Robert H. Alford

Cell-mediated immunity in Cryptococcosis.

Abstract Cell-mediated immune responses in patients who had recovered from cryptococcosis were compared to those of healthy subjects. Cryptococcal patients were mildly lymphopenic but showed no defect in percentage of thymus-derived lymphocytes. One-third had positive delayed skin test reactions to cryptococcal antigen. Their skin test reactivity to two commonly used noncryptococcal antigens was less intense than healthy control subjects. Strongly positive and specific lymphocyte transformation occurred in the presence of an extract of Cryptococcus neoformans (cryptococcin) in half of the patients. In contrast, few healthy subjects had positive transformation responses to cryptococcin. One patient who was followed sequentially through treatment of cryptococcal meningitis acquired strong cryptococcin reactivity during the course of treatment. Cellular immunologic response to cryptococcin identifies many subjects who have had C. neoformans exposure, and may be of value for assessing immunologic status of patients undergoing therapy. These studies also indicate that most patients with cryptococcosis have a degree of deficiency in cell-mediated response to fungal antigens even when a specific underlying disease process cannot be identified.

Immunologic and clinical improvement of progressive coccidioidomycosis following administration of transfer factor

Abstract Three patients with progressive coccidioidomycosis were given preparations of transfer factor (TF). Adverse reactions to TF were minimal. Following TF administration two of these patients had prolonged clinical remissions in their coccidioidal disease. Cellular immune responses were sequentially evaluated by coccidioidininduced delayed-type skin tests, lymphocyte blast transformation and macrophage inhibition factor production (MIF). These three patients each exhibited different cellular immune patterns before and after TF administration. Two patients converted their coccidioidin skin tests, and one converted lymphocyte transformation response to coccidioidin. Also, TF apparently favorably affected the MIF response in all three patients.

The effect of cirrhosis on the disposition and elimination of clindamycin.

This study assessed the effect of alcoholic cirrhosis in man and of experimental liver injury in rats on the disposition and elimination of clindamycin. In 7 cirrhotics a statistically significant, although modest, prolongation of clindamycin half-life (T1/2β) was observed as compared to values in 7 agematched normal controls (mean ±SD: 4.46±0.93, hr vs 3.42±0.45 hr,P=0.02). This was primarily due to a decrease in clindamycin serum clearance in the cirrhotics, since the volume of distribution of the drug was similar in both groups (P<0.05). Serum protein binding of clindamycin was of the order of 79% and was comparable in both groups (P>0.05). There was a significant correlation between the T1/2β of the drug and both total serum bilirubin and SGOT. The T1/2β of clindamycin was also prolonged in rats with acute hepatic necrosis induced by administration of carbon tetrachloride and those with acute cholestasis caused by common bile duct ligation. These data suggest that liver damage, both chronic and acute, impairs the elimination of clindamycin but that this effect is small.

Atypical Herpesvirus Hominis Type 2 Infection in Uremic Patients Receiving Immunosuppressive Therapy

In four uremic patients (three renal transplant recipients and one with idiopathic thrombocytopenia), painful, initially vesicular lesions developed in the anogenital region while they were receiving immunosuppressive drug therapy. These lesions enlarged, coalesced and ulcerated, presenting a puzzling diagnostic problem. Initial misdiagnoses often resulted in inappropriate antimicrobial therapy. Routine cultures, histologic sections and Tzanck preparations were seldom helpful. The correct diagnosis of herpesvirus hominis (HVH) infection was established within 18 to 48 hours by viral culture of swab or biopsy material. Subsequent identification of isolates as HVH type 2 was confirmed by neutralization kinetics, infectivity titers and ability to plaque in chick embryo cells. Various therapeutic regimens were ineffective. Clinical improvement best correlated with decrease in dosage of immunosuppressive agents.

Candida albicans Infection of Sternum and Costal Cartilages: Combined Operative Treatment and Drug Therapy with 5-Fluorocytosine

Two patients with candidal sternal osteomyelitis have been successfully treated by operative debridement and adjuvant drug therapy with 5-fluorocytosine. One patient had developed postoperative candidal wound infection after sternotomy, and the other acquired candidal sternal osteomyelitis following Candida fungemia. The diagnosis, suggested by culture, was confirmed by identification of Candida pseudohyphae in debrided tissue. Histological confirmation of candidal sternal osteomyelitis indicates the need for operative debridement and specific systemic antifungal therapy. The drug 5-fluorocytosine appears to provide effective oral therapy in this situation.

Staphylococcus aureus bacteremia in hemodialysis patients.

Fifteen male hemodialysis patients developed 21 episodes of S. aureus bacteremia. Infections involving vascular access were responsible for 65% of initial bacteremias. The arteriovenous fistula was the most prevalent type of access used, and thus was responsible for the majority of these illnesses. Phage typing indicated that recurrent episodes were due to reinfection rather than relapse. Complications included endocarditis, osteomyelitis, septic embolism, and pericarditis. One patient died of infectious complications. It is recommended that hemodialysis patients developing bacteremia due to S. aureus receive at least 6 weeks of beta lactamase-resistant antimicrobial therapy.

Transformation of Lymphocytes of Normal and Hospitalized Adults by Candida albicans Extract

Summary Candida extract caused significant tritiated-thymidine uptake (> 5,000 cpm, S/C > 4) in lymphocyte cultures from all normal adults tested. In contrast, in 22% of hospitalized patients, the antigen produced transformation less than any normal subject, and S/C < 4. The difference in candidainduced transformation between normal and hospitalized subjects was statistically significant, while no significant difference in conventional PHA stimulation could be demonstrated. The author thanks Mr. B. B. Cartwright and Miss S. E. Hieny for technical assistance, and Dr. R. Vander Zwaag for performing statistical analyses.

Transformation of Human Lymphocytes by Haemophilus influenzae Somatic and Polysaccharide Antigens

Summary Somatic antigen prepared from either nontypable nonencapulated or type b encapsulated H. influenzae strains is effective in low concentration in causing transformation in vitro of nonfiber-adherent human lymphocytes. Capsular H. influenzae polyribose phosphate is an ineffective stimulant for human lymphocyte transformation in vitro. Significant transformation of peripheral blood lymphocytes from all normal adults tested was effected by the somatic antigen. The author thanks Bruce B. Cartwright and Sara E. Hieny for their excellent technical assistance.

The Effects of Autologous Plasma on Human Lymphocyte Transformation

Summary Autologous plasma was demonstrated both to sustain and inhibit human lymphocyte transformation in vitro. A plasma concentration of less than 1% was unable to adequately sustain PHA-induced transformation. However, by careful adjustments of PHA concentration, a plasma concentration of from 1 to 10% yielded optimum PHA-induced stimulation in the subjects tested. Optimum plasma levels were higher (10–25%) for candida-stimulated and for unstimulated lymphocyte transformation. Sub-optimum stimulation resulted when greater concentrations of plasma than the optimum were employed regardless of the stimulant. Considerable variation occurs between normal individuals in autologous plasma suppression of in vitro lymphocyte transformation.

Perirectal and perineal infections in end-stage renal disease patients

Eight patients with end-stage renal disease (ESRD) who developed bacterial infection of the perirectal area or perineum are reported. The diagnosis was not always straightforward. Bacteremia was seen in 3 of 8 patients and one of these died. Careful examination of the anus, rectum, and perineum should be mandatory in ESRD patients with undiagnosed fever. Treatment consisted of extensive surgical debridement and drainage along with antimicrobial therapy.