Immunologic abnormalities in hemodialysis patients: improvement after pyridoxine therapy.

8 male patients undergoing maintenance hemodialysis were studied to determine the effect of administering supplements of pyridoxine hydrochloride, 50 mg/day for 3-5 weeks, on tests of immune function. In the 3 patients who initially had abnormal nitroblue tetrazolium reduction tests, the values returned to normal with therapy (p less than 0.05). The generation of chemotactic factors from plasma was defective in all evaluated patients and improved after pyridoxine therapy in 4 of 5 patients (p less than 0.01). The lymphocyte subpopulations changed with a rise in the populations of null cells after supplementation with pyridoxine. In addition, lymphocyte transformation in response to mitogens improved in the 3 patients who initially showed low values in these assays. The improvements occurred with pyridoxine therapy even though some patients who responded had no evidence for vitamin B6 deficiency before therapy, as indicated by a normal erythrocyte glumatic-pyruvic transaminase index. We conclude that several parameters of immune function are improved with pyridoxine supplementation. Studies are necessary to establish the minimum daily intake of pyridoxine which will maintain improved values of these tests of immune function in hemodialysis patients.

Prolonged survival with unresected pulmonary metastases.

The cases of 3 selected patients who had prolonged survival with pulmonary metastases that doubled in size yearly are reported. The experience with these patients and another, whose disease rapidly progressed after resection of pulmonary metastases, admonishes that the selection criteria for resection of pulmonary metastases require further refinement.

Daily requirement for pyridoxine supplements in chronic renal failure.

Vitamin B6 deficiency was evaluated in 37 patients with chronic renal failure and in 71 patients undergoing maintenance hemodialysis (HD) or intermittent peritoneal dialysis (PD). Vitamin B6 deficiency was assessed by the in vitro activity of erythrocyte glutamic pyruvic transaminase (EGPT), without (basal) and with (stimulated) the addition of pyridoxal-5-phosphate to the assay, and the EGPT index (stimulated activity ./. basal activity). Basal and stimulated EGPT activities were below normal in the HD patients, and the EGPT index was increased in each group of patients, indicating vitamin B6 deficiency. Supplemental pyridoxine hydrochloride was given to 30 HD patients who received 1.25 to 50 mg/day (37 studies), 6 PD patients who were given 1.25 or 2.5 mg/day (7 studies), and 8 nondialyzed patients with mild to severe renal failure who received 2.5 mg/ day. In all HD patients, 10 or 50 mg/day of pyridoxine hydrochloride rapidly corrected the abnormal EGPT index and maintained normal values; with supplements of 5.0 mg/day or less, the index was often abnormal, particularly in those who were septic or taking pyridoxine antagonists. In PD patients and nondialyzed patients with renal failure, 2.5 mg/day of pyridoxine hydrochloride was inadequate to correct rapidly the abnormal index in all patients. These findings suggest that HD patients should receive 10 mg/day of supplemental pyridoxine hydrochloride (8.2 mg/day pyridoxine). PD patients and patients with chronic renal failure should receive about 5.0 mg/day of supplemental pyridoxine hydrochloride (4.1 mg/day pyridoxine). When sepsis intervenes or vitamin B6 antagonists are taken, 10 mg/day of pyridoxine hydrochloride may be a safer supplement for all patients.

Susceptibility of isolates of Bacteroides to the bactericidal activity of normal human serum.

Seventy-one strains of species from the Bacteroides fragilis group, including 46 isolates of B. fragilis, were tested for susceptibility to the bactericidal effect of serum from healthy subjects. Twenty-seven (38%) of the isolates were killed by serum. Isolates from feces were significantly more sensitive to serum than were isolates from patients with clinical infections. Killing of bacteria required heat-labile serum components and was an exponential function of serum concentration. Among the various species tested, B. fragilis was clearly the most resistant to bactericidal activity of serum. These observations may be important to the understanding of infections caused by the B. fragilis group, which contains the anaerobes of greatest clinical importance.

Introduction of ambulatory medical training in a Veterans Administration hospital.

Planners of postgraduate medical education in the United States have mandated that training programs include experience in continuing patient care in the ambulatory setting. Idiosyncratic administrative features and limitation of resources present relatively unique problems for the development of such programs in Veterans Administration teaching hospitals. The authors describe the implementation of a continuity of care clinic in a highly subspecialized large VA internal medicine training program. Crucially, all residents attend the clinic on the same day. The internal medicine educational program was altered to prevent conflict of the new clinic with other teaching activities. The program has been well received by the involved house staff members and has achieved some of the intended goals.

Survival of anaerobic bacteria in common laboratory diluents.

The survival of six species of anaerobic bacteria was studied in simple or commercially available diluents. Bacteroides fragilis and Fusobacterium nucleatum showed excellent survival in all diluents including distilled water. Fusobacterium mortiferum survived well in all diluents except water and water supplemented with 0.1% gelatain. Clostridium perfringens survived best in phosphate-buffered saline with gelatin. Peptococcus asaccharolyticus required gelatin added to the basic diluent, and Streptococcus intermedius showed excellent survival only in minimal essential medium with gelatin. These diluents could provide effective and economical alternatives to more complex and costly diluents often used in work with anaerobic bacteria.

Acute leukemia following prolonged cytotoxic agent therapy.

1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. Multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.

Aplastic anemia associated with type B viral hepatitis.

Aplastic anemia is a recognized complication of viral hepatitis, but, to our knowledge, no cases associated with type B hepatitis have been described. We report the case of a patient who developed severe aplastic anemia very early in the course of infection with hepatitis B virus.

Polymorphonuclear neutrophil chemotaxis under aerobic and anaerobic conditions.

The motility of human polymorphonuclear neutrophils was studied in vitro under aerobic and anaerobic conditions. Chemotactic factors were generated from plasma with immune complexes or with whole bacteria (Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis). Chemotaxis induced by chemotactic factors generated from immune complexes was identical under both conditions. However, chemotaxis utilizing chemotactic factors generated from bacteria was markedly depressed under anaerobic conditions. Mean random tubemoltility was not significantly different under aerobic and anaerobic conditions. These data indicate that different metabolic pathways may be involved in polymorphonuclear neutrophil movement. Some of these pathways require oxygen (chemotaxis in response to factors generated by bacteria in plasma), whereas others do not (random tube migration and chemotaxis in response to factors generated by immune complexes in plasma). These observations may be important in the induction of inflammatory responses within hypoxic tissues.

An acquired cell-directed inhibitor of neutrophil chemotaxis and hypogammaglobulinemia.

An unusual combination of host defense abnormalities was demonstrated in an adult male with recurrent pulmonary infections due to a variety of microorganisms. Polymorphonuclear neutrophil chemotaxis was defective. Other neutrophil and T-lymphocyte function tests were normal. The patient's serum also showed a severe deficiency of IgG, no detectable IgA, IgM, or IgD, and increased IgE. The chemotactic defect was shown to be due to a cell-directed inhibitor in the patient's serum. The effect of the inhibitor on chemotaxis could be antagonized by factors in normal serum. The chemotaxis defect persisted for several months, but eventually returned to normal.

Comparison of killing of bacteria by guinea pig neutrophils and monocytes.

Guinea pig polymorphonuclear neutrophils (PMN's; harvested from the blood and from peritoneal exudates) and monocytes (harvested from the peritoneal cavity with and without stimulation of an exudate) were compared in their capacities to kill three pyogenic bacteria. All combinations of phagocytes and bacteria required heat-labile opsonic factors. No significant differences in killing of the three organisms were observed between blood and peritoneal PMN's or between stimulated and unstimulated monocytes. PMN's killed Staphylococcus aureus more effectively than monocytes after both 1 and 2 hr of incubation (p less than 0.05). Although PMN's appeared to have greater bactericidal activity against Escherichia coli than did monocytes, this differences was significant only after 2 hr of incubation (p less than 0.05). The killing of Bacteroides fragilis by PMN's and monocytes was identical. These data demonstrate that guinea pig exudates provide suitable models for the study of phagocytosis and killing of bacteria and suggest that the relative bactericidal capacities of phagocytes depend not only on the phagocyte but also on the species of pyogenic bacteria being studied. These observations may have important implications in host defense against serious infections.

Collection of peritoneal exudate cells from small laboratory animals.

A simple method for the collection of peritoneal cells from small laboratory animals is described. Peritoneal exudates were induced by either caseinate or glycogen, and the cells were retrieved through a closed system. The technique permitted repeated studies on individual animals and yielded consistently sterile cell suspensions.

Growth curves of anaerobic bacteria in solid media.

Simple pour plate and spectrophotometric techniques for the evaluation of growth curves of several anaerobic bacteria on solid media are described. Three basic patterns of anaerobic growth were observed. The curves obtained were very reproducible when studied on separate occasions. The curves obtained by spectrophotometric measurement were comparable to those obtained by the pour plate method, especially when a large bacterial inoculum was used. Limitations in the interpretation of the results are discussed. The methods and principles reported could provide the basis for the determination of bacterial growth on solid media using other organisms and different experimental conditions.

In vitro interaction of Bacteroides fragilis with polymorphonuclear leukocytes and serum factors.

The sera and polymorphonuclear leukocytes (PMNs) of healthy human subjects were tested against several isolates of Bacteroides fragilis. All sera killed most of the fecal isolates, but were active aganist only one of the clinical isolates. The degree of killing was directly related to the serum concentration but was independent of the bacterial inoculum within the range of bacterial concentrations studied. The serum bactericidal activity was heat-labile. Engulfment and killing of B. fragilis by PMNs were demonstrated consistently. The opsonim involved in phagocytosis was also heat liable. Calculations involving log-transformed data permitted the quantitative study of the separate and combined effects of serum and PMNs on bacteria which were killed by serum alone. Whereas serum alone usually killed 0.5 log of serum-sensitive bacteria, the addition of PMNs was usually associated with one log further killing. The studies reported here demonstrate the presence of heat-labile serum factors in normal human sera which killed B. fragilis directly and which promote its phagocytosis and killing by PMNs. These observations provide a foundation for investigations into host defense mechanisms against anaerobes.