Handicaps to host defense. Effects of hyperglycemia on C3 and Candida albicans

The hyperglycemic patient remains persistently at risk for infectious complications. Whether ascribable to diabetes mellitus, to the administration of glucocorticoids, or to the infusion of hyperalimentation fluids, hyperglycemia may impair several mechanisms of humoral host defense, including such varied neutrophil functions as adhesion, chemotaxis, and phagocytosis. In addition, binding of glucose to the biochemically active site of the third component of complement C3 inhibits the attachment of this protein to the microbial surface and thereby impairs opsonization. Last, several pathogens frequently encountered in hyperglycemic patients possess unique mechanisms of virulence that flourish in the hyperglycemic environment. Most notable in this regard is the yeast Candida albicans, which expresses a glucose-inducible protein that is structurally and functionally homologous to a complement receptor on mammalian phagocytes. This protein promotes adhesion in the yeast and subverts phagocytosis by the host. Thus, hyperglycemia serves as a central mechanism in the predisposition of hyperglycemic patients to infection.     

Hypophosphaturia impairs the renal defense against metabolic acidosis

It is known that Pi normally provides the major source of non-NH3 urinary buffer and that Pi-buffered renal H+ excretion (titratable acidity, TA) accounts for a large fraction of daily renal net acid excretion (NAE). Whether the presence of luminal non-NH3 buffers is a prerequisite to normal renal regulation of systemic acid-base equilibrium under any conditions has not been investigated. Accordingly, I investigated whether chronic renal regulation of plasma (p) [HCO3] might be impaired under conditions of normophosphatemic hypophosphaturia (NHP) produced by short-term dietary Pi restriction. During a steady-state of HCl-induced acidosis in NaCl-replete NHP dogs (group 1A, N = 6), [HCO3-]p averaged 14.1 +/- 0.6 mEq/liter and arterial (a) [H+] averaged 54 +/- 2 nEq/liter. Substitution K+ 2.5 mEq/kg as neutral Pi for equivalent dietary KCl for 7 to 8 days resulted in significant amelioration of acidosis (delta [HCO3-]p + 2.2 +/- 0.5 mEq/liter, P less than 0.01; delta [H+]a -6 +/- 2 nEq/liter, P less than 0.01) in association with a cumulative increment (sigma delta) in TA excretion (+ 103 mEq, P less than 0.001) and NAE (+ 22 mEq). To investigate whether Pi-induced amelioration of acidosis was related to enhanced urinary buffer capacity, an additional group (group 1B, N = 5) with NHP and chronic HCl acidosis was administered the non-Pi buffer, neutral creatinine (5.0 mmoles/kg daily). As with Pi, acidosis was ameliorated by creatinine administration and sigma delta NAE increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protein-calorie malnutrition inhibits antitumor response to interleukin-2 immunotherapy

The efficacy of systemic interleukin-2 (IL-2) immunotherapy is dependent on a competent host immune response. This study demonstrated that protein-calorie malnutrition (PCM) inhibited the generation of an antitumor response to IL-2. A/J mice received an isocaloric diet of 2.5% or 24% casein 8 weeks before inoculation with C1300 neuroblastoma cells. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T-lymphocyte generation and natural killer cell cytotoxicity. PCM produced a significant reduction in total body weight (p less than 0.001) and serum albumin concentration (p less than 0.001). PCM inhibited generation of cytotoxic T lymphocytes (p less than 0.001), T-lymphocyte response in mixed lymphocyte reaction (p less than 0.001), and in vitro activation of natural killer cell cytotoxicity with IL-2 (p less than 0.001). A second experiment was performed to evaluate whether the in vitro deficits in tumor-specific and natural immunity in the animal model of PCM would diminish the efficacy of systemic high-dose IL-2 (3 x 10(6) units/kg three times daily for 5 days). The mean percent inhibition of C1300 growth with IL-2 was only 15% in mice with PCM compared with 60% in well-nourished mice (p less than 0.01). Median host survival time was greater in well-nourished animals (55 days) compared with animals with PCM (39 days) that received IL-2 (p less than 0.05). These data suggest that nutritional status is a critically important variable in tumoricidal response to systemic IL-2.     

The effects of malnutrition on variables of host defense in the guinea pig

Studies were conducted in young guinea pigs to determine the effects of malnutrition on selected variables of host resistance. Malnutrition was produced differently in two experiments. In the first the quantity of a standard, normal diet was reduced progressively so that test groups were fed 25% less each week over a 4 week period. Control groups were fed ad libitum. In the subsequent experiment, animals were fed defined guinea pig diets containing 5%, 30%, and 60% casein, respectively, which were similar in caloric content, vitamins, and minerals. Measurements of phagocytic bactericidal activity, serum opsonization, serum IgG and C3 levels, and mitogenic response of lymphocytes were made at weekly intervals. Results obtained from both experiments were comparable. There was a significant decline in phagocyte function by the third week in malnourished animals while the numbers of phagocytes per milliliter of peritoneal washings were similar to controls at all time periods. A depression of serum opsonization was observed when animals became moribund even though serum IgG levels remained unchanged. Serum C3 levels in malnourished animals were significantly lower than controls. Mitogenic response of lymphocytes to phytohemagglutinin was 85% lower in the 5% casein group after the third week. These results indicated that a marasmus-like condition and protein malnutrition depress critical functions of resistance.     

Natural host defense mechanisms.

Severe injury, whether the result of a major accident, a large burn, or a complicated surgical operation, often results in sepsis. Under such conditions both specific and nonspecific host defense systems are affected. The individual facets of major concern are chemotaxis, phagocytosis, intracellular killing, complement depletion, and depression of humoral and cellular mediated immunity. The most profound changes occur in cell-mediated immunity. Within a few hours o injury, the number of circulating T cells becomes depleted, concomitantly thoracic duct lymphocytes are markedly reduced. This change is not only quantitative but functional. The clinical impact of these deficient host defense mechanisms lies in the fact that low virulent organisms may become a lethal threat to the injured patient. Currently, investigators are attempting to reverse thse deficiencies through the use of immunotherapy.     

Candida albicans abscess of lung.

Candida albicans lung abscess is a rare entity. We present a case in a patient who suffered from Hodgkin's disease and was receiving immunosuppressive therapy. The patient responded to treatment with 5-fluorocytosine.     

Surgical strategy for spondylodiscitis due to Candida albicans in an immunocompromised host

A 44-year-old woman receiving systemic chemotherapy for cerebellar medulloblastoma developed thoracolumbar spondylodiscitis due to Candida albicans associated with abscesses in the bilateral psoas muscles. As long-term medical therapy with fluconazole was not effective, radical removal of the affected lesions and anterior bone grafting were performed. Corpectomy of the infected vertebra with autologous bone grafting and removal of the psoas muscle were performed via the right transthoracic retroperitoneal approach. Additional posterior instrumentation was not used. Two years after the operation, the patient was doing well, and systemic chemotherapy for medulloblastoma has restarted. Corpectomy with radical resection of surrounding infectious tissues for C. albicans spondylodiscitis in an immunocompromised host should be performed when conservative medical treatment is not successful. Further instrumentation surgery might be necessary to prevent further deformity of the spine as the second surgery.     

Candida albicans spondylodiscitis

Candida spondylodiscitis is a rare complication of a haematogenous dissemination of a candida infection, that usually affects immunocompromised patients. We present a case of a Candida albicans spondylodiscitis in a patient in whom a bacterial origin was suspected because of the antecedent of a Staphylococcus aureus bacteriaemia. After unfavourable evolution with initial antibiotic treatment, the correct diagnosis was reached after culture of the material obtained from surgical debridement. The clinical, diagnostic features, and the literature are reviewed.     

Pericardial constriction caused by Candida albicans.

An uncommon occurrence of constrictive pericarditis caused by Candida albicans and its treatment by successful pericardectomy and epicardectomy are described. For pathogen detection, both cultivation and molecular diagnostics were used. The speed and reliability of molecular diagnostics using polymerase chain reaction make this method a powerful tool for pathogen detection in any clinical specimen.     

Candida albicans myocardial abscess

Cardiac candidosis is a diagnostic and therapeutic challenge. This case report describes persistent candidemia which did not respond to standard therapy and the patient developed a myocardial abscess.     

A systemic study of enhancement of host defense processes against bacterial infection

A sequence of studies over more than two decades has identified a variety of host defense abnormalities that may contribute to clinical infection in high risk and/or badly injured patients. Clearly, animal studies set the stage for our clinical applications and suggest that a variety of so-called non-specific host defense stimulants may indeed correct many of these abnormalities and promote the ultimate control of surgical infections.     

A systemic study of enhancement of host defense processes against bacterial infection

A sequence of studies over more than two decades has identified a variety of host defense abnormalities that may contribute to clinical infection in high risk and/or badly injured patients. Clearly, animal studies set the stage for our clinical applications and suggest that a variety of so-called non-specific host defense stimulants may indeed correct many of these abnormalities and promote the ultimate control of surgical infections. This report is the gist of a paper read by H.C.P. at the 88th Annual Meeting of the Japan Surgical Society, Niigata, Japan, 1988     

The transmission of Candida albicans by cadaveric allografts.

Two transplant patients suffered Candida infections after receiving homografts from a cadaveric donor whose urine culture yielded Candida albicans greater than 100,000 colonies per ml. In both patients the infections became apparent after large doses of methylprednisolone were administered for acute rejection. Flucytosine proved to be inadequate therapy but modified doses of amphotericin B served to eradicate the infection in each case. Donor urine cultures yielding Candida albicans should be interpreted as representing a transmissible infection.     

Alimentary tract colonization by Candida albicans

The usual 20% incidence of rectal colonization by Candida albicans is significantly increased by hospitalization, oral sulfonamides, and systemic antibiotics. Administration of nystatin delays this yeast overgrowth and may well serve as an effective means of prophylaxis against Candida sepsis.Candida can colonize any area of the gastrointestinal tract, but are most prevalent in the mouth and rectum and least populous in the jejunum.Candiduria when possibly due to the intestinal transmucosal persorption of yeast can be eliminated in many cases by the oral administration of an effective antifungal agent, such as nystatin.