Early Cretaceous biogeographic and oceanographic synthesis of Leg 123 (off Northwestern Australia)

Biogeographic observations made by Leg 123 shipboard paleontologists for Lower Cretaceous nannofossils, foraminifers, radiolarians, belemnites, and inoceramids are combined in this chapter to evaluate the paleoceanographic history of the northwestern Australian margin and adjacent basins. Each fossil group is characterized at specific intervals of Cretaceous time and compared with data from Tethyan and Southern Hemisphere high-latitude localities. Special attention is given to the biogeographic observations made for the Falkland Plateau (DSDP Legs 36 and 71) and the Weddell Sea (ODP Leg 113). Both areas have yielded valuable Lower Cretaceous fossil records of the circumantarctic high latitudes. In general, the Neocomian fossil record from DSDP and ODP sites off northwestern Australia has important southern high-latitude affinities and weak Tethyan influence. The same is true for the pelagic lithofacies: radiolarian chert and/or nannofossil limestone, dominant in the Tethyan Lower Cretaceous, are minor lithologies in the Exmouth-Argo sites. These observations, together with the young age of the Argo crust and plate tectonic considerations, suggest that the Argo Basin was not part of the Tethys Realm. The biogeography of the Neocomian radiolarian and nannofossil assemblages suggests opening of a seaway during the Berriasian that connected the circumantarctic area with the Argo Basin, which resulted in the influx of southern high-latitude waters. This conclusion constrains the initial fit and break-up history of Gondwana. Our results favor the loose fit of the western Australian margin with southeast India by Ricou et al. (1990), which accounts for a deeper water connection with the Weddell-Mozambique basins via drowned marginal plateaus as early as the Berriasian. In fits of the du Toit-type (1937), India would remain attached to Antarctica, at least until the late Valanginian, making such a connection impossible. After the Barremian, increasing Tethyan influence is evident in all fossil groups, although southern high-latitude taxa are still present. Biogeographic domains, such as the southern extension of Nannoconus and Ticinella suggest paleolatitudes of about 50°S for the Exmouth-Argo area. Alternatively, if paleolatitudes of about 35° are accepted, these biogeographic limits were displaced northward at least 15° along Australia in comparison to the southern Atlantic. In this case, the proto-circumantarctic current was deflected northward into an eastern boundary current off Australia and carried circumantarctic cold water into the middle latitudes. Late Aptian/early Albian time is characterized by mixing of Tethyan and southern faunal elements and a significant gradient in Albian surface-water temperatures over 10° latitude along the Australian margin, as indicated by planktonic foraminifers. Both phenomena may be indicative of convergence of temperate and antarctic waters near the Australian margin. High fertility conditions, reflected by radiolarian cherts, are suggestive of coastal upwelling during that time

Controversies in the Use of Passive Immunotherapy for Bacterial Infections in the Critically Ill Patient

Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitively established. Specific preparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available cross-protective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pool

Comparative imipenem treatment of Staphylococcus aureus endocarditis in the rat

The efficacy of imipenem alone or in association with gentamicin against Staphylococcus aureus experimental endocarditis was compared to the efficacy of cloxacillin alone or in association with gentamicin. Parenteral treatment was started 24 h after intravenous bacterial challenge of rats with catheter-induced aortic valve vegetations. The cloxacillin MIC and MBC for Staph. aureus were 0.125 and 32 mg/l and the imipenem MIC and MBC 0.008 and 8 mg/l, respectively. In-vitro killing curves showed a synergistic effect between cloxacillin and gentamicin, and an additive effect between imipenem and gentamicin. Only large doses of cloxacillin (400 mg/kg tid) (producing serum levels above those obtained after intravenous injection of 2 g in man) achieved results comparable to those of imipenem 80 mg/kg tid (producing serum levels similar to those obtained after an intravenous dose of 750 mg in man) in reducing the bacterial numbers in vegetations after 3 and 5 days of treatment. There was a significantly greater reduction of bacterial numbers in vegetations after treatment with the association of cloxacillin and gentamicin than with cloxacillin alone. In contrast, the addition of gentamicin to imipenem did not improve significantly the results of treatment with imipenem alone, but imipenem alone was as good as the combination cloxacillin and gentamicin after 5 days of treatment. We conclude that imipenem is a highly bactericidal drug in this animal model, worth considering for clinical trials in the treatment of Staph. aureus infection

Comparative study of imipenem in severe infections

Forty patients with severe bacterial infections due to micro-organisms known or presumed to be sensitive to both study antibiotics, were randomized to receive either imipenem with cilastatin, 500 mg/500 mg iv tid (20 patients), or cefotaxime, 2 g iv tid (20 patients). The types of infections observed were equally distributed between the 2 groups, and consisted of 18 complicated urinary tract infections, 9 pneumonia, 7 bone and soft tissue infections, 4 septicaemia of unknown origin and 2 intravenous-catheter-related septicaemia. In the imipenem group, 12 patients were bacteraemic, compared to 10 in the cefotaxime group. The micro-organisms observed were evenly distributed with Escherichia coli (22 cases) and Klebsiella pneumoniae (6 cases) being the most frequent. Sixteen patients were cured in the imipenem group and 15 in the cefotaxime group, while 2 and 2 improved, 2 and 1 relapsed and 0 and 2 did not respond to the therapy, respectively. In the imipenem group, no clinical side effects were observed while 5 patients had mild reactions in the cefotaxime group (2 fever, 1 skin rash, 1 oral candidiasis and 1 diarrhoea). Imipenem thus appeared as effective and well tolerated as cefotaxime in the treatment of severely infected patient

Controversies in the use of passive immunotherapy for bacterial infections in the critically ill patient

Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitively established. Specific preparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available cross-protective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pools

Pathogenesis and Potential Strategies for Prevention and Treatment of Septic Shock: An Update

Septic shock is mediated by complex interactions of cells, cytokines, and humoral pathways. Clinical therapeutic strategies aimed at inhibiting selected pathways have been efficacious in subsets of patients. Experimental studies focusing on the activities of single cytokines have contributed to the understanding of the complex pathophysiology of septic shock. More precise delineation of the roles of each mechanism contributing to pathogenesis will permit the identification of subsets of patients who might benefit from particular therapeutic strategies and will guide the development of additional approaches to prevention and treatmen

Gene identification for the cblD defect of vitamin B12 metabolism

Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified. Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis. Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence. Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder

Antibodies to Lipopolysaccharides after Immunization of Humans with the Rough Mutant Escherichia coli J5

To investigate whether immunization with Escherichia coli J5 boiled cells induces antibodies directed at deep core structures, antibodies against JS lipopolysaccharide (LPS), Re LPSt and Iipid A were measured in the serum of 70 volunteers before and 2 weeks after immunization. To improve the sensitivity and the specificity ofELISAt complexes of core LPS with high-density lipoproteins were used instead of free core LPS as antigens. A median three-fold increase in antibodies directed against J5 LPS was observed, but no significant increase in the antibodies against Re LPS or lipid A was found. Since JS antiserum did not react with several smooth LPS or with Re LPS and lipid At cross-reactivity could not be demonstrated. Thus, immunization of volunteers with E. coli J5 produced a modest specific antibody response against J5 LPS. The mechanism of protection previously observed with J5 antiserum remains unclea