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A Zwahlen

Publications and source records attributed to A Zwahlen.

At least 37 records · Page 2Linked to original sources
PubMed1988

[Hyperphosphatemia and transient renal insufficiency following chemotherapy of acute lymphoblastic leukemia].

Acute renal failure during treatment of lymphoblastic malignancies is usually due to drug toxicity or acute uric nephropathy. Observations were recently reported where extreme hyperphosphatemia may represent another pathophysiological mechanism. We describe 2 cases, in 36- and 77-year-old women, with acute lymphoblastic leukemia. Acute renal failure was observed 2 days after cytotoxic treatment. Maximal blood creatinine values were 860 and 550 mumol/l respectively, and for phosphate 6.3 and 7.5 mmol/l. With oral phosphate binders, and after four peritoneal exchanges for the second patient, renal function gradually returned to normal values within 4 weeks. Tumor lysis syndrome with associated hyperphosphatemia is described exclusively in lymphoblastic malignancies and renal failure is probably a consequence of intratubular calcium phosphate precipitation. In this situation prophylactic administration of phosphate binders and attentive monitoring of phosphatemia are necessary.

Acute Kidney Injury↗
PubMed1988

Role of cerebrospinal fluid pleocytosis and Haemophilus influenzae type b capsule on blood brain barrier permeability during experimental meningitis in the rat.

The influence of leukocytes and Haemophilus influenzae type b (Hib) capsule on blood brain barrier permeability (BBBP) to circulating 125I-albumin in normal and leukopenic rats was assessed after intracisternal inoculation of encapsulated (Rd-/b+/02) or unencapsulated (Rd-/b-/02) isogenic strains of Hib. Both normal and leukopenic animals had increased BBBP 18 h after inoculation, with normal rats demonstrating significantly increased BBBP after challenge with the encapsulated strain. Despite cerebrospinal fluid (CSF) pleocytosis in normal rats, CSF bacterial concentrations were not lower. Normal rats cleared unencapsulated Rd-/b-/02 more effectively than leukopenic rats, with BBBP correlating with CSF bacterial density and not leukocyte concentrations. Challenge with heat-killed Rd-/b+/02 resulted in increased BBBP in both normal and leukopenic rats, with greater BBBP at higher bacterial concentrations. The data suggest: (a) significant increases in BBBP occur in the near absence of CSF leukocytes; (b) CSF leukocytes can augment changes in BBBP; (c) type b capsule inhibits host clearance mechanisms within the CSF; and (d) BBBP appears to correlate with bacterial concentrations within the CSF.

Animals↗
PubMed1987

Comparison of immunological methods for diagnosis of pneumococcal pneumonia in biological fluids.

Five immunological tests were evaluated for their ability to detect Streptococcus pneumoniae antigen in serum and urine simultaneously as a means of rapid diagnosis in 40 patients with bacteremic or non-bacteremic pneumococcal pneumonia or pneumonia with other etiologies. Serum and urine were screened in parallel with counterimmunoelectrophoresis (CIE), two commercial latex agglutination kits - the Slidex pneumokit (LA-SPK) and the Bactigen Streptococcus pneumoniae kit (LA-Bac) - the coagglutination Phadebact Pneumococcus test (CoA) and a newly developed enzyme-linked immunosorbent assay (ELISA) containing the immunoglobulin G fraction from rabbit pneumococcal antiserum. The detection rate for accumulated serum in bacteremic patients was 18% for LA-Bac, 24% for CIE, 47% for LA-SPK and CoA and 76% for ELISA, whereas antigenuria was present in only 29% for LA-SPK, 24% for CIE, 19% for CoA, 14% for LA-Bac and 5% for ELISA. Detection by ELISA of pneumococcal antigen in severely ill patients can predict bacteremia and rapidly confirm the diagnosis of pneumococcal pneumonia if sputum and results of blood cultures are not available.

Agglutination Tests↗
PubMed1986

[Hypocalcemia and myelofibrosis: an unrecognized association].

Observation of a case of myelofibrosis with myeloid metaplasia of liver and spleen associated with hypocalcemia led us to investigate whether this association was fortuitous. We retrospectively analyzed the data of 30 patients with myelofibrosis and identified 9 patients with hypocalcemia out of 22 in whom the plasma calcium level corrected for serum protein could be obtained, i.e. a prevalence of hypocalcemia of 41%. The spleen was significantly larger in the patients with hypocalcemia than in those with normal plasma calcium level, suggesting that hypocalcemia was related to the duration of the disease. In 5 patients with hypocalcemia, biological and/or morphological evidence of osteomalacia was found. It is concluded that an association exists between myelofibrosis and hypocalcemia, possibly as a consequence of a disturbed vitamin D metabolism.

Aged↗
PubMed1986

Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats.

The elaboration of type b capsule plays an important role in determining virulence of Haemophilus influenzae but the contribution of lipopolysaccharide to pathogenicity of this organism remains undefined. Using DNA from a virulent type b H. influenzae donor strain and a capsule-deficient recipient (Rd:01), we constructed capsular transformants having lipopolysaccharide characteristics either similar to (strain Rd/b+:01), or different from (strain Rd/b+:02), the recipient strain. These two type b transformants had similar type b capsule and outer membrane proteins. Comparative virulence studies in rats showed that strain Rd/b+:02 was more virulent than Rd/b+01 as assessed by magnitude of bacteraemia, incidence of meningitis and mortality. Similarly, strain Rd/b-:02 exhibited greater pathogenicity in C3-depleted rats than its genetically-related strain Rd:01. We conclude that lipopolysaccharide composition plays a significant role in mediating the potential of H. influenzae to cause invasive infections. In addition, the findings suggest that there is linkage of virulence genes involved in lipopolysaccharide and capsule expression.

Animals↗
PubMed1985

Role of intravascular replication in the pathogenesis of experimental bacteremia due to Haemophilus influenzae type b.

The potential role of extravascular and intravascular replication was studied in initiation of sustained bacteremia in experimental infection due to Haemophilus influenzae type b. When organs and fluid from rats were cultured after intranasal inoculation of the rats with H. influenzae type b, the organism was not recovered from any putative extravascular focus before development of bacteremia. To evaluate the potential contribution of intravascular replication in initiation of bacteremia due to H. influenzae type b, we obtained serial blood cultures after intravenous or intranasal inoculation. Bacterial counts increased exponentially immediately after intravenous and 12-18 hr after intranasal inoculation. Using the same model system, we observed bacteremia due to Streptococcus pneumoniae after intraperitoneal but not intravenous inoculation. After intraperitoneal inoculation, the magnitude of bacteremia in individual rats did not regularly increase exponentially over time. These findings are consistent with extravascular replication leading to bacteremia due to S. pneumoniae and efficient intravascular replication leading to sustained bacteremia due to H. influenzae type b.

Animals↗
PubMed1985

Alteration of the cell wall of Haemophilus influenzae type b by transformation with cloned DNA: association with attenuated virulence.

A virulent strain of Haemophilus influenzae type b was used to construct a lambda library of chromosomal DNA in Charon 4, amplified in Escherichia coli. From this library a recombinant (I-69) phage was isolated that contained a 10.2-kilobase-pair fragment of DNA eliciting H. influenzae transformants whose colonies had a distinctive opaque phenotype. Compared with their H. influenzae parent strains the opaque I-69 transformants had two defined cell wall alterations: one in the lipopolysaccharide (greater mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and one in the outer membrane proteins. The I-69 transformant of virulent type b strain Rd-/b+ had stable expression of type b capsule. In contrast to strain Rd-/b+, the Rd-/b+/I-69 transformant was serum sensitive in vitro and avirulent in vivo in rats. Thus the potential of H. influenzae type b organisms to cause invasive infection can be substantially attenuated by altering the expression of one or more genes that affect the cell wall composition.

Animals↗
PubMed1985

Comparison of radiometric and conventional culture systems in detecting Haemophilus influenzae type b bacteremia in rats.

To compare the efficiency of detecting Haemophilus influenzae type b bacteremia by the BACTEC radiometric system (RS; Johnston Laboratories, Inc., Towson, Md.) and a conventional Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.) blood culture system (TSB), we developed an in vivo model of bacteremia in rats. After intravenous injection of 50 to 200 CFU into adult rats, there was a linear logarithmic increase in CFU per milliliter of rat blood during the first 10 h (r = 0.98), allowing accurate prediction of the level of bacteremia with time. Culture bottles were inoculated with 0.5 ml of blood obtained by cardiac puncture and processed as clinical samples in the microbiology laboratory with our RS and conventional protocols. We found the following. (i) The first detection of bacteremia by RS was similar to that by TSB if a Gram stain of the TSB was done on day 1 and was superior if that smear was omitted (P less than 0.01). (ii) The detection times in both systems were comparable at different magnitudes of bacteremia (10(1) to 10(4) CFU/ml). (iii) Supplementation of inoculated bottles with 2 ml of sterile rat blood interfered with Gram stain detection in TSB but resulted in increased 14CO2 production in RS. (iv) No difference in detection time was found between RS and TSB for four different clinical isolates. These studies show that, in a biologically relevant model, the detection of positive blood cultures for H. influenzae type b by RS was comparable to or better than detection by TSB when blood was processed analogously to clinical specimens.

Animals↗
PubMed1984

Pathogenesis of meningitis: experimental studies on the molecular basis of Haemophilus influenzae infection.

The successful development and implementation of rational strategies for the prevention of bacterial meningitis should be facilitated by acquiring a more detailed knowledge of its pathophysiology. We have used a biologically relevant rat model of meningitis in conjunction with classical microbial genetics and recombinant DNA technology to investigate the molecular basis of Haemophilus influenzae pathogenicity. These studies aim to define how specific bacterial genes mediate the potential of H. influenzae to colonize the nasopharynx, disseminate within the blood stream and invade the central nervous system. By identifying the state or stages in the pathogenic sequence for which the determinant is critical, this approach should also provide insight into the relevant host defense mechanisms which determine resistance or susceptibility. An understanding of the genetic basis of H. influenzae pathogenicity may develop basic knowledge relevant to the treatment and prevention of bacterial meningitis.

Animals↗
PubMed1984

Magnitude of bacteremia and complement activation during Neisseria meningitidis infection: study of two co-primary cases with different clinical presentations.

Two co-primary cases of schoolchildren with acute meningococcal disease due to infection with Neisseria meningitidis serogroup B are described. The first patient presented with septic shock and purpura fulminans, bacteremia greater than 10(5) organisms/ml blood, low C3 and factor B levels and an elevated level of C3d. The second patient had meningitis, negative blood cultures, normal levels of serum complement components but more than 10(4) organisms/ml in CSF. A comparison of the quantitative bacteriology data and complement profiles for these patients suggests that the degree of activation of complement during meningococcemia is directly related to the number of organisms in the blood. This association may determine the different clinical syndromes.

Adolescent↗
PubMed1983

Surface determinants of Haemophilus influenzae pathogenicity: comparative virulence of capsular transformants in normal and complement-depleted rats.

In an assessment of the contribution of different capsular polysaccharides to the pathogenicity of Haemophilus influenzae, the virulence of H influenzae strain Rd and of a series of capsular transformants (types b, c, d, and f) of strain Rd was compared and in normal and complement-depleted rats. After intraperitoneal inoculation, the encapsulated transformants were strikingly more virulent than strain Rd, although their pathogenicity varied; type b was the most virulent, type c the next most virulent, type f less virulent, and type d the least virulent. C3 depletion enhanced the susceptibility of rats to systemic infection but did not influence the relative virulence of the transformants. Comparative studies of clearance showed efficient intravascular survival of type b, c, and f transformants but not of the type d transformant or strain Rd; C3 depletion enhanced the intravascular survival of type d. Further analysis of the capsular transformants revealed differences in the electrophoretic characteristics of their lipopolysaccharides. These studies indicate that elaboration of a unique capsular polysaccharide may not be a sufficient explanation for the greater virulence of H influenzae type b and that lipopolysaccharide may contribute to the mediation of the differential pathogenicity of the various serotypes.

Animals↗
PubMed1983

Participation of complement in host defense against capsule-deficient Haemophilus influenzae.

To investigate the role of complement in immunity to capsule-deficient Haemophilus influenzae, rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule-deficient H. influenzae. Two of them (Rd and U1) did not elaborate type b capsular antigen, whereas the other (S2) elaborated 0.16% of the amount made by its type b parent strain. Depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule-deficient H. influenzae. After intraperitoneal inoculation with strain Rd or U1, C3-depleted rats developed bacteremia, whereas control rats did not; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3-depleted animals. To determine whether the greater virulence of strain S2, as compared with strain Rd or U1, was accounted for by the small amounts of capsular antigen it elaborated, we also compared its relative virulence to that of three genetically closely related capsule-deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen. No difference in virulence was observed among these four variants; all C3-depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates. These studies demonstrate a significant role for complement in host defense mechanisms against capsule-deficient H. influenzae and suggest that interstrain differences of virulence are not attributable to residual elaboration of small amounts of type b capsule.

Animals↗
PubMed1982

Deficient phagocytosis secondary to breakdown of opsonic factors in infected exudates.

Pleural empyema, a clinical entity characterized by the simultaneous presence of large number of PMNLs and viable bacteria, is a biological paradox which has not been fully explained yet. Our preliminary studies suggest that receptor and bactericidal functions of PMNL isolated from purulent exudates, can be close to normal in this condition. Supernatants of these empyemas however have been shown to be low in heat labile opsonic activity and complement hemolytic activity. These observations have been extended by the demonstration of breakdown of IgG, C3 and factor B in infected pleural effusions as opposed to pleural fluids obtained under other conditions. The breakdown of Ig and C3 seems to be enzymatic and to occur, at least for C3, even in the absence of Ca and Mg ions: thus, direct cleavage of C3, possibly by PMNL enzymes, has to be postulated to explain these results. Present work in our laboratory is trying to explore this possibility.

Abscess↗
PubMed1982

Complement-mediated opsonic activity in normal and infected human cerebrospinal fluid: early response during bacterial meningitis.

A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P less than 0.01) and C4 hemolytic activity (P less than 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P less than 0.005). Recovery was also correlated with higher levels of C4 (P less than 0.01) and C3 (P less than 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P less than 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completely.

Adolescent↗