Biomedical subjects
B Wispelwey
Publications and source records attributed to B Wispelwey.
Pathophysiology of blood-brain barrier alterations during experimental Haemophilus influenzae meningitis.
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Case report: venous thromboembolism in AIDS.
Recently, the authors managed three patients with AIDS and venous thromboembolism. All three were active, ambulatory, and without known risk factors for pulmonary embolism or deep venous thrombosis. One patient had a low titer for IgG anticardiolipin antibody (1:13). Two had low normal values for free protein S, and the third patient had a very low value (5%). Clinicians caring for AIDS patients should be alert to the possibility that venous thromboembolism may complicate HIV infection.
Pentamidine: a review.
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Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor.
The diversity of infectious agents capable of inducing meningitis and blood-brain barrier (BBB) injury suggests the potential for a common host mediator. The inflammatory polypeptides, IL-1 and TNF, were tested in an experimental rat model as candidate mediators for induction of meningitis and BBB injury. Intracisternal challenge of rIL-1 beta into rats induced neutrophil emigration into cerebrospinal fluid (CSF) and significantly increased BBB permeability to systemically administered 125I-BSA as early as 3 h later (P less than 0.05). This injury was reversible, dose dependent and significantly inhibited by prior induction of systemic neutropenia (via intraperitoneal cyclophosphamide) or preincubation of the rIL-1 beta inoculum (50 U) with an IgG monoclonal antibody to rIL-1 beta. Similar kinetics and reversibility of CSF inflammation and BSA permeability were observed using equivalent dose inocula of rIL-1 alpha. rTNF-alpha was less effective as an independent inducer of meningitis or BBB injury over an inoculum range of 10(1) U (0.0016 micrograms/kg)-10(6) U (160 micrograms/kg) when injected intracisternally, but inoculum combinations of low concentrations of rTNF alpha (10(3) U) and rIL-1 beta (0.0005-5.0 U) were synergistic in inducing both meningitis and BBB permeability to systemic 125I-BSA. These data suggest that in situ generation of interleukin-1 within CSF (with or without TNF) is capable of mediating both meningeal inflammation and BBB injury seen in various central nervous system infections.
Pharmacologic interventions aimed at preventing the biologic effects of endotoxin.
In summary, an increased understanding of the pathogenesis and pathophysiology of septic shock has led to the development and evaluation of potential adjunctive therapies. Although several agents show promise in certain experimental settings, definitive recommendations regarding the use of these agents are not yet possible. Although several therapies have shown benefit when the subject receives treatment prior to the onset of sepsis, most have had varying degrees of success following the development of septicemia.
Bacterial meningitis: recent advances in pathophysiology and treatment.
PURPOSE: To review recent advances in the understanding of pathogenic and pathophysiologic mechanisms underlying bacterial meningitis that may lead to the development of adjunctive strategies for treating this disorder. DATA IDENTIFICATION: Studies published from 1975 to 1989 were identified using Index Medicus and by reviewing the bibliographies of identified articles. STUDY SELECTION: We reviewed the experimental and human studies evaluating pathogenesis, pathophysiology, and antimicrobial treatment of bacterial meningitis, as well as those reviews that have contributed to our understanding of meningitis. DATA EXTRACTION: We evaluated the data on the pathogenesis, pathophysiology, and treatment of bacterial meningitis and considered in depth the information from animal models that may have potentially important applications in the treatment of human disease. RESULTS OF DATA SYNTHESIS: Penicillin and ampicillin remain the drugs of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third-generation cephalosporins have revolutionized the treatment of gram-negative bacillary meningitis; one such agent, ceftazidime, is also useful for treating Pseudomonas aeruginosa meningitis. Modification of subarachnoid space inflammation by anti-inflammatory agents may lessen many of the pathophysiologic consequences of bacterial meningitis. A recent study of adjunctive dexamethasone therapy in infants and children with bacterial meningitis showed that the incidence of long-term neurologic sequelae was lower in the corticosteroid group. CONCLUSION: Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease. Additional studies using monoclonal antibodies against specific virulence factors and investigations into the production of inflammatory cytokines in response to bacterial cell products may lead to additional treatments that decrease the high morbidity and mortality in patients with bacterial meningitis.
Pathogenesis and pathophysiology of meningitis.
Advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models. These models have proven to be particularly valuable in experimental bacterial meningitis, focusing on the bacterial virulence factors responsible for the initiation of infections, CNS invasion, and induction of SAS inflammation. Recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors. These cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis (eg. increased BBB permeability, cerebral edema, and increased intracranial pressure). Meningitis due to C. neoformans occurs most commonly in patients with defects in cell-mediated immunity (eg, AIDS), and the depletion of T helper cells in AIDS patients may allow unrestricted cryptococcal growth. Viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites. CNS infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the CNS, primarily through hematogenous dissemination from initial sites of infection. These advances in the pathogenesis and pathophysiology of bacterial, fungal, and viral meningitis may lead to the development of innovative treatment strategies for these disorders.
Bacterial meningitis in adults.
Bacterial meningitis continues to be an important cause of morbidity and mortality despite the availability of effective bactericidal antibiotics. Penicillin or ampicillin remains the drug of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third generation cephalosporins have revolutionized the treatment of gram-negative meningitis. Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease.
Ciprofloxacin in the treatment of Staphylococcus aureus osteomyelitis. A review.
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Pentamidine. A risk-benefit analysis.
With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has greatly increased. This review summarises its pharmacology, its toxicity and clinical experience in the treatment of Pneumocystis carinii pneumonia (PCP). Data are conflicting as to whether pentamidine is more or less effective than cotrimoxazole (trimethoprim-sulfamethoxazole) for the treatment of PCP in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy by many authorities. Hypoglycaemia has been encountered in up to 27% of treatment courses with pentamidine, and nephrotoxicity in 25%. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolised delivery has been evaluated for both therapy and prevention of PCP. Aerosolised pentamidine, on the basis of early clinical results, convenience and low toxicity, may become the drug of choice for prevention of PCP in individuals at high risk. However, its role in the treatment of PCP remains to be defined. Preliminary studies suggest that it is effective, but the data are insufficient to support its use outside of clinical trials.