Adherence of group A streptococci to pharyngeal cells: a role in the pathogenesis of rheumatic fever.

We used an assay in vitro to investigate the possible role of streptococcal adherence to human pharyngeal cells in the pathogenesis of acute rheumatic fever. There was no difference in adherence of rheumatic fever-associated and non-associated strains of group A streptococci to pooled pharyngeal cells of normal people. Likewise, streptococci not associated with rheumatic fever adhered equally well to cells taken from normal people and from patients with rheumatic heart disease. However, the pharyngeal cells of all nine rheumatic heart disease patients tested had increased avidity for adherence for a rheumatic fever-associated strain of streptococcus compared to the pharyngeal cells obtained from age- and sex-matched controls. Increased streptococcal adherence to pharyngeal cells of rheumatic fever-prone patients may play a role in the pathogenesis of rheumatic fever.

Serum inhibitor of C5 fragment-mediated polymorphonuclear leukocyte chemotaxis associated with chronic hemodialysis.

Abnormal granulocyte chemotaxis has been described in chronic hemodialysis patients. In this study, sera from 53 hemodialysis patients were tested for chemotactic inhibitory activity by a modified Boyden technique. Chemotactic inhibitory activity, defined as >20% inhibition of normal granulocyte chemotaxis, was found in 45% of patients. Only sera from patients having undergone >3 mo hemodialysis displayed chemotactic inhibitory activity and retained this inhibitory activity when retested 9 mo later. Four of five patients who had initially undergone <3 mo hemodialysis and lacked serum chemotactic inhibitory activity developed inhibitory activity when tested 9 mo later. Clinical evaluation of patients with serum chemotactic inhibitory activity showed that these patients did not have a significantly increased incidence of infection, although a trend toward decreased mortality during the time of study was observed (P = 0.0721). Serum chemotactic inhibitory activity was heat stable at 56 degrees C for 30 min and concentration dependent. The major inhibitory component was found to have a sedimentation coefficient of 4S by sucrose density gradient centrifugation. The chemotactic inhibitory activity was not precipitated by 30% ammonium sulfate, but was partially precipitated by 50% ammonium sulfate. Inhibitory sera effectively suppressed neutrophil migration in response to chemotactic C5 fragment and Escherichia coli derived chemotactic factor but was least effective in a system mediated by casein. Furthermore, normal neutrophils preincubated in hemodialysis patient sera displayed normal chemotactic responsiveness indicating a lack of cell-directed inhibition. Serum fractions that contained the inhibitor were found to directly act on the chemotactic C5 fragment, reducing its chemotactic activity. This study indicates that a circulating 4S, heat-stable, factor-directed inhibitor of granulocyte chemotaxis is present in the sera of many hemodialysis patients and probably results from the hemodialysis procedure.

Immunologic function in humans before and after hyperthermia and chemotherapy for disseminated malignancy.

Multiple immunologic parameters were studied in three patients prior to and after hyperthermia treatment for disseminated malignancy. Two patients had malignant melanoma and received chemotherapy during the hyperthermia treatment. One had adenocarcinoma of the stomach and received no concomitant chemotherapy. Rapid rosettes as a measure of thymus-derived lymphocytes (T-lymphocytes) were found to increase significantly after therapy (P less than 0.05) both in percentage and absolute numbers. There was no change in the numbers or percentages of other markers for T-lymphocytes or bone marrow-derived B-lymphocytes. Complement profiles revealed a significant decrease in C3 (P less than 0.005) after hyperthermia but no change in levels of other components of the alternate pathway. Antibody-dependent lymphocyte-mediated cytotoxicity and polymorphonuclear cell-mediated antibody-dependent cytotoxicity were also depressed after hyperthermia. No change was observed in immunoglobulin levels with hyperthermia therapy. Results indicated that hyperthermia may favorably alter the immune balance between tumor and host in selected instances.

Routine chest roentgenography is unnecessary in the work-up of stage I and II breast cancer.

PURPOSE: Clinical practice guidelines of many professional societies call for routine staging chest x-rays (SCXR) for all patients with invasive cancer. Given the estimated 157,000 patients annually for whom this recommendation pertains, this screening examination represents a considerable health care expenditure. If it were shown that SCXR rarely changed the management of low-risk subsets of this population, it might be possible to selectively omit this practice from the care of these patients with substantial resultant cost savings. PATIENTS AND METHODS: All patients with clinical stage I and II breast cancer presenting to the Baystate Medical Center from 1989 through 1997 were identified through the Tumor Registry. Their hospital records were reviewed for clinical presentation and documentation of SCXR. RESULTS: One thousand four hundred ninety-four patients were identified with clinical stage I and II disease. SCXR were available for review on 1,003 patients. Only one asymptomatic patient was upstaged to stage IV based on a SCXR. Two patients with primary lung tumors were also identified. These data demonstrate an asymptomatic pulmonary metastasis detection rate of 0. 099% (95% confidence interval, 0.0% to 0.6%). The total charges of SCXR for this group approached $180,000. CONCLUSION: These data demonstrate the low diagnostic yield and high cost of routine SCXR in the management of asymptomatic patients with clinical stage I and stage II breast cancer. Because other studies have shown that SCXR changes neither quality of life nor overall survival, SCXR should be limited to symptomatic patients in whom metastatic disease is suspected.

Bacterial meningitis in the absence of CSF pleocytosis.

Two cases of acute bacterial meningitis occurred with an absent CSF WBC response. To determine the incidence and clinical characteristics of such patients, 50 consecutive cases of meningitis were reviewed retrospectively. In addition to the two initially noted cases, five additional cases were found. In the seven cases, there were six or fewer cells, but bacteria were detected in the CSF. A distinctive clinical and laboratory syndrome emerged. All seven patients were either old or had Hodgkin's disease or severe alcoholism. All patients had evidence of an overwhelming infection with confusion or nuchal rigidity. As compared with the remaining 45 patients with meningitis and CSF pleocytosis, no fever (less than 38 degrees C), a lower peripheral WBC count, and near-normal CSF glucose and protein concentrations were common. Organisms involved were EScherichia coli in three patients, Pneumococcus in three patients, and mixed anaerobes in patient. A fatal outcome ensued in six of seven patients. Despite the correct choice of an antibacterial agent, doses were late and suboptimal for meningitis. This syndrome is surprisingly common in host-defective cases, has an ominous prognosis, and must be treated expectantly with antimicrobial agents that enter the CSF.

Adherent microorganisms on lumenal surfaces of long-term intravenous catheters. Importance of Staphylococcus epidermidis in patients with cancer.

Using electron microscopy, we prospectively evaluated how frequently adherent microorganisms colonized silicone rubber intravenous (Hickman) catheters removed from patients with cancer. Thirteen (87%) of 15 catheters had gram-positive cocci in glycocalyx adherent to the surface of the catheter lumen. Fungal elements or gram-negative bacilli were mixed with the gram-positive cocci in the glycocalyx on the lumens of three catheters. A consistent morphologic form was adherent to, and the same species was recovered from, the corresponding catheter for six of 27 organisms causing septicemia during catheterization: four of five Staphylococcus epidermidis bacteremias and the only Staphylococcus aureus bacteremia, and one of five candidemias. Three of these six septicemias were successfully treated without removal of the catheter. Although adherent organisms, particularly S epidermidis, were likely to be present on the surface of the lumen of long-term, indwelling, silicone intravenous catheters, septicemias potentially related to these organisms occurred infrequently (fewer than two per 1000 days of catheter use), and the suspect septicemias could sometimes be treated without removal of the catheter.

Intermittent, continuous outpatient dobutamine infusion in the management of congestive heart failure.

The use of outpatient dobutamine infusions by a small, portable infusion pump in 3 patients with intractable congestive heart failure (CHF) is described. With this therapy left ventricular function improved and CHF resolved in each. Tolerance to dobutamine was obviated by giving infusions twice weekly. Except for 3 mild infections around the catheter exit site, there have been no complications of this therapy is 58 cumulative patient weeks.

Ionic implantation of silicone chronic venous access devices does not alter thrombotic complications: a double-blinded, randomized clinical trial.

BACKGROUND: Ion implantation of silicone vascular catheters has been shown in preclinical and pilot studies to alter the thrombogenicity of silicone surfaces through the reduced adherence of thrombin. This prospective, randomized double-blinded study was designed to detect differences in function related to thrombotic events between ion-implanted and standard silicone chronic venous access devices (CVAD) placed in patients with cancer who are receiving chemotherapy. METHODS: Patients with nonleukemic malignancies who required venous access for chemotherapy and who were not receiving anticoagulants were randomized to receive standard or ion-implanted CVAD. Postoperative functional assessments of the ease of infusion or aspiration were performed by oncology nurses caring for the patients. RESULTS: Follow-up, available for 100 of 106 randomized patients, showed more episodes of occlusion to aspiration in the ion implantation group (47%) than in the control group (39%) but this difference was not significant. There were no significant differences between the 2 groups in the number of occasions when anticoagulation or local thrombolytic therapy was required nor were there differences in the numbers of infection or deep venous thromboses. CONCLUSIONS: Ion implantation of silicone catheter material does not alter the incidence of local thrombotic complications of CVAD. Although there were no serious complications resulting from this treatment, the use of ion-implanted catheters cannot be recommended on the basis of this trial.

Bacterial colonization of Hemasite access devices.

Vascular access ports (Hemasites) were recovered from patients in whom they had become foci of infection and were examined according to microbiologic and morphologic techniques. All were covered on their extraluminal surfaces by well-developed biofilms consisting of host material and bacteria and their extracellular products. One Hemasite from which Staphylococcus aureus and Streptococcus faecalis were cultured was covered by a biofilm that consisted of coccoid bacterial cells and occasional fungal cells. Another Hemasite from which Proteus mirabilis was cultured was covered by a polymicrobial biofilm consisting of at least six morphologically distinct bacterial types and their extracellular products. This direct observation of the biofilm mode of bacterial growth on these devices suggests that the colonizing organisms will not be completely recovered by routine microbiologic techniques and that bacteria in the biofilm will tend to resist both host clearance mechanisms and antibiotic therapy. Removal of the device, with its accretion of bacterial biofilm, should allow the resolution of the associated infection.

Long-term results and complications of preoperative radiation in the treatment of rectal cancer.

A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.

Resistance to infection of the external eye: the role of tears.

The external eye is continuously exposed to an environment containing potentially pathogenic microorganisms. One of the mechanisms which protects the eye from infection is the tear layer. We review the current knowledge of those antimicrobial substances known to be present in tears and the role they might play in preventing infection. These substances include lysozyme, lactoferrin, beta-lysin, and the antibody-complement system of proteins.

Long-term complications associated with prosthetic repair of incisional hernias.

OBJECTIVE: To determine whether the type of prosthetic material and technique of placement influenced long-term complications after repair of incisional hernias. DESIGN: Retrospective cohort analytic study. SETTING: University-affiliated hospital. PATIENTS: Two hundred patients undergoing open repair of abdominal incisional hernias with prosthetic material between 1985 and 1994. INTERVENTIONS: Four types of prosthetic material were used and placed either as an onlay, underlay, sandwich, or finger interdigitation technique. The materials were monofilamented polypropylene mesh (Marlex, Davol Inc, Cranston, RI), double-filamented mesh (Prolene, Ethicon Inc, Somerville, NJ), expanded polytetrafluroethylene patch (Gore-Tex, WL Gore & Associates, Phoenix, Ariz) or multifilamented polyester mesh (Mersilene, Ethicon Inc). MAIN OUTCOME MEASURES: The incidence of recurrence and complications such as enterocutaneous fistula, bowel obstruction, and infection with each type of material and technique of repair were compared with univariate and multivariate analysis. RESULTS: On univariate analysis, multifilamented polyester mesh had a significantly higher mean number of complications per patient (4.7 vs 1.4-2.3; P<.002), a higher incidence of fistula formation (16% vs 0%-2%; P<.001), a greater number of infections (16% vs 0%-6%; P<.05), and more recurrent hernias (34% vs 10%-14%; P<.05) than the other materials used. The additional mean length of stay to treat complications was also significantly longer (30 vs 3-7 days; P<.001) when polyester mesh was used. The deleterious effect of polyester mesh on long-term complications was confirmed on multiple logistic regression (P=.002). The technique of placement had no influence on outcome. CONCLUSION: Polyester mesh should no longer be used for incisional hernia repair.

Factors related to host recognition of bacterial antigens which cause urinary infection.

Some gram-negative bacteria isolated from the urinary tract have on their surfaces antigens identical to or similar to those of human blood groups A, B, or (H) O. Human isoantibodies to these antigens appear to play some part in the immunologic response to urinary infections. It is postulated from this observation that human isoantibodies A and B persist because they are important segments in resistance to infections rather than reactions to other human tissues (as in transfusions or transplantation). To further assess the relationship between bacterial antigens similar to those of blood groups A or B and host isoantibody response we performed an in-depth study of this relationship in 13 patients with urinary infection of upper or lower tracts. Isoantibody of the immunoglobulin M class appeared to be the antibody which reacted with both bacteria and human erythrocytes. Patients with infections of the upper tracts had proportionately more cross-reacting anti-B antibody than those with lower tract infections, but the amounts of anti-A antibody were roughly equivalent in both types of infection. Response of a given host was genetically predetermined. Some deficiency in host recognition of bacterial antigens was noted since only 4 of 13 patients recognized bacterial A or B antigens while all normals did so. Study of the defined crossreactions between bacterial and blood group antigens offers further opportunities for definition of the genetic components of immunity to urinary infections.

Antibody-coated bacteria in urine of patients with ileal conduit urinary diversion.

The antibody-coated bacteria (ACB) test is a helpful adjunct for differentiating pyelonephritis from cystitis in the intact urinary tract, particularly in female patients. This test was used in patients with ileal conduits and infected urine in an attempt to determine whether bacilluria was of renal or conduit origin. Every patient with infected conduit urine had a positive ACB test even though no patient had clinical stigmas of acute pyelonephritis. In patients with ileal conduits, the ACB test cannot be used alone as an indicator that bacilluria is a cause of symptoms or renal damage.

Use of frozen section analysis in the treatment of basal cell carcinoma.

Frozen section margin verification has been used in the treatment of basal cell carcinoma at our institution for the past 13 years. A review of the last 450 cases has shown frozen section to be most helpful in treating recurrent tumors where microscopic tumor foci extend beyond clinical margins in 45% of cases. Frozen section analysis may be of value in selected patients with primary tumors, but its routine use is not indicated for the majority of these lesions, since complete excision is possible without relying on frozen section in 90% of cases.

The unsatisfactory margin in breast cancer surgery.

BACKGROUND: Surgical margin involvement with breast cancer usually results in obligatory reexcision or mastectomy. While unalterable occult host and pathologic factors may interfere with margin clearance during the initial excision, it is possible that alterations in surgical technique might increase the likelihood of obtaining satisfactory margins. METHODS: Two hundred and thirty-five patients who were candidates for breast conservation therapy were identified for 1991 and 1996 using the Tumor Registry. Margins were defined as "unsatisfactory" if there was microscopic involvement with tumor or the margin was close at initial excisional biopsy and the surgeon opted for reexcision. Multiple logistic regression analyses of factors associated with margin status were performed. RESULTS: One hundred thirty-two (56%) patients had positive or close (unsatisfactory) margins; this rate increased from 51% in 1991 to 59% in 1996. Patients with unsatisfactory margins underwent more procedures (mean 2.0 versus 1.2; P <0.0001) than patients whose margins were satisfactory. The breast conservation rate for patients with unsatisfactory margins was 64% compared with 99% for patients with satisfactory margins. A multiple logistic regression demonstrated that patients with unsatisfactory margins were 67 times more likely to have a mastectomy than patients whose margins were satisfactory after adjusting for other significant factors (P <0.0001). The practice of fine needle aspiration biopsy, orientation of specimen margins by the surgeon, and reexcision of tumor at the first operation were statistically significant technical factors in obtaining satisfactory margins. Significant pathology factors were extensive intraductal component (EIC), lobular or ductal extension, and tumor size. CONCLUSION: These data show that technical factors in the surgical management of breast cancer, as well as biological factors such as EIC, can influence the success of breast conservation.

A prospective analysis of 3525 esophagogastroduodenoscopies performed by surgeons.

BACKGROUND: This study was undertaken to evaluate the safety and efficacy of surgeons performing esophagogastroduodenoscopy (EGD) and to use these results to assess existing credentialing guidelines for surgeons. METHODS: A prospective outcomes study was designed to accept input from members of SAGES. End points were the time taken and rate of success in reaching the duodenum, the frequency of arriving at a diagnosis, and complications of EGD as related to operator experience. RESULTS: Information from a total of 3,525 EGDs was prospectively entered into a database between December 2001 and December 2002. Common indications were abdominal pain/nausea/vomiting (34.8%), gastroesophageal reflux disease (24.9%) and dysphagia (17.4%). The findings were inflammation in 1,895 (53.8%), hiatus hernia in 1,010 (28.7%), nonbleeding ulcer in 462 (13.1%), bleeding ulcer in 59 (1.7%), stricture in 344 (9.8%), and polyp/tumor in 206 (5.8%). Biopsies were obtained in 2080 (59.0%). Concomittant procedures performed were dilation in 253 (7.2%), removal of a foreign body (FB) or removal/insertion of a percutaneous endoscopic gastrostomy tube (PEG) in 190 (5.4%), and polypectomy in 59 (1.7%). The EGD was completed to the duodenum in 3282 patients (93.1%) with a mean procedure time of 9.2 min (range 1-60 min). Examination of the duodenum was not attempted in 231 patients for reasons such as previous gastric surgery ( n = 119), obstruction ( n = 58) or because the EGD was done for FB/PEG removal or PEG placement ( n = 36). Attempted EGD could not be completed in 12 patients (0.3%). The most common complication was hypoxia ( n = 57, 1.6%), which was treated with supplemental oxygen and observation. New bleeding occurred in eight patients and the procedure failed to control bleeding in three others. No complications occurred in 3447 patients (97.8%). Completion rates and major complications were not correlated to experience, but there was a significant association between experience and the time required for completion of the procedure ( p < 0.0001). CONCLUSIONS: This study shows that surgeons can perform EGD with a high degree of success and low morbidity. On the basis of this large prospective study, no minimum number of cases could be proposed for credentialing surgeons to safely perform either diagnostic or therapeutic esophagogastroduodenoscopy.

Neutrophil responses to intravascular pneumococcal sonicate.

Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.

Special studies of the Hickman catheter of a patient with recurrent bacteremia and candidemia.

A patient with acute non-lymphocytic leukemia developed Staphylococcus epidermidis bacteremia and candidemia after maintenance chemotherapy and was treated satisfactorily. He returned 3 months later with abdominal pain due to an abdominal aortic aneurysm. At laparotomy, the aneurysm was found to be infected with Candida albicans. Following surgery, repeated positive blood cultures for C. albicans led to removal of his Hickman catheter. Culture of the catheter tip yielded C. albicans and S. epidermidis. Study of the catheter by scanning and transmission electron microscopy demonstrated yeast-like cells and gram-positive cocci in a biofilm. These studies suggest that the Hickman catheter was the source of the persistent candidemia and that it may have been the origin of the infection of the aneurysm.

Dual lumen catheters for angioaccess in patients with leukemia.

Dual lumen long-term indwelling right atrial catheters have been used to improve venous access in adult patients with leukemia. Twenty-eight such catheters have functioned for 1,895 days in 28 patients over the past eight months at the University of Maryland Hospital. Although insertion of the dual lumen catheter was more technically demanding than insertion of a single lumen catheter, the greater versatility in drug management (e.g., administration of two continuous infusions simultaneously or one continuous infusion leaving one line for platelets, blood, antibiotics or venous sampling) provided by the extra venous portal of entry more than compensated for any increased operative time (average, 58 vs 39 min/insertion). Eight episodes of bacteremia (0.37/100 patient days) occurred in these patients, but only one of these was associated with an exit site infection: the remainder were secondary to infections remote from the catheter. No catheter was removed as a result of these episodes, nor was any removed for ante mortem mechanical failure. The dual lumen catheter is a safe reliable device for providing angioaccess in patients with leukemia and offers substantially greater flexibility than the single lumen catheter.