilage presence necessary to inhibit the initial formation of bony bridges across the epiphysis and so maintain the growth potential. De novo cartilage plugs were prepared from ovine growth plates by culturing isolated epiphyseal chondrocytes from fetal lambs. After 14 days of culture, these de novo cartilage discs were composed of chondroitin sulfate, a small amount (5%) of dermatan sulfate, and cartilage-specific collagen. The cellular morphology and the histochemistry resembled resting zones of normal growth-plate cartilage. Those de novo cartilage discs, which had been embedded in gelled Type I collagen, retained their morphology and could be easily manipulated. On the other hand, Type II collagen and a polyuronic acid gauze (Surgicel) were not satisfactory substrates to facilitate subsequent transplantation into growth-plate defects. The use of 5-carboxyfluorescein diacetate succinimidyl ester (CSFE) throughout the cultures of epiphyseal chondrocytes or prolonged incorporation of [3H]-thymidine appeared to label the cells with useful markers for following their fate subsequent to implantation in vivo.

Successful restoration of immunity in the DiGeorge syndrome with fetal thymic epithelial transplant.

A 13-month-old girl presented with right upper lobe pneumonia and hypocalcaemic seizures: investigations showed hypoparathyroidism and impaired cell-mediated immune responses. Other features of the DiGeorge syndrome included hypertelorism, short philtrum of the lip, right-sided aortic arch, and aberrant origin of the left subclavian artery. Successful restoration of the immunodeficiency was achieved by transplantation of fetal thymic epithelium.