Prevalence of Human Papillomavirus in Self-Taken Samples from Screening Nonattenders.

The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self-samples as determined by three HPV assays (the CLART, Onclarity, and Hybrid Capture 2 [HC2] assays) and compare the results with those for physician-taken follow-up samples. The HPV self-sample findings were also compared to the findings for a reference population of 3,347 routinely screened women from the Horizon study, which had been undertaken in the same screening laboratory. Nonattenders had an HPV prevalence of 11.3% as determined by the CLART assay, which was lower than that for women from the Horizon study (18.5%). One-third of the CSi women who tested HPV positive by self-sampling tested HPV negative on the physician-taken follow-up sample. The CLART and Onclarity assays agreed on 64% (95% confidence interval [CI], 60 to 68%) of the HPV-positive self-taken samples. When the HC2 assay results were added into a three-way comparison, the level of agreement decreased to 27% (95% CI, 24 to 29%). Our findings suggest that further validation of HPV assays on self-taken samples is needed for optimal HPV detection and correct clinical management of HPV-positive women.

Treatment of fungal infections with flucytosine.

Treatment with flucytosine of 20 patients with fungal infections gave favorable results in four patients with crytococcal infections, two of four patients with disseminated candidiasis, eight of ten patients with urinary tract infections due to Candida albicans and Torulopsis glabrata, and tow of three patients with miscellaneous infections due to Calbicans. Two patients with crytococcal meningitis and altered host resistance and one patient with an aorto femoral graft infection due to C albicans were treated with flucytosine and smphotericin B. The infection was eradicated in one of the patients with meningitis, and cultures from an infected arterial graft became negative. Adverse side effects of flucytosine included mild leukopenia and thrombocytopenia, a transient increase in alkaline phosphatase and glutamic oxaloacetic transaminase, and nausea and diarrhea.

Nervous system brucellosis: diagnosis and treatment.

We treated six patients with nervous system brucellosis causing polyradiculitis (2 patients), myelopathy (2), encephalitis (1), or meningitis (1). Diagnosis was based on Brucella species cultured from one patient, and a twofold or greater rise in antibody titer after therapy was started in the others. Treatment with trimethoprim-sulfamethoxazole with rifampin (5 patients) or tetracycline (1 patient) produced excellent clinical and laboratory response.

Intracranial tuberculoma: conservative management.

Twenty cases of intracranial tuberculoma were treated by us. A clinical-radiographic syndrome was recognized, consisting of an avascular enhancing mass lesion surrounded by marked edema and associated with relatively less severe clinical manifestations than would have been expected from the size and location of the lesion. This allowed successful medical therapy with three antituberculous drugs for an average of 12 months. Steroids, when used, were beneficial in relieving symptoms of cerebral edema without causing spread of tuberculosis. Medically treated patients had a significantly better functional recovery than those from whom the tuberculoma was excised.

High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV-infected individuals are not associated with increased mortality.

Lymph nodes constitute the major site of HIV replication and of immunological response to HIV. To study the role of cytotoxic and mitotic active CD8(+) lymphocytes in lymph nodes during HIV infection we examined 28 formalin-fixed, paraffin-embedded lymph nodes sampled from 1984 to 1986 from 21 HIV-seropositive patients and seven HIV-negative patients. Eleven of the HIV-positive patients died within 78 months of biopsy time and 10 patients were alive on July 1, 1998. Double immunohistochemical staining procedures were developed to identify CD8(+) cells expressing CD45R0, granzyme B, and Ki-67. A stereological method was used to count the different cell types in the lymph nodes. There were no significant differences in the total cell (nucleated) and CD3(+) cell concentrations between the three groups. However, there were significantly higher concentrations of CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67(+) lymphocytes in the HIV patients compared with the control group. Furthermore, there was a tendency for the HIV-deceased group to have lower levels of CD8(+)granzyme B(+) and CD8(+)Ki-67(+) lymphocyte concentrations compared with the HIV-alive group. Three HIV patients, who progressed to death within 49 months of biopsy time, were among the patients with the lowest concentrations of CD8(+)granzyme B(+) and CD8(+)Ki-67(+) lymphocytes. This finding allowed us to conclude that CD8(+) lymphocytes expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV patients are not related to increased mortality, whereas low concentrations of CD8(+) granzyme B(+) and CD8(+)Ki-67(+) lymphocytes may be associated with poor prognosis.

Treatment of leukemia with partially matched related bone marrow transplantation.

The results of partially matched related donor (PMRD) marrow transplantation for 82 patients with leukemia are reported, including 45 who received two antigen disparate grafts. Following intensive radiochemotherapy, patients received grafts which were partially depleted of T cells by the monoclonal antibody T10B9 and complement. Actuarial probability of engraftment was 86% (95% CI = 78-93%). The median day to engraftment was similar among recipients of grafts disparate at one, two or three antigen loci. The incidence of severe (grades III and IV) acute graft-versus-host disease and extensive chronic graft-versus-host disease was 13% and 6%, respectively. The probability of disease-free survival for the entire cohort of patients is 31% at 3 years. Age < or = 30 years, early or intermediate stage disease and a graft disparate at one or two loci predicted longer disease-free survival in multivariant analysis. Moreover, 47% of patients receiving PMRD grafts disparate at two loci who had both these favorable pretransplant characteristics were alive and free of disease 3 years after transplantation. We believe that the utilization of PMRDs, especially those with two antigen disparate grafts, can extend allogeneic transplantation to additional leukemic patients lacking a histocompatible donor, with acceptable results.

Allogeneic bone marrow transplantation with T cell-depleted partially matched related donors for advanced acute lymphoblastic leukemia in children and adults: a comparative matched cohort study.

Allogeneic BMT provides the best treatment currently available for long-term disease-free survival in patients with recurrent ALL. Historically, partially matched related donors provided the opportunity for treatment to a greater number of patients than matched related donors at the expense of decreased overall survival. In this study we compare the results in recurrent ALL patients transplanted with either HLA identical sibling bone marrow or partially matched related bone marrow. Thirty-two patients with relapsed ALL received partially matched bone marrows from a relative with one to three HLA, A, B and Dr antigen mismatches. Bone marrow was partially T cell-depleted with murine T10B9.1A-31 moAb. Sixteen patients with relapsed ALL received HLA-matched sibling bone marrows. All partially matched patients received additional GVHD prophylaxis with methylprednisolone in addition to anti-CD5 immunotoxin and/or CYA. All matched patients in addition to methylprednisolone received MTX and/or CYA. We observed no difference in disease-free survival between patients transplanted with partially matched bone marrow (median follow-up 1252 days, range 778-2035 days) vs those transplanted with HLA-matched bone marrow (median follow-up 1472 days, range 1165-2800 days; P = 0.48). Median survival for all patients is 38% (95% CI 24-52%) at 6 years. Patients transplanted in remission had a significant increase in disease-free survival when compared to those in relapse (P = 0.007). Our data suggest that partially matched BMTs from related donors are a comparable alternative to fully matched transplants in patients with ALL.

Tuberculous spondylitis in adults.

We treated 107 adults with spinal tuberculosis. The average age was 41.8 years (range, sixteen to seventy-five years). Diagnosis was difficult: bone scans were negative in 35 per cent; gallium scans, negative in 70 per cent; and results of tuberculin skin tests, negative in 14 per cent. Five neurologically impaired patients had no discernible bone lesions when they were first seen but were found to have either intradural or extradural tuberculomas or tuberculous arachnoiditis. Our indications for a spinal operation were neurological impairment, spinal instability, or failure of medical management, and an operation was required in fifty-three of the 107 patients. Anterior decompression and fusion was the surgical procedure of choice. Ninety-four per cent of neurologically impaired patients recovered normal neurological function after anterior decompression; 79 per cent, after non-surgical treatment; and 55 per cent, after laminectomy. Neurological recovery and relief of pain occurred more rapidly in the surgically treated group. Kyphosis did not worsen in any patient, whether treated medically or surgically. There were no organisms that were resistant to isoniazid, rifampin, or ethambutol, and there was neither progression nor reactivation of disease after twelve months of adequate chemotherapy.

[Digital chest x-rays with a selenium detector: a prospective comparison with a conventional film-screen combination]. / Digitale Röntgenthoraxaufnahmen mit einem Selendetektor: prospektiver Vergleich mit einer konventionellen Film-Folien-Kombination.

PURPOSE: To compare a new digital chest radiography system that uses amorphous selenium as the x-ray detector, with conventional radiography for the detection of pathological alterations of the chest. MATERIAL AND METHODS: Two observers analysed pairs of posteroanterior and lateral chest radiographs of 95 patients. One pair of radiographs was obtained with the digital selenium chest radiography system, and the other with conventional film-screen technique. 9 criteria were rated using a 4 point scale. Technical parameters were standardised. Radiation dose was measured in both techniques and compared. RESULTS: A total of 855 criteria were rated. 740 findings were diagnosed in accordance on both techniques (740/855 = 87%). 115 criteria (115/855 = 13%) showed deviations. The mean radiation dose for the selenium detector was 0.02 cGy and for the conventional system 0.11 cGy. CONCLUSION: The exposure of radiation is lower using a selenium x-ray detector compared to conventional film-screen technique in chest radiography. The digital selenium system performs well in a clinical setting, providing visualisation of pathological findings as good as a standard screen-film system.

Spinal brucellosis.

Twenty-one patients with spinal brucellosis were reviewed. The disease is difficult to diagnose, and is often confused with spinal tuberculosis. Our study showed that it was best diagnosed by serology and bacterial culture; radiography and scanning were less helpful in the early stages. After only six weeks' antibiotic treatment, there was a 55% clinical and serological reactivation rate: better results were achieved after at least three months of treatment. The adequacy of treatment was best monitored with repeated agglutination titres, and the duration of treatment proved to be more important than the antibiotic agent itself. Surgical intervention was reserved for biopsy, severe neurological impairment, or for spinal stabilisation.

Enterobacteriaceae meningitis in adults: a review of 20 consecutive cases 1977-97.

Enterobacteriaceae are not a frequent cause of meningitis in adults and are seen mainly in neurosurgical patients and on occasion in elderly and debilitated patients. Consequently, most series studied have been small and selected. In order to obtain a clearer clinical picture, we reviewed 20 consecutive cases of Enterobacteriaceae meningitis admitted to the Department of Infectious Diseases, Rigshospitalet, Copenhagen, during the years 1977-97. They comprised 1.5% of all cases of acute bacterial meningitis admitted to the department. All of the patients were either elderly and/or had 1 or more underlying diseases and predisposing factors. The clinical presentation and cerebrospinal fluid findings were not different from that of acute bacterial meningitis in general. The mortality rate was 40% and correlated with simultaneous bacteraemia. Complications were seen in a further 30% of patients and 25% survived with different sequelae. These high rates may, at least in part, be due to the advanced age and debilitated state of the patients studied. Escherichia coli was the most frequent of the Enterobacteriaceae.

The value of prophylactic antibiotics during the insertion of long-term indwelling silastic right atrial catheters in cancer patients.

Over a 3.5 year period from August 1982 to December 1985, 200 Hickman catheters (Evermed, Medina, WA) were inserted into patients at the King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia. One hundred sixty catheters were placed in patients with malignant disease, many of whom were immunosuppressed at the time of catheter insertion. Seventy of 160 (44%) patients received prophylactic antibiotics and 90 (56%) did not. The mean age of each group was 23 years (range, 2 to 70 years), and the patients in each group were statistically similar in sex, underlying disease, and routine preoperative hematologic and biochemical evaluation. Exit-site wound infections occurred in 50 of 90 (55.5%) patients who did not receive prophylaxis and in 12 of 70 (17%) patients who received prophylaxis (P less than 0.0001). There was no statistically significant difference in the incidence of tunnel and incision site infections. The mean duration of antibiotic prophylaxis was 2.9 days (SD, 1.2 days). Organisms cultured from catheter associated infections, included Staphylococcus epidermidis 36, S. aureus 30, Klebsiella pneumoniae 1, Pseudomonas aeruginosa 3, Escherichia coli 1, and diphtheroids non-CDC-JK 3. Vancomycin was used as antibiotic prophylaxis in 64 patients, Kefzol (Eli Lilly, Indianapolis, IN) in one, oxacillin in three, nafcillin in one, and Septra (Burroughs Wellcome, Research Triangle Park, NC) in one. The data indicate that the use of intravenous antibiotic prophylaxis significantly reduces exit site infection and may reduce both tunnel and incision site infection. Prophylactic antibiotic coverage should be provided to patients during insertion of long-term indwelling right atrial catheters.

Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage-colony-stimulating factor therapy in a patient with Hurler's syndrome undergoing bone marrow transplantation.

Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases.

Acquired immune deficiency syndrome in the Middle East from imported blood.

In Saudi Arabia, a native patient with no known risk factors for the acquired immune deficiency syndrome (AIDS) developed both clinical and laboratory evidence of AIDS 2 years after receiving transfusion of 11 units of blood obtained from a commercial distributor in the United States. This case suggests that a history of transfusions of blood components imported from areas where AIDS is prevalent should be elicited from patients in the Middle East with symptoms and physical findings suggesting AIDS.

Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature.

During a nine-year period, 14 cases of mycobacterial infection (tuberculosis) developed in 403 renal transplant recipients at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, an incidence of 3.5 per cent. The annual incidence of tuberculosis was about 50 times higher than that in the general population. Infection was disseminated in nine (64.3 per cent), pulmonary in four (28.6 per cent), and genitourinary in 1 (7.1 per cent). In one patient tuberculosis was transmitted by the donor's kidney. The clinical manifestations were often ill-defined and not different from that in the normal host. Cultures from all patients grew Mycobacterium tuberculosis; concomitant infection with other organisms was present in five patients (35.7 per cent). Two of 18 patients (group 1) with positive pretransplant tuberculin skin test developed tuberculosis after transplantation (11 per cent), and neither received isoniazid prophylaxis; three of 70 patients (group 2) with negative skin tests developed tuberculosis after transplantation (4.3 per cent). The difference between the two groups was not statistically significant. Review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases. Tuberculosis was disseminated in 38.7 per cent, pulmonary in 40.2 per cent, cutaneous in 12 per cent, and miscellaneous in 9.4 per cent. Atypical mycobacteria were responsible for 29 per cent of disseminated infections, 8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis. Invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis (p less than 0.0001). The mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent (p less than 0.005). These findings (1) confirm the higher incidence of tuberculosis in renal transplant recipients, compared to the general population; (2) suggest that pretransplant skin testing probably has little value in identifying patients at risk; (3) show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis; (4) confirm that the donor kidney may be an important source of infection; and (5) indicate that concomitant infection with other organisms is common.

Brucella endocarditis.

Brucella endocarditis is an underdiagnosed, fatal complication of human brucellosis. Four successfully treated cases of Brucella endocarditis are reported. The development of a new valvar lesion and bulky vegetations seen on echocardiography helped to identify Brucella endocarditis occurring during systemic brucellosis. The aortic valve was affected in all four patients, and in one the mitral valve was also affected. Medical treatment did not cure the patients and all needed valve replacement--for haemodynamic deterioration in three and because a further embolism was feared in one. Antibiotics were continued for six to nine months after operation. There was no early or late mortality and no recurrence after a follow up of 15 months.

Management of anaerobic infections.

Anaerobic infections are reviewed with emphasis on management. Most anaerobic pulmonary infections respond to penicillin G, even when Bacteroides fragilis (penicillin-resistant) is present. Clindamycin is suitable in penicillin-sensitive patients. Intraabdominal infections have a complex flora usually involving anaerobes, especially B. fragilis. It is desirable to use antimicrobial therapy to cover potential pathogens of all types. Surgical drainage and debridement are extremely important considerations. Anaerobic bacteria were found in 72% of 200 patients with female genital tract infections and were the exclusive isolates in 30%. Surgical therapy is primary, but antimicrobial and anticoagulant therapy are also important. A variety of soft-tissue infections involve anaerobes. Surgery is the major therapeutic approach. Anaerobic endocarditis is uncommon but may be difficult to manage. Chloramphenicol is ordinarily the drug of choice for brain abscess. New antimicrobial agents, which are under investigation and are promising, include new penicillins, new cephalosporins, new tetracyclines, and metronidazole.