Elution of glomerular bound antibodies in experimental streptococcal glomerulonephritis.

lmmnunoglobulin G, eluted from glomeruli of rats with streptococcal glomerulonephritis, reacts with type 12 M protein of the streptococcus but not with other streptococcal or renal antigens. Thtrefore, this disease may be madiated by fixation of antigen-antibody complexes consisting of streptococcal M protein and type-specific antibody.

The relationship of antibody-coated bacteria to clinical syndromes as found in unselected populations with bacteriuria.

In selected patients, detection of antibody-coated bacteria (ACB) in voided urine has correlated with upper urinary tract infection. From unselected patients, we studied 350 consecutive urine specimens submitted to the diagnostic laboratory with colony counts greater than or equal to 10(5)/ml. In 19% (55) among 288 specimens selected for final analysis ACB occurred. There were no substantial differences in the occurrence of ACB by age or sex of patients or by species of bacteria. The relationship of ACB to clinical syndromes was: asymptomatic bacteriuria, 15% (27/178); cystitis, 8% (6/75); acute hemorrhagic cystitis, 67% (4/6); prostatitis, 67% (2/3); and acute pyelonephritis, 62% (16/26). Among seven clinical findings, only structural abnormalities of the upper urinary tract correlated with the presence of ACB. Failure of fever and leukocytosis to correlate with ACB probably reflected the presence of other associated primary medical or surgical conditions.

Fever in acute myelogenous leukemia.

Implications and course of fever were evaluated during hospitalization of 24 patients with acute myelogenous leukemia. Forty-five febrile episodes were identified. Fever present at admission was usually associated with a diagnosable and treatable infection; fever shortly after induction was self-limited; and fever during granulocytopenia was more likely to be associated with bacteremia. Bacteremia and pneumonia were the most common types of infection. Only Gram-negative bacteria and Candida were identified as causes of infection during life, with Pseudomonas and Klebsiella the most frequently isolated pathogens. Invasive candidiasis was a major postmortem finding. A delay in initiation of empirical treatment beyond the third day of fever was associated with an increase in mortality as was continuation of treatment for longer than 14 days.

Bacterial arthritis due to beta-hemolytic streptococci of serogroups A, B, C, F, and G. Analysis of 23 cases and a review of the literature.

The clinical features, essential laboratory findings, management, and outcome of all 23 cases of septic arthritis caused by different serogroups of beta-hemolytic streptococcus (BHS) seen at the Stanford Medical Center, Stanford, CA, from July 1, 1985, through October 31, 1996, were reviewed and compared to those found in the literature. Group A streptococci (GAS) accounted for 9 (40%) of our cases; group B (GBS), for 7 (30%); and Group G (GGS), for 7 (30%). No cases were caused by Group C (GCS) or F (GFS) during this period. During the same period, GAS accounted for 66 (33%) of 200 cases of bacteremia due to BHS, GBS, for 98 (49%); GCS, for 12 (6%); GFS, for 4 (2%); and GGS, for 20 (10%). A review of potential risk factors revealed that, with the exception of GGS, male and female patients were almost equally distributed among each of the serogroups. Patients aged 50 years and older comprised 56%-77% of each group. Associated conditions and risk factors were present among most patients (19/23, 83%); autoimmune diseases and a chronic skin wound or trauma were notably present among patients with GAS, while diabetes mellitus and malignancy were more common among patients with GBS. Infected prosthetic implants were present in 7 patients, including 4/7 patients with GGS. All patients had positive cultures of synovial fluid, and 11/23 (49%) had positive blood cultures (GAS, 5/9; GBS, 6/7; and GGS, 0/7). The clinical presentation and hospital course of patients infected with the different serogroups varied. Patients infected with GAS had the most severe disease and those with GGS the least severe. Necrotizing fascitis, shock, DIC, and admission to the intensive care unit were found only among patients infected with GAS. Despite aggressive management with antimicrobial therapy and surgery, 4/23 patients died (3 patients with GAS; 1 with GBS). The isolates from our patients were not available for study; investigations by others of the biology of BHS suggest that the production of 1 or more of the streptococcal pyrogenic exotoxins by isolates of GAS may account for the differences in the severity of disease among our patients with septic arthritis caused by different serogroups of BHS. Although septic arthritis due to BHS is uncommon, such patients provide a valuable model to study features of the host-parasite interaction that may contribute to the observed differences in severity of disease.

Group B streptococcal bacteremia in adults. Five years' experience and a review of the literature.

The importance of group B streptococcus (GBS) as a cause of serious infectious disease among adults is not widely appreciated. In adults, the modes of acquisition and transmission are unknown. Since most hospital-based studies of GBS bacteremia in adults consist of small numbers of patients, the clinical spectrum of disease is not well described. Our retrospective study reviews the clinical features, antimicrobial therapy, and risk factors for mortality of 32 adult patients (18 women and 14 men) with GBS bacteremia and compares the proportion of isolates from the different beta-hemolytic streptococci sero-groups. We found that 39% of isolates from adult blood cultures were group B, a frequency nearly identical to that of group A streptococcal bacteremia. Most (66%) adult patients were more than 50 years old. Primary bacteremia was the most frequent clinical diagnosis, occurring in 7 (22%) of 32 patients. Nonhematologic cancer was the most frequently associated condition (25%). Nineteen percent of the patients had diabetes mellitus. The overall mortality rate was 31% and was significantly associated with increasing age. Our results are compared to those obtained by a review of all 5 previous comparable studies and demonstrate that GBS bacteremia is a serious infection in adults with increased mortality related to advancing age.

Factitious and fraudulent fever.

The task of elucidating the etiology of fever of undertermined origin remains a major undertaking. Factitious fever is uncommonly considered of major importance in the differential diagnosis of fever of undetermined origin although it is a readily identifiable, syndrome and one that is easily excluded one it has been considered. Early identification may reduce the necessity for prlonged, expensive and potentially hazardous hospitalizations for such patients. A retrospective study identified 2.2 per cent (11 of 506) of all patients whose fever on their charts was coded as fever of undetermined origin as having factitious fever. These patients either created factitious fever by manipulation of the thermometer or fraudulent fever by self-induced means. A review of the literature yielded an additional 70 cases in which fever was either the sole factitious sign or part of a larger, more complex factitious illness. Patients were typically young, female and often associated with the medical profession. Patients with factitious fever differ from those with the stereotyped Munchausen's syndrome and may be difficult to recognize. Signs leading to the recognition of this syndrome are emphasized. Since the nature of the psychiatric illness may vary from patient to patient, early discovery may facilitate psychiatric intervention as such patients may be more amenable to therapy.

A sequential study of various modes of skin and umbilical care and the incidence of staphylococcal colonization and infection in the neonate.

The rates of colonization and infection of newborns with coagulase-positive staphylococci were studied during five sequential periods using various modes of skin care in the nursery. Colonization and infection were low during the baseline period when total body bathing with 3% hexachlorophene was employed (period 1), but increased dramatically (80% colonization, 9.5% infection) when hexachlorophene was discontinued and replaced by Ivory Soap baths (period 2). Reinstitution of hexachlorophene (period 3) reduced both colonization and infection, but not to the low levels seen during period 1. A second Ivory Soap period (period 4) resulted in a return to high colonization (77%) and infection (11.5%) rates. During period 5, daily Ivory Soap baths were continued and bacitracin ointment was applied to the umbilical area at least three times daily. Colonization was reduced to 10% and infection to 3.0%. Bacitracin could not be detected in serum in 15 infants studied. Colonization with gram-negative enteric bacilli was highest while using hexachlorophene or Ivory-bacitracin, but no increase in gram-negative infections was seen. Colonization of newborns with non-group A beta-hemolytic streptococci was not influenced predictably with various modes of skin care. The local application of bacitracin is a safe and effective method of controlling staphylococcal colonization and disease for infants in nurseries.

The characteristics of M proteins purified by column chromatography with hydroxyapatite from acid extracts of Streptococcus pyogenes of types 1, 3, 6, 12 and 17.

Purified M proteins were recovered from acid extracts of Streptococcus pyogenes, M-types 1, 3, 6, 12 and 17, by elution from columns of hydroxyapatite of the proteins precipitated with ammonium sulphate. M protein free from non-type-specific antigens was recovered only from M-type 12. Although similar fractions were not recovered from M-types 1, 3, 6 and 17, purified preparations containing a single cross-reactive antigen were obtained. In addition to the M proteins associated with cross-reactive antigens, type-specific antigens that did not stimulate opsonic antibodies were isolated from revealed molecular weights that ranged from 32,000 to 63,000 daltons, total amino acid compositions that were similar, and N-terminal amino acids that were variable.

Outcome measurement in postgraduate year one of graduates from a medical school with a pass/fail grading system.

PURPOSE: To measure the performances of first-year residents who had graduated from a medical school with a pass/fail grading system and to compare the preparedness of these graduates with that of their peers. METHOD: All 169 graduates of Stanford University School of Medicine's classes of 1993 and 1994 were included in this study. First-year program directors rated the performance of each Stanford graduate in 11 areas, compared the graduate's clinical preparedness with that of his or her peer group, and rated the accuracy of the dean's letter in presenting the graduate's capabilities. RESULTS: Responses were obtained for 144 of the 169 graduates (85%). The program directors rated the overall clinical competencies of most of the graduates as "superior" (76%) or "good" (22%); they rated very few as "unsatisfactory" (2%). When the Stanford graduates were compared with their peers, their clinical preparedness was judged "outstanding" (33%), "excellent" (44%), and "good" (20%); very few were judged "poor" (3%). Stratification of programs by either hospital or medical specialty did not reveal significant differences in overall clinical competence. Ninety-one percent of the responses reported that the dean's letters had accurately presented the capabilities of the graduates. CONCLUSION: Graduates from a medical school with a two-interval, pass/fail system successfully matched with strong, highly-sought-after postgraduate training programs, performed in a satisfactory to superior manner, and compared favorably with their peer group.

The relationship of clinical knowledge to months of clinical training among medical students.

PURPOSE: To assess the correlation of the number of months of clinical training with clinical knowledge, as measured by the United States Medical Licensing Examination (USMLE) Step 2. METHOD: The total number of months of clinical training and percentile scores on USMLE Step 2 were determined for 217 Stanford. University School of Medicine graduates from 1992 through 1994. Percentile scores on each subsection of the Medical College Admission Test (MCAT) and the National Board of Medical Examiners Part 1 or USMLE Step 1 (Part 1/Step 1) for the graduates were also determined. For some analyses the graduates were separated into three groups according to the duration of clinical training. The Pearson product-moment correlation coefficient was used to quantify and define the significance of correlations. The Jorickheere-Terpstra nonparametric test was used to assess trends across the three groups. A multiple linear regression model was used to test the effects of confounding variables. RESULTS: The total numbers of clerkship months ranged from 12 to 23; the median was 18. A highly significant correlation was found between increasing months of clinical training and increasing scores on Step 2 (p = .002); a weaker significant correlation was found with scores on Part 1/Step 1 (p = .03). The correlation for Step 2 scores did not diminish appreciably (p = .004) when scores for Part 1/Step 1 and each MCAT subsection were introduced into the regression model. CONCLUSION: A highly significant correlation was found between the amount of clinical training and the acquisition and utilization of clinical knowledge. In the current climate of concerns about the rising costs of medical education, the impulse to solve these concerns by decreasing the amount of medical students' clinical training should be approached with caution.

Characterization of a non-type-specific antigen(s) associated with group A streptococcal type 12 M protein.

The sharing of one and possibly two or more non-type-specific antigens by most strains of groups A, C, and G streptococci is described. With the exception of a single strain of Proteus mirabilis, this antigen(s) was not found among strains of groups B and D streptococci, coagulase-positive staphylococci, Escherichia coli, Pseudomonas sp., and Salmonella sp. The non-type-specific antigen(s) could not be separated from M protein by fractionation with various saturations of ammonium sulfate or by column chromatography with calcium hydroxylapatite even though the latter method allowed the recovery of a fraction of M protein which was free of the cross-reactive antigen(s). The resistance of this non-type-specific antigen(s) to hot acid extraction and its sensitivity to treatment with trypsin differentiate it from the T and R antigens of group A streptococci, both of which are trypsin resistant. Co-precipitation of both type-and non-type-specific antigens occurred with type-specific antiserum and suggested that the type- and non-type-specific antigens represent either different, covalently bonded antigenic determinants on the same protein or different proteins noncovalently linked together.

Production of and sensitivity to colicins among serologically classified strains of Escherichia coli.

A significant proportion of 242 serologically classified strains of Escherichia coli of human origin produced colicins (33%) or were inhibited by one or more of six standard colicins (57%). The most common colicins identified were E1, I, and B; colicins B and V had greatest range of activity. Generally, neither the production of, nor sensitivity to, individual colicins was restricted to strains of a single serogroup. The coexistence of strains of one serogroup that were sensitive to the action of a colicin produced by strains of another serogroup was encountered among 2 of 21 fecal specimens containing strains of multiple serogroups. The production of colicins was not a major determinant in the acquistion of, or subsequent changes in, strains of E. coli in the feces of 10 newborn infants.

Relationship of hemagglutination to other biological properties of serologically classified isolates of Escherichia coli.

The ability of 170 serologically classified strains of Escherichia coli to agglutinate human erythrocytes was examined. Erythrocytes of blood group A were more sensitive indicators of this property than were those of groups B or O. The predominant receptor was shown to be mannose containing; however, an additional receptor was found in two of nine strains studied. Natural mannose-like inhibitors were not found in unconcentrated urine obtained from 12 humans. Isolates from the urine or blood of patients with infections agglutinated erythrocytes significantly more frequently than did isolates from feces. Urine isolates of 10 common serogroups and isolates of less common serogroups did not differ in their ability to agglutinate erythrocytes. Among isolates from the urine of patients with infections, the ability to agglutinate erythrocytes did not correlate with either the serogroup of the strain or the clinical syndrome of the patient. Of the several other biological properties that were examined, only the production of colicins showed a significant association with the ability to agglutinate human erythrocytes.

Recurrent urinary tract infections. Prevention by prophylactic antibiotics after sexual intercourse.

Fourteen patients with chronic or multiple recurrences of infection of the urinary tract have self-administered a single oral dose of one of five antibiotics after sexual intercourse for periods of 19 to 111 months for a total of 761 months. Infections did not occur among 15 of 22 treatment periods. A total of 19 infections occurred while the patients were taking prophylactic medication, significantly less than the total of 90 infections recorded during the 705 months when these patients did not take prophylactic doses of antibiotics. Patients taking nitrofurantoin, a cephalosporin, or nalidixic acid had a significant reduction in the proportion of specimens of urine containing any Gram-negative bacteria. Serious toxic effects were not encountered.

Variation in performance of the serum bactericidal test.

Questionnaires were sent to 37 diagnostic microbiology laboratories to assess their methods for performance of the serum bactericidal test. Of the 28 responding laboratories, 26 utilized the test, with considerable variation among methods. Culture and dilution media included Trypticase soy, Mueller-Hinton, brain heart infusion, Columbia broth, dextrose phosphate, and pooled human serum. Several different schemes for dilution of the test serum were employed, including both micro and macro methods. The greatest variation occurred in the size of the bacterial inoculum, with only eight laboratories having a method for standardization of the inoculum. Other differences included the time of incubation, the method of subculture, and determination of the bactericidal end point. These studies emphasize the need for assessment of the variables in the performance of this test and for the development of a standard method for diagnostic laboratories.

Extraction of streptococcal type 12 M protein by cyanogen bromide.

Conditions for the release of streptococcal type 12 M protein from whole cells by cyanogen bromide are described; they demonstrated that methionine is not essential to the structural arrangements which account for some of its immunological and biological properties. The released M protein was separated from other proteins by column chromatography with hydroxylapatite. The type-specific molecules which reacted with precipitating antibodies were found only in the 0.3 M eluate, formed zones with mobilities less than 12% of that of the dye front on electrophoresis in the standard acrylamide disc gel system, formed at least four bands in sodium dodecyl sulfate-acrylamide disc gels with molecular weights ranging from 12,000 to 23,000, and stimulated the formation of opsonic antibodies in rabbits. Cyanogen bromide provides a highly specific method for the release of M proteins which should prove particularly useful in analyses of structural-functional relationships among different M proteins.

Micromethod for serogrouping Escherichia coli.

A micromethod for serogrouping strains of Escherichia coli is described. The method is accurate, rapid, and economical in terms of time and reagents utilized to perform the test.