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Biomedical subjects

P J Kozinn

Publications and source records attributed to P J Kozinn.

At least 19 recordsLinked to original sources

Do the imidazoles have a role in the management of genitourinary fungal infections?

The imidazoles have demonstrated antifungal activity against a number of fungi that are pathogenic for man. Effective clinical use has been demonstrated in patients with cutaneous and systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcus and systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcus and histoplasmosis. We report our experience with the oral imidazole agent ketoconazole in the management of 8 patients with significant urinary candidiasis as judged by elevated urinary candidal counts (greater than 15,000/ml.). Only 4 of the 8 patients had resolution of candiduria with ketoconazole therapy. Intravenous miconazole, another imidazole, has been available for treatment of systemic and genitourinary fungal infections. Limited success (50 per cent) with intravenous miconazole has been noted in the treatment of systemic candidiasis with urinary involvement. Miconazole also has been used as a systemic and local irrigant in the treatment of bladder and renal candidiasis. Based on these observations and our own studies, we believe that the imidazoles have a limited role in the management of patients with significant fungal involvement of the urinary tract.

Adult↗

Diagnosis of systemic or visceral candidosis.

Although systemic or visceral candidosis can be diagnosed during life, it is usually discovered at autopsy. Early diagnosis is important since treatment with specific antifungal drugs is effective. The diagnosis should rest on all available clinical and laboratory evidence. Mucocutaneous lesions and chorioretinitis are important clinical findings in the presence of predisposing illness and iatrogenic factors. Repeatedly positive blood cultures for Candida in the absence of an indwelling intravenous line and Candida colony counts of 10 000/ml or greater in urine freshly obtained by catheter in the absence of an indwelling Foley catheter are very significant. Similarly significant is recovery of Candida from closed spaces (pleural, peritoneal, joint or subarachnoid). The agar gel diffusion test for Candida antibodies has a sensitivity and specificity of 85% or greater and can confirm the diagnosis in otherwise doubtful cases. The various antibody tests for Candida are not suitable for random screening because of the low prevalence of visceral or systemic candidosis in the general population.

Adult↗

Endotoxemia and hyperbilirubinemia in the neonate.

One hundred twenty-five neonates with varying serum bilirubin levels were tested for endotoxin by the limulus amebocyte lysate (LAL) test. Neither infection nor hemolytic disease was a contributing factor to the bilirubin levels. As the serum bilirubin level rose, positive LAL tests increased in frequency until the LAL test attained 100% at a level of 13 mg/dL. Bilirubin at different concentrations did not elicit positive LAL tests in plasma or normal saline in vitro. The LAL test was positive in urine obtained by suprapubic aspiration in 50% of neonates with positive serum LAL tests. Although bilirubin and endotoxin are cleared independently by hepatic cells with different functions, a striking relationship is evident between the endotoxin and bilirubin levels in the neonate. Immaturity of physiological liver functions in the neonate plays an important role. The LAL test cannot be used as an indicator of Gram-negative sepsis in neonates with unconjugated hyperbilirubinemia.

Bilirubin↗

Amphotericin B as a urologic irrigant in the management of noninvasive candiduria.

High urinary colony counts of Candida may develop in patients with prolonged indwelling bladder catheters, multiple antibiotic usage and compromised host resistance. Serum candidal antibody titers may differentiate candidal colonization or early infection from invasive or disseminated infection. The persistence of marked candiduria in the absence of elevated antibody titers or other manifestations of disseminated infection presents a therapeutic dilemma to the urologist. Should the patient be treated with systemic therapy, that is flucytosine or intravenous amphotericin B, or should he be observed until the signs of systemic or renal infection develop? Amphotericin B may be used as a urological irrigant in the management of noninvasive urinary fungal infection. Of 40 patients with persistent candiduria treated with daily irrigations of amphotericin B via a 3-way indwelling urethral catheter or urethral catheter and suprapubic tube for an average of 6 days 37 (92.5 per cent) demonstrated marked reduction or elimination of the candiduria. None of the patients had an adverse reaction. Amphotericin B also has been used as a urological adjuvant to surgical treatment of candidal infection of the kidney and upper tract. It also has a role in the treatment in candidal urethritis. We believe that the timely use of amphotericin B irrigations may prevent the development of disseminated candidal infection.

Adult↗

Pulmonary candidiasis in infants: clinical, radiologic, and pathologic features.

Although systemic candidiasis is common in hospitalized patients, invasive pulmonary candidiasis is rare and generally considered of secondary importance when found at autopsy. Autopsy records for a 12 year period were reviewed and 15 infants were found in whom systemic candidiasis was considered the primary or a major contributory cause of death. Significant pulmonary involvement was found in 14. There were three characteristic histologic patterns of pulmonary candidiasis: (1) embolic (arterial-invasive) (seven cases); (2) disseminated (capillary-invasive) (four cases); and (3) bronchopulmonary (air space-invasive) (three cases, including one congenital infection). An indwelling vascular catheter or infected cutdown wound was the portal of entry in every case of the embolic form of pulmonary candidiasis. Systemic and pulmonary Candida infections were rarely diagnosed during life. The typical radiographic appearance was progressive air space consolidation, although two infants with the embolic form of pulmonary candidiasis had focal cavitation. In general, there was poor correlation between the radiologic and pathologic findings, and pathologic findings other than pulmonary candidiasis undoubtedly accounted for many of the radiologic abnormalities observed. There were no radiologic findings that could be used to differentiate the three histologic forms of lung involvement in these patients. Small lung nodules, the earliest histologic lesion of pulmonary candidiasis, were not seen in any patient owing to the presence of other lung disease and suboptimal radiographic technique.

Autopsy↗

Flucytosine in the management of genitourinary candidiasis: 5 years of experience.

Candidiasis often is the final insult to the critically ill patient. Flucytosine, an orally administered antifungal agent, was used in the treatment of 225 patients with genitourinary candidiasis. Criteria for treatment included clinical manifestations, high urine colony counts of Candida, serologic findings and in vitro sensitivity of Candida to flucytosine. Infection was eradicated in 212 patients (94 per cent), as determined by clinical and laboratory criteria. The only significant adverse drug effect was reversible agranulocytosis, which ccurred in 2 patients. Thirteen patients (6 per cent) required supplemental therapy with systemic or bladder irrigations of amphotericin B.

Agranulocytosis↗

Incidence and significance of candiduria.

The 100,000 colony count has been used without careful evaluation for the diagnosis of renal candidiasis. Therefore, a prospective study was done on 1,004 urine samples from patients without signs of candidiasis to determine the incidence of candiduria and Candida colony counts. These were compared with colony counts from histologically proved cases of renal candidiasis. The incidence of candiduria varied from a low of 4% in men to a high of 39% in girls during their second week of antibiotic therapy. The overall mean colony count was 1,292 +/- 1,500. The mean colony count in clean-catch urine specimens from six proved cases of renal candidiasis was 23,750 +/- 12,311. The difference in colony counts from proved and unproved cases is statistically significant. Counts greater than 10,000 Candida organisms per milliliter require further investigation.

Adult↗

Efficiency of serologic tests in the diagnosis of systemic candidiasis.

Candida antibody tests for systemic candidiasis were conducted on 53 sera from patients with the disease and 170 sera from control patients by agar gel diffusion, counterimmunoelectrophoresis (CIE), latex agglutination, and whole-cell agglutination. The agar gel diffusion test and CIE had sensitivity, specificity, and efficiency of approximately 90%. The whole-cell agglutination test scored significantly lower, whereas the latex test scored in between. The agar gel diffusion test had the highest reproducibility and the whole-cell agglutination test the lowest in tests of identical sera by six independent laboratories. The agar gel diffusion and CIE tests make significant contributions to the diagnosis of systemic candidiasis.

Agglutination Tests↗

Laboratory evaluation of serological tests for systemic candidiasis: a cooperative study.

Three serological tests for candidiasis, agar gel diffusion (AGD-1), whole cell agglutination (AGGL-1), and latex agglutination (LAT), were evaluated by six laboratories with 100 coded sera. In addition, each of six laboratories performed a test of its choice, either the AGD-2, the AGD-3, the AGGL-2, or one of three counterimmunoelectrophoresis (CEP) methods (CEP-1, CEP-2, and CEP-3). Results are presented by laboratory for a group of 53 "candida-involved" cases (33 proven, 14 presumptive, and 6 probable) and 47 negative controls (41 normal and 6 other disease states). The AGD-1 test produced an overall average of 85.1% positive results in the candida-involved group and 5.0% positives in the control group. The LAT produced an overall average of 89.0% positives in the candida-involved group and 17.4% positives in the controls. The AGGL-1 test produced an overall average of 63.8% positives in the candida-involved group, with 12.3% positives in the controls. In the individual tests, the best performance was shown by the CEP-3 test (92.5% positives in the candida-involved group and 2.1% positives in controls) and the CEP-1 test (88.7% positive in the candida-involved group and no positives in the controls). The tests with the highest sensitivity were the AGGL-2 and CEP-2 (94.3 and 96.2%, respectively). These tests were also the least specific (80.9 and 76.6%, respectively). In the three common tests, the AGD-1 was the most reproducible, whereas the AGGL-1 produced considerable laboratory-to-laboratory variation. Since cell-free extracts of mechanically disrupted C. albicans were used for the LAT and all the AGD and CEP tests, the difference in performance was considered to be mainly due to antigenic composition and the conditions of the test. The results of this study confirm the value of serological tests for the diagnosis of systemic candidiasis, but point out the need for standardized reagents.

Agglutination Tests↗

Evaluation of candida precipitin and agglutinin tests for the diagnosis of systemic candidiasis in burn patients.

Candida agglutinin and precipitin tests were performed on a group of burned patients without evidence of systemic candidiasis to determine whether tests could be used to distinguish between colonization and systemic disease, as has recently been reported. There were considerable numbers of false-positive results using both tests. These false-positive results occurred regardless of the candida colonization status of the patient. We conclude that these tests are of little diagnostic value in burn patients.

Agglutination Tests↗

Endotoxin and bacteria in portal blood.

In order to determine whether endotoxin is normally found in the portal system, intraoperative samples of portal and peripheral blood were drawn from 34 consecutive elective abdominal surgery patients. The limulus lysate test was used to detect endotoxin. Ninety-seven per cent of patients had a positive limulus test in portal blood. Twelve of these patients were tested for portal bacteremia and only one showed growth. Four patients also had systemic endotoxemia. Three of these had liver disease and one had a gram-negative sepsis. This study demonstrates that endotoxin is a normal constituent of portal venous blood in man and does not represent a pathological process. It is suggested that the Kupffer cells of the liver normally protect the systemic circulation from endotoxin, and that endotoxin is present in systemic blood only when liver function is impaired or gram-negative bacteremia is present.

Adenocarcinoma↗

Congenital cutaneous candidiasis.

Three newborn infants are described in whom a generalized maculopapular rash was observed at birth or soon after. The eruption rapidly became vesicular, and in one infant it became bullous, and was followed in each case by extensive desquamation. Candida albicans was demonstrated on direct smear and on culture from the skin vesicles, and evidence of an intrauterine infection with this organism was detected on histologic examination of the placenta in at least two of the cases. Agglutinating antibodies to Candida were present in the sera of all three infants, though these may have reflected transplacental passage of maternal antibody.

Candidiasis, Cutaneous↗

Genitourinary candidiasis: diagnosis and treatment.

Candida in the urine or surgical wound is a potentially lethal pathogen. Management of 82 patients has provided a rationale for the treatment of these infections. Urine colony counts, serologic findings and clinical observations determine therapy. Amphotericin B irrigants are effective for local infections. Disseminated infections require flucytosine and/or intravenous amphotericin B.

Amphotericin B↗

Candida esophagitis: a prospective study of 27 cases.

A prospective study of candida esophagitis was undertaken to determine the spectrum of this disease in a general hospital. During 1 year, in 370 consecutive endoscopies, 27 patients with Candida esophagitis were detected. The diagnosis was established by finding white plaques on endoscopy, yeast organisms on microscopic examination of a direct smear from the plaques, and a serum agglutinin titer of at least 1:160. Of these 27 patients, 14 had esophageal symptoms. Twelve patients were reendoscoped after nystatin or nystatin and flucytosine therapy. Nine patients showed absence of lesions, a negative smear, and disappearance of symptoms. Control patients had no plaques on endoscopy, no yeast organisms on microscopical examination of esophageal brushings, and a positive titer in 4 to 17% of cases. A minimal agglutinin titer of 1:160 was found in 4 to 12% of two additional groups on controls. Absence of titer precluded a diagnosis of Candida esophagitis.

Adolescent↗