Delayed tuberculosis diagnosis and tuberculosis transmission.

SETTING: Tuberculosis (TB) patients and their close contacts reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. OBJECTIVES: A recent prospective study found that 49% of pulmonary TB patients had total treatment delays > or = 90 days. This cohort was analyzed to determine the association between total treatment delay and TB transmission. DESIGN: TB patient data were collected as part of a prospective cohort study; contact data were collected from local health departments. RESULTS: Close contacts of 54 US-born patients (n = 310) and those of 70 foreign-born cases (n = 393) received tuberculin skin tests (TSTs). Among contacts of US-born patients with a total treatment delay of > or = 90 days, 40% had positive TSTs vs. 24% contacts of patients with shorter delays (aOR 2.34; P = 0.03). Other patient factors associated with TST positivity among contacts of US-born cases were black race (aOR 3.03; P = 0.05), sputum smear positive for AFB (aOR 3.29; P = 0.01) and chest radiograph with cavitation (aOR 3.11; P = 0.01). No associations were observed between foreign-born patients and risk of TST positivity among their contacts. CONCLUSION: Among US-born patients, delay in TB diagnosis is associated with greater transmission of infection to contacts and could be used independently of other index patient factors to identify contacts at greatest risk of TB infection.

Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.

BACKGROUND: Tamoxifen is advantageous in treating all stages of breast cancer. However, studies have suggested that incidence and severity of endometrial cancer increase in women treated with tamoxifen. PURPOSE: We compared rates of endometrial and other cancers in tamoxifen- and non-tamoxifen-treated patients and described the pathologic characteristics of the endometrial cancers. METHODS: Data were analyzed on 2843 patients with node-negative, estrogen receptor-positive, invasive breast cancer randomly assigned to placebo or tamoxifen (20 mg/d) and on 1220 tamoxifen-treated patients registered in NSABP B-14 subsequent to randomization. Average time on study is 8 years for randomly assigned patients and 5 years for registered patients. RESULTS: The incidence rates of liver, gastrointestinal, urinary tract, and nonuterine genital tumors were not increased by tamoxifen treatment. Twenty-five endometrial cancers were originally reported, one of which was reclassified after subsequent review. Two cases occurred in the placebo group in patients whose medical status subsequent to random assignment had required tamoxifen treatment. Twenty-three occurred in the tamoxifen groups. Twenty-one of the 24 originally reported endometrial cancers were FIGO stage 1; 18 of 23 gradable cases were of good to moderate histologic grade. Four tamoxifen-treated women died of uterine cancer. The average annual hazard rate of endometrial cancer as a first event within the first 5 years of follow-up in the randomized, tamoxifen-treated group was 1.2/1000 patient-years; the cumulative hazard rate was 6.3/1000. Findings for the registered, tamoxifen-treated group were similar. Including all originally reported endometrial cancers, the annual hazard rate through all follow-up was 0.2/1000 in the placebo group and 1.6/1000 in the randomized, tamoxifen-treated group; the relative risk of endometrial cancer for the latter versus the former group was 7.5. Again for the latter group, using population-based rates of endometrial cancer from SEER data and information from another NSABP (B-06) trial, relative risks were 2.2 and 2.3, respectively. The 5-year cumulative hazard rate for disease-free survival in the randomized tamoxifen group was 38% less than that in the placebo group. Some data in this paper were provided by an investigator who submitted fraudulent data to the NSABP [see the "News" section]; therefore, the reader must read the entire text including Table 10 and the Editor's notes. In brief, data on 182 of the 2843 randomly assigned patients and 37 of the 1220 registered patients were provided by the investigator in question. After review, 24 of the 182 records showed falsification, all involving characteristics of patients prior to random assignment. Of the 37 registered-patient records, 8 showed falsification. CONCLUSIONS: Risk of endometrial cancer increases following tamoxifen therapy for invasive breast cancer; however, net benefit greatly outweighs risk. Endometrial cancers occurring after tamoxifen therapy do not appear to be of a different type with a worse prognosis than are such tumors in non-tamoxifen-treated patients. IMPLICATIONS: Tamoxifen treatment for breast cancer should continue. In addition, the relative risk of endometrial cancer observed in B-14 tamoxifen-treated patients is consistent with the twofold relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.

Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.

BACKGROUND: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992. METHODS: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. RESULTS: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. CONCLUSIONS: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.

Isolation of lung carcinoma-associated antibodies from immune complexes and production of heterologous antisera.

Immune complexes isolated from pleural effusions of lung carcinomas were dissociated by ion exchange chromatography in the presence of 8 M urea. The antibodies thus obtained from 2 lung adenocarcinomas and 2 squamous cell carcinomas were assayed by indirect immunofluorescence against a variety of target cells in fresh suspensions, tissue cultures, and paraffin-embedded sections. Strong cytoplasmic fluorescence was obtained with greater than 90% of the cell populations of all major histological types of lung carcinomas, and negative fluorescence was obtained with the cells of normal lung tissues and most of the nonpulmonary carcinomas. Antigen fractions prepared from the same lung carcinoma-associated immune complexes were used to immunize rabbits for the production of antisera directed against human lung carcinoma. The rabbit antibody preparations after proper absorptions were assayed in indirect immunofluorescence showing patterns of reactivity with normal and tumor cells of various derivations similar to those obtained with the human antibodies. Complete blocking of immunofluorescence staining with both allogeneic and xenogeneic antibody preparations was achieved by prior absorption with lung tumor tissue extracts or with various lung tumor antigen preparations. The present study demonstrates the isolation from lung tumor effusion immune complexes of antibodies with high affinity for lung carcinoma cells and of antigens that can be used to produce tumor-directed heterologous antibodies. The immunofluorescence staining of lung carcinoma-associated antigens in situ on paraffin-embedded sections provides new, topographical information.

Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study.

PURPOSE: This is the initial report from the health-related quality of life (HRQL) component of the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. This report provides an overview of HRQL findings, comparing tamoxifen and placebo groups, and advice to clinicians counseling women about the use of tamoxifen in a prevention setting. PATIENTS AND METHODS: This report covers the baseline and the first 36 months of follow-up data on 11,064 women recruited over the first 24 months of the study. Findings are presented from the Center for Epidemiological Studies-Depression Scale (CES-D), the Medical Outcomes Study 36-Item Short Form Health Status Survey (MOS SF-36) and sexual functioning scale, and a symptom checklist. RESULTS: No differences were found between placebo and tamoxifen groups for the proportion of participants scoring above a clinically significant level on the CES-D. No differences were found between groups for the MOS SF-36 summary physical and mental scores. The mean number of symptoms reported was consistently higher in the tamoxifen group and was associated with vasomotor and gynecologic symptoms. Significant increases were found in the proportion of women on tamoxifen reporting problems of sexual functioning at a definite or serious level, although overall rates of sexual activity remained similar. CONCLUSION: Women need to be informed of the increased frequency of vasomotor and gynecologic symptoms and problems of sexual functioning associated with tamoxifen use. Weight gain and depression, two clinical problems anecdotally associated with tamoxifen treatment, were not increased in frequency in this trial in healthy women, which is good news that also needs to be communicated.

Impact of empiric antibiotics and chest radiograph on delays in the diagnosis of tuberculosis.

SETTING: Maryland Department of Health and Mental Hygiene, Division of Tuberculosis (TB) Control. OBJECTIVES: To assess the implications of antibiotic treatment of presumed community-acquired pneumonia (CAP) on delays in the diagnosis of TB, and to assess the frequency with which chest radiographs (CXRs) were utilized before a diagnosis of pneumonia or pulmonary TB was made. DESIGN: A nested case-control study within a prospective study conducted to assess factors associated with delays in the diagnosis of TB. RESULTS: Cases (n = 85; 54%) were patients who received antibiotics for non-TB diagnoses/indications prior to TB diagnosis, and controls (n = 73; 46%) were patients who had initially received TB therapy. Median health care delay for cases was 39 days vs. 15 days (P < 0.01) for controls. Median antibiotic delay was similar among all antibiotic classes. Of 54 patients who did not have a CXR at their first health care visit, 41 (79%) received empiric antibiotics, compared to 44/105 (42%) who had a CXR (P < 0.01). Only 31/54 (57%) patients initially diagnosed with CAP had a CXR at the time of diagnosis. CONCLUSION: More widespread use of CXR when diagnosing CAP should reduce delays in diagnosing TB, and the unnecessary use of antibiotics.

Patient and health care system delays in pulmonary tuberculosis diagnosis in a low-incidence state.

SETTING: Tuberculosis (TB) patients reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. OBJECTIVE: To determine the extent of delayed diagnosis of TB and to assess patient and provider factors associated with delays. DESIGN: A prospective cohort study. RESULTS: Median patient, health care and total delays were 32, 26 and 89 days, respectively, for 158 patients. Non-white (relative hazard [RH] 0.62; 95% CI 0.39-0.98) and less educated (RH 0.43; 95% CI 0.26-0.72) patients had longer patient delays. English-speaking patients (RH 0.40; 95% CI 0.24-0.68) had increased health care delays, as did patients who received a diagnosis of a respiratory illness and non-TB antibiotics (RH 0.69; 95% CI 0.49-0.96) prior to a TB diagnosis. Patients first presenting to a private physician (51 days) rather than a hospital emergency room (18 days; RH 1.87; 95% CI 1.05-3.33) or public health clinic (10 days; RH 1.79; 95% CI 1.21-2.63) had longer health care delays. When a TB diagnostic tool (chest radiograph or AFB culture) was utilized, a more rapid diagnosis of TB was made. CONCLUSION: Education of the patient population about TB symptoms might reduce delays. Increased physician awareness of the current epidemiology of TB and better use of available diagnostic tools will reduce delays and may reduce TB transmission.

Presence and prognostic significance of antilymphocyte antibodies in symptomatic and asymptomatic human immunodeficiency virus infection.

The presence of antilymphocyte antibody (ALA) in patients with the acquired immunodeficiency syndrome (AIDS), identified in a previous study, was confirmed by testing a population of 200 patients with AIDS. Of these, 88% had significant levels of ALA vs only 8% of a control group of patients with non-AIDS-related diseases. In a prospective study, the levels of ALA were determined in 61 patients with AIDS-related complex who were followed up for 18 to 30 months. During this interval, 31 (67%) of 46 patients with significant elevation of ALA levels developed AIDS, while none of 15 patients without elevation of ALA levels progressed to AIDS. In a group of 85 apparently healthy homosexual men, also followed up for 18 to 30 months, a significant number of those with high levels of ALA developed clinically apparent disease, while those with low levels did not. These results show that the amount of ALA correlates with the present clinical status as well as the future risk of developing immune deficiency.

Transmission of Mycobacterium tuberculosis through casual contact with an infectious case.

BACKGROUND: An ongoing restriction fragment length polymorphism study of Mycobacterium tuberculosis isolates from tuberculosis cases showed an identical 12-band IS6110 pattern unique to 3 unrelated patients (Patients A-C) diagnosed as having tuberculosis within a 9-month period. METHODS: In an attempt to identify epidemiologic links between the 3 patients, we performed site visits to the retail business work site of patient A and conducted detailed interviews with all 3 patients and their contacts. RESULTS: Patient B had visited patient A's work site 3 times during patient A's infectious period, spending no more than 15 minutes each time. Patient C visited patient A's work site on 6 to 10 occasions during this period for no more than 45 minutes at any one time. There were no other epidemiologic links between these 3 cases other than the contact at the store. Contact investigation identified 4 tuberculin skin test conversions among 8 (50%) of patient A's coworkers, 6 positive tests among 15 household contacts (40%), and 8 positive tests among 16 identified customers who were casual contacts (50%). Patient B and patient C were most likely infected by patient A during one of their brief visits to patient A's work site. CONCLUSIONS: These data demonstrate that some tuberculosis is spread through casual contact not normally pursued in traditional contact investigations and that, in certain situations, M tuberculosis can be transmitted despite minimal duration of exposure. In addition, this outbreak emphasizes the importance of DNA fingerprinting data for identifying unusual transmission in unexpected settings.

HIV counseling and testing in tuberculosis contact investigations in the United States and Canada.

BACKGROUND: Determining the human immunodeficiency virus (HIV) status of tuberculosis (TB) patients and contacts is important. Despite existing guidelines, not all patients are tested, and testing of contacts is rarely performed. METHODS: In a study conducted at nine US/Canadian sites, we introduced formal procedures for offering HIV testing to TB patients and contacts. Data were collected via interviews and medical record review. Characteristics associated with offering and accepting HIV testing were examined. RESULTS: Of 651 TB patients, 601 (92%) were offered testing, 511 (85%) accepted, and 51 (10%) were HIV-infected. Of 4152 contacts, 3099 (75%) were offered testing, 1202 (39%) accepted, and 24 (2%) were HIV-infected. Contacts aged 15-64 years, non-Whites, foreign-born persons, smokers, those with positive TB screening, and household contacts were more likely to be offered testing, whereas contacts exposed to HIV-negative patients were less likely to be offered testing. Contacts aged 15-64 years, smokers, drug/alcohol users, diabetics, and those with positive TB screening were more likely to accept testing. Foreign-born persons, Blacks, Hispanics, and contacts exposed to HIV-positive patients were less likely to accept testing. CONCLUSIONS: High rates of HIV were detected among patients and contacts. Despite structured procedures to offer HIV testing, some patients and most contacts did not accept testing. Strategies are needed to improve testing acceptance rates.

Cardiovascular parameters in a mixed-sex swine study of severe decompression sickness treated with the emulsified perfluorocarbon Oxycyte.

Intravenous perfluorocarbons (PFC) have reduced the effects of decompression sickness (DCS) and improved mortality rates in animal models. However, concerns for the physiological effects of DCS combined with PFC therapy have not been examined in a balanced mixed-sex population. Thirty-two (16 male, 16 female) instrumented and sedated juvenile Yorkshire swine were exposed to 200 feet of seawater (fsw) for 31 min of hyperbaric air. Pulmonary artery pressure (PAP), cardiac output (CO), and systemic arterial pressure (SAP) were monitored before (control) and after exposure. Animals were randomized to treatment with Oxycyte (5 ml/kg; Oxygen Biotherapeutics, Inc., Morrisville, NC) vs. saline (control) with 100% oxygen administered upon DCS onset; animals were observed for 90 min. Parameters recorded and analyzed included PAP, CO, and SAP. In all animals PAP began to rise prior to cutis marmorata (CM) onset, the first sign of clinical DCS, generally peaking after CM onset. Female swine, compared with castrated males, had a more rapid onset of CM (7.30 vs. 11.46 min postsurfacing) and earlier onset to maximal PAP (6.41 vs. 9.69 min post-CM onset). Oxycyte therapy was associated with a sustained PAP elevation above controls in both sexes (33.41 vs. 25.78 mmHg). Significant pattern differences in PAP, CO, and SAP were noted between sexes and between therapeutic groups. There were no statistically significant differences in survival or paralysis between the PFC and control groups during the 48-h observation period. In conclusion, Oxycyte therapy for DCS is associated with a prolonged PAP increase in swine. These species and sex differences warrant further exploration.

Investigation of Laboratory cross-contamination of Mycobacterium tuberculosis cultures.

Many clinicians and laboratory personnel are unaware that a culture positive for Mycobacterium tuberculosis may represent contamination. Laboratory cross-contamination with the M. tuberculosis laboratory control strain (H37Ra) occurs infrequently and therefore demands heightened awareness and recognition. We report 3 occurrences of laboratory cross-contamination from the same laboratory. These occurrences illustrate the importance of interpreting laboratory results in conjunction with the patient's clinical presentation. Failure to recognize laboratory cross-contamination with M. tuberculosis leads to both erroneous administration of unnecessary medications and expenditure of resources required to conduct contact investigations.

Anti-lymphocyte antibodies in patients with the acquired immune deficiency syndrome.

Human lymphotropic retroviruses lymphadenopathy-associated virus/human T lymphoma virus III have been recently implicated in the pathogenesis of the acquired immune deficiency syndrome (AIDS). The mechanisms leading to the complex immune deregulations of this disease, however, are still largely unknown. To investigate the possible presence of anti-lymphocyte antibodies, lymphocytes from a normal donor were incubated with serum samples from patients with AIDS. Substantial increases of up to 75 percent in the number of surface immunoglobulin-positive lymphocytes resulted from incubation with serum of patients with AIDS and AIDS-related complex but not with serum of patients with non-AIDS-related diseases or of normal control subjects. Monoclonal antibodies to OKT11, OKT4, and OKT8 in conjunction with a double-labeling technique were then used to identify the type of surface immunoglobulin-positive lymphocytes. These experiments showed that binding of immunoglobulins to lymphocytes did not occur at random but was directed against OKT4- or OKT11-positive cells whereas OKT8-positive cells showed no detectable reactivity. The results of these studies indicate that patients with AIDS and AIDS-related complex have circulating antibodies capable of reacting selectively with a population of T cells that is predominantly composed of helper cells and does not include suppressor cells. The augmentation of surface immunoglobulin-positive lymphocytes in the patients studied consistently paralleled the marked decreases of the helper/suppressor cell ratios and the presence of circulating anti-human T lymphoma virus III antibodies. Binding of antibodies to the surface of helper T cells may be a determining event in the pathogenesis of this disease.

Acquired immunodeficiency syndrome-associated lymphomas: clinical, pathologic, immunologic, and viral characteristics of 111 cases.

The incidence of lymphomas in individuals infected with the human immunodeficiency virus has increased progressively since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic. The present series includes 111 patients, all diagnosed and studied at one hospital in New York City. There were 108 men and three women; the average age was 39 years and male homosexuality was the predominant risk factor. The materials examined originated from 138 surgical specimens and 24 autopsies. There were 11 cases of Hodgkin's lymphoma and 100 cases of non-Hodgkin's lymphomas (NHL), a proportion strongly skewed in favor of the latter. Hodgkin's lymphoma in AIDS patients was characterized by advanced clinical stage, high histologic grade, and frequent bone marrow involvement. Non-Hodgkin's lymphoma in AIDS patients, in contrast to the general population, originated predominantly in extranodal locations (61 cases) versus locations in which the lymph nodes were the site of the primary tumors (39 cases). In the digestive tract, the unusual oral and anal primary locations were often noted and were possibly related to specific risk factors. There were 15 cases of NHL of the central nervous system, an incidence 14 times greater than that recorded in the general population. The majority of NHLs were of high histologic grade, Burkitt's and large cell immunoblastic, representing most of the cerebral and gastrointestinal tumors. All NHLs were of B-cell immunophenotype. Lymphadenopathies with the histologic features of human immunodeficiency virus infection, particularly of the late stage (type C), often preceded NHL. Probing for Epstein-Barr virus genome was more frequently positive in Hodgkin's lymphoma than in NHL. Immunologic evaluations showed severely depressed T cell counts and CD4 to CD8 cell ratios as well as markedly increased levels of antilymphocyte antibodies. Reflecting the background of profound immune deficiency, the AIDS-associated lymphomas were characterized by high aggressiveness, early tendency to generalization, frequent post-treatment relapse, and short periods of survival.

Collaborative education regarding prevention of human immunodeficiency virus transmission in healthcare settings--Ghana.

OBJECTIVE: To evaluate the effectiveness of a collaborative and participatory approach to professional training to reduce the risk of human immunodeficiency virus (HIV) transmission. SETTING: Healthcare settings in Ghana. METHODS: Two 5-day workshops were conducted for high-level nurse educators and leaders who could contribute to national policy development. A combination of didactics, skill development sessions, field experiences, and development of draft national guidelines and curriculum were used. Outcomes evaluated were pre-to-post training changes in HIV knowledge and attitudes and changes in practice within selected healthcare settings. One-month follow-up visits (times not specified to participants) were used to evaluate outcomes. RESULTS: At post-test, significantly fewer participants thought HIV was transmitted by saliva, sweat, or tears (chi square, p less than .0001), and significantly fewer reported hesitation to care for an HIV-infected patient because of lack of understanding about mode of transmission or because of lack of supplies, such as gloves (chi square, p less than .01). In field observations, there was an overall 42% improvement in specific infection control practices. CONCLUSIONS: A collaborative and participatory approach to training can result in significant changes in infection control practices, even in settings with limited resources.

Intravascular catheter colonization and related bloodstream infection in critically ill neonates.

Intravascular catheter tip colonization was prospectively evaluated in critically ill neonates to determine its relationship to the type of device used, duration of catheterization, insertion site and nosocomial bloodstream infection. Sixty-one percent (376 of 621) of all intravascular catheter tips were retrieved from 91 infants. Thirteen percent (41 of 310) of peripheral intravenous, 14% (6 of 42) of umbilical, 21% (3 of 11) of central venous, 36% (4 of 11) of peripheral arterial and 100% (2 of 2) of femoral catheters were colonized. Duration of catheterization was significantly longer for colonized lines (p less than .001). Eight of 26 (30.8%) peripheral intravenous catheters remaining in place for more than three days were colonized, compared with 33 of 284 (11.6%) at three days or less (p = 0.012). Coagulase-negative staphylococcus was the organism most frequently isolated from catheter tips and bloodstream infections. Catheter colonization rates in this population were higher than those found in adults. Heavily manipulated devices and those in place for longer periods of time were the most frequently colonized.

Pseudo-outbreak of tuberculosis in an acute-care general hospital: epidemiology and clinical implications.

A 10-fold increase in patients with Mycobacterium tuberculosis-positive specimens in one hospital laboratory prompted an investigation. Clinical and epidemiological data, along with M tuberculosis DNA fingerprinting results, indicated that laboratory contamination led to nine false-positive M tuberculosis cultures. Pseudo-infection should be considered in patients with unusual tuberculosis presentations, negative acid-fast bacilli smears, and only one positive culture with a low colony count.

Persistent lymphadenopathies in people at high risk for HIV infection. Clinicopathologic correlations and long-term follow-up in 79 cases.

Clinicopathologic correlations were explored in 79 patients at high risk for human immunodeficiency virus (HIV) infection who had lymph node biopsy for persistent lymphadenopathies and were followed for intervals of up to 7.2 years. Three histologic patterns, follicular hyperplasia with cytolysis (A), follicular involution with hypervascularity (C), and a combination of the previous two (B), were recognized. Ninety lymph node biopsies (79 primary and 11 sequential) were classified into the three histologic patterns and the results correlated with the immunologic data and clinical course. Of 31 patients who showed a pattern A at the initial biopsy, the condition of 58% remained stationary and 42% progressed to acquired immune deficiency syndrome (AIDS); of 31 patients who had initial B pattern, the condition of 36% remained stationary and 64% progressed to AIDS; and of 17 patients who initially had histologic pattern C, the condition of 6% remained stationary and 94% progressed to AIDS. Forty-one patients died during this follow-up, representing 32% of those who had a pattern A, 52% of those who had a pattern B, and 88% of those who had a pattern C at the initial lymph node biopsy. Medial survival times were 54.4 months for pattern A, 35.6 months for pattern B, and 8.4 months for pattern C. Sequential biopsies showed persistence of the same pattern or changes generally in the direction of pattern A to pattern C over variable amounts of time. Lymphocyte evaluation expressed by total counts of T4 cells, T8 cells, T4/T8 cell ratios, and anti-lymphocyte antibody levels expressed by increases in counts of surface immunoglobulin-positive lymphocytes showed positive correlations with lymph node histologic patterns. All three parameters proved to be useful prognostic indicators for the course of the HIV infection. The pathogenetic significance of lymph node histologic patterns, although not clearly understood, suggests the relation of follicular hyperplasia (pattern A) to acute viral lymphadenitis and of follicular involution with hypervascularity (pattern C) to cellular immune deficiency.

Detection of HIV-related protein in testes and prostates of patients with AIDS.

The testes and prostates of 14 patients with acquired immune deficiency syndrome (AIDS) for whom autopsies were performed were examined for the presence of human immunodeficiency virus (HIV) and the pathologic alterations seen in AIDS. Histologically, the testes contained peritubular fibrosis and variable spermatogenic arrest, which were inconsistent with the young age of these patients. There were also numerous foci of germ cell degeneration and occasional germ cell loss. The Leydig cells were atrophic and decreased in number. The prostates contained increased numbers of concretions. Sections of testis and prostate were stained with an anti-HIV P17 monoclonal antibody with the use of the avidin-biotin technique. Small scattered foci of positive staining were identified in 8 of 14 testes (57%). They were located over one or several degenerating germ cells and the surrounding Sertoli cells. In addition, in 9 of 14 prostates (64%) there were a few minute foci of positive staining in several adjacent glandular epithelial cells. In one case the testis was positive and the prostate was negative, whereas in two cases the testes were negative and the prostate positive. In contrast, 22 testes and 22 prostates of control non-AIDS patients, read double-blind, were negative. The positive controls were HIV-infected tissue culture HUT 78 lymphoma cells in which there were many scattered positive cells. The results indicate the presence of focal HIV-associated protein in the testes and prostates of patients with AIDS, particularly within the foci of germ cell degeneration. The present observations are in accordance with previous research demonstrating the presence of HIV in the seminal fluid of patients with AIDS and appears to indicate the presence of an infection of the male genital tract by the HIV virus.

Evaluation of an extensive tuberculosis contact investigation in an urban community and jail.

SETTING: Urban community and jail. OBJECTIVES/DESIGN: Evaluate outcome and process of an extensive tuberculosis contact investigation, including completion of treatment of latent TB infection (TLTBI). RESULTS: Between April 2000 and September 2001, 18 epidemiologically-linked tuberculosis cases were identified; 15 were culture-confirmed, all with a matching 14-band DNA fingerprint pattern. The source case had cavitary pulmonary disease and had been incarcerated 4 months prior to diagnosis. Sixty-six of 67 (99%) community contacts and 221/344 (64%) jail contacts were evaluated. The presumed new infection rate was 56% for community contacts (11 cases, 25 tuberculin skin test [TST] positive) and 20% for jail contacts (6 cases, 32 TST converters). Screening results for 113 (33%) jail contacts were obtained in the jail TST registry upon rearrest. All identified cases completed treatment. Of 22 community contacts initiating TLTBI, 11 completed (44% of infected, 50% of initiators). Of 32 infected jail contacts, 12 initiated TLTBI (all who remained incarcerated), and 10 completed (31% of infected, 83% of initiators). None of 20 additional in-fected jail contacts, all of whose TST conversions were identified with re-arrest data, were subsequently located. Two additional related cases have been identified as of October 2003. CONCLUSIONS: Close health department/corrections collaboration facilitated this extensive contact investigation, which identified high Mycobacterium tuberculosis transmission rates and controlled the outbreak. Numerous contacts were identified and screened, but rates of treatment completion for infected contacts were low. Novel strategies are needed to maximize the number of infected contacts who are not only identified and evaluated, but completely treated.