Are HTLV-II-seropositive injection drug users at increased risk of bacterial pneumonia, abscess, and lymphadenopathy?

Disease associations of HTLV-II are poorly defined, despite a high seroprevalence among injection drug users (IDU). One hundred twenty-four HTLV-II-seropositive emergency room and clinic patients were matched by age, sex, and clinic to 120 HTLV-I/II-seronegative patients. Medical records were reviewed blinded to HTLV-II status, and International Classification of Disease 9th Clinical Modification (ICD-9CM)-coded diagnoses were compared between seropositive patients and controls. After adjustment for relevant confounding variables such as human immunodeficiency virus infection, HTLV-II-seropositive IDU had an increased risk of bacterial pneumonia (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.58, 7.56), abscess (OR, 8.30; 95% CI, 4.02, 17.11), and lymphadenopathy (OR, 3.91; 95% CI, 1.24, 12.32) compared with HTLV-II-negative non-IDU patients. In contrast, HTLV-II-negative IDU were at only marginally increased risk of the same conditions, with OR of 1.76 (95% CI, 0.42, 7.40), 3.00 (95% CI, 0.94, 9.59), and 1.31 (95% CI, 0.15, 11.66), respectively. These results indicate that HTLV-II seropositivity may define a subgroup of IDU who are at particularly high risk of bacterial pneumonia, skin and soft tissue abscess, and lymphadenopathy. Whether HTLV-II has an etiologic role in predisposing IDU to bacterial infections and lymphadenopathy will require further investigation.

Acetaminophen and salicylate serum levels in patients with suicidal ingestion or altered mental status.

Is universal screening of acetaminophen (APAP) and salicylate (SAL) necessary in patients with a suicidal ingestion or an altered mental status and suspected ingestion? This descriptive, retrospective chart review in an emergency department in a large urban county hospital examined all patients who presented with a history of suicidal ingestion or an altered mental status with a strong suspicion of ingestion from January 1992 through October 1993. APAP and SAL serum levels were measured in 1,820 patients, and charts of patients with APAP serum levels of > 1 microgram/mL or SAL serum levels of > 1 mg/dL were reviewed. The patient's history of ingesting APAP or SAL was recorded, as well as the clinician's interpretation of that level. Sixteen charts were not available. APAP levels of > 1 microgram/mL were found in 175 (9.6%) patients, 120 (6.5%) of whom were APAP history-positive and 55 (3%) APAP history-negative. None of the APAP history-negative group required therapy with N-acetylcysteine. Eight (0.3%) of the APAP history-negative group had potentially toxic levels of > 50 micrograms/mL. SAL levels of > 1 mg/dL were found in 155 (8.5%) patients, 44 (2.5%) of whom were SAL history-positive and 111 (6%) SAL history-negative. Three patients were SAL history-negative but had a significant chronic SAL intoxication. All these patients presented with an altered mental status and had an anion gap of > 20 mEq/L. Universal screening found that 0.3% of suicidal ingestions had a potentially toxic APAP intoxication not suggested by history. This incidence of infrequent but potentially life: threatening overdose should prompt clinicians to screen all of their patients with a suspected ingestion. Salicylate screening found that 0.16% of suicidal ingestions had a toxic SAL intoxication not suggested by history, although such intoxication should be suggested by an elevated anion gap and an altered mental status. Since this less severe intoxication is less frequent and usually suggested by commonly obtained laboratory data, universal screening is not indicated, but a more selective approach to screening could be taken.

Discrepancies in osmolal gaps and calculated alcohol concentrations.

OBJECTIVES: To estimate unexplained osmolal gaps (UEOG) during ethanol ingestions after accounting for measured ethanol concentrations and to explore the causes of observed discrepancies. DESIGN AND SPECIMENS: A random convenience sample of serum specimens with a request to perform osmometry for the detection of alcohols was studied. MAIN OUTCOME MEASURES: Serum concentrations of sodium, glucose, urea nitrogen, ethanol, osmolality, and ethanol were measured by two analytic methods to determine calculated osmolalities and osmolal gaps using two commonly used formulas. RESULTS: In 79 serum specimens submitted for osmometry, mean ethanol concentrations were 199 +/- 154 (SD) mg/dL; 15 specimens had no detectable ethanol. After regression of the calculated ethanol concentrations and the measured ethanol concentrations, the Dorwart and Chalmers formula showed a large constant bias of 45.217 +/- 6.414 (SE) mOsm/kg in predicting measured ethanol concentrations. The Smithline and Gardner formula was similarly as precise (r = .9786), but had a much smaller bias of -3.929 +/- 6.623 (SE) mOsm/kg. Actual mean differences between measured and calculated osmolalities (including ethanol osmols) gave an estimate of UEOG seen during ethanol ingestions. Using the less biased formula, the mean UEOG was 1.4 +/- 8.5 mOsm/kg, giving a 95% upper limit of the reference range of 18 mOsm/kg in this population with ethanol ingestions. Three significant outliers were identified and their UEOG could be explained by the presence of mannitol, isopropanol, or possibly a change in the assumed value for fractional water, normally a constant in these formulas for calculated osmolality. Other specific causes of osmolal gap and UEOG are discussed. CONCLUSION: The potential range of osmolal gaps seen during ethanol ingestions after accounting for ethanol is demonstrated to be greater than in previous studies, which have included a lower proportion of ethanol-intoxicated subjects in their study sample.

Human T-lymphotropic virus type II seroprevalence among emergency department and clinic patients.

To determine the seroprevalence of human T-lymphotropic virus types I and II (HTLV-I and HTLV-II) among emergency department and clinic patients at a San Francisco, California, hospital, consecutive patients from 4 outpatient settings-emergency department, medical clinic, antenatal clinic, and neighborhood health centers-were tested for antibody to 1 of the viruses using an enzyme-linked immunosorbent assay and Western blot test. Of 4,019 patients, 169 (4.2%) had antibody to HTLV-I or -II; the seroprevalence of HTLV-II (3.5%) was greater than that of HTLV-I (0.7%). Seroprevalence for HTLV-II was highest in the emergency department (6.9%) and neighborhood clinics (3.9%) and in those aged 30 to 59 years (5.9%). Crude HTLV-II prevalence was higher in men (5.2%) than in women (2.2%), but sex was not an independent risk factor after age and location were controlled for. This study showed a higher seroprevalence of HTLV-I and HTLV-II among outpatients than did previous studies, probably because of a high proportion of injection-drug users. In view of the recent description of HTLV-II-associated myelopathy, studies of neurologic disease in this population may be warranted. HTLV-II should be included in the list of occupationally transmitted infections for hospitals with many injection-drug-using patients.

Seroprevalence of human T-lymphotropic virus, hepatitis C virus, and human immunodeficiency virus in Asian American potential bone marrow donors.

BACKGROUND: Asian Americans are generally underrepresented both as volunteer blood and bone marrow donors. STUDY DESIGN AND METHODS: To investigate the risk of transfusion transmission of viruses that is associated with increasing participation by Asian American donors, antibodies to human T-lymphotropic virus (HTLV), hepatitis C, and human immunodeficiency virus in Asian American volunteers recruited as potential bone marrow donors were measured. A total of 1354 Asian Americans were enrolled in the study, of whom 54 percent were Chinese, 26 percent Japanese, 9 percent Filipino, 4 percent Korean, 3 percent Indian, and 5 percent of other Asian or mixed Asian and other ethnicity. The majority of the study population was aged 20 through 49 and of high socioeconomic status, as indicated by education and income. Viral antibodies were measured with both screening enzyme-linked immunosorbent assays and supplemental testing, and polymerase chain reaction was used to resolve discrepant HTLV results. RESULTS: Confirmed seroprevalence rates for HTLV were 0.15 percent with one manufacturer's Western blot and 0.3 percent with the other; however, no sample was positive for HTLV types I or II in polymerase chain reaction. Confirmed seroprevalence to hepatitis C virus was 0.5 percent. No subject was seropositive for human immunodeficiency virus. CONCLUSION: On the basis of the moderate size and high education level of this study population, it is concluded that Asian American volunteer bone marrow donors do not pose a greater risk for transmission of HTLV type I or II, human immunodeficiency virus, or hepatitis C virus than does the average American blood donor.

Human T-lymphotropic virus type I seroprevalence among Japanese Americans.

The epidemiology of human T-lymphotropic virus type I (HTLV-I) infection is not well defined in Japanese Americans. This impairs using approaches that could reduce viral transmission and monitor carriers for the disease. Using enzyme-linked immunosorbent assay and p21e recombinant Western blot testing, HTLV-I antibody was measured in unlinked samples from Japanese-American patients at 4 physicians' offices in San Francisco, California. Of 442 patients, 4 (0.9%; 95% confidence interval 0.25%, 2.3%) were confirmed seropositive, all with an HTLV-I rather than an HTLV-II pattern on Western blot. Seroprevalence was highest among the issei or immigrant generation (3/230 or 1.3%) compared with the second-generation nisei (1/191 or 0.5%) or third-generation sansei (0 of 17). Prevalence did not differ by age or sex, although the number of positive subjects in each subgroup was small. Of 88 patients with familial origins in endemic areas of southern Japan, none were seropositive. In this sample of Japanese Americans, HTLV-I seroprevalence was lower than in residents of endemic southern Japan but higher than among American blood donors. The prevalence was most similar to that in nonendemic areas of Japan. The public health implications of HTLV-I infection among Japanese Americans are discussed.

Determination of human T lymphotropic virus type by polymerase chain reaction and correlation with risk factors in northern California blood donors.

To determine the relative prevalence of human T lymphotropic virus (HTLV) types I and II, type-specific polymerase chain reaction (PCR) was done on seropositive northern California blood donors. From October 1988 through March 1990, 67 (0.055%) of 122,517 blood donors had confirmed HTLV antibody. Seropositive donors were more likely to be middle-aged, female, and nonwhite than the overall donor base. PCR of samples from 30 HTLV-seropositive donors yielded 19 (63%) with HTLV-II and 9 (30%) with HTLV-I; 2 (7%) were repeatedly negative by PCR. HTLV-I-infected subjects had ancestry (n = 3), sexual contact (n = 3), or paternal military service in (n = 1) Japan or the Caribbean. HTLV-II carriers reported past intravenous drug abuse (n = 3) or sex with a drug user (n = 11). Two carriers of each type reported previous blood transfusions, and 1 HTLV-II carrier was a dentist with no other risk factors for retroviral infection.

Resolution of infection status of human immunodeficiency virus (HIV)-seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence area.

To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation.

Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells.

BACKGROUND: Reports of transmission of the human immunodeficiency virus type 1 (HIV-1) from transfusions of screened blood and reports of silent, antibody-negative HIV-1 infections in persons at high risk continue to foster concern about the safety of the blood supply. Previous estimates of the risk of HIV-1 range from 1 in 38,000 to 1 in 300,000 per unit of blood but are based on either epidemiologic models or the demonstration of seroconversion in recipients. METHODS: We isolated peripheral-blood mononuclear cells from blood that was fully screened and found to be seronegative, combined them into pools of cells from 50 donors, and tested them for HIV-1 by viral culture and the polymerase chain reaction, using protocols specifically adapted for this analysis. RESULTS: The 1530 pools of mononuclear cells were prepared from 76,500 blood donations made in San Francisco between November 1987 and December 1989. Of these pools, 1436 (representing 71,800 donations) were cultured successfully; 873 (43,650 donations) were evaluated by the polymerase chain reaction. Only one pool was confirmed as HIV-1--infected by both methods. After adjustment for sample-based estimates of the sensitivity of the detection systems using culture and the polymerase chain reaction, the probability that a screened donor will be positive for HIV-1 was estimated as 1 in 61,171 (95 percent upper confidence bound, 1 in 10,695). CONCLUSIONS: Silent HIV-1 infections are exceedingly rare among screened blood donors, so the current risk of HIV-1 transmission from blood transfusions, even in high-prevalence metropolitan areas, is extremely low.

Comparative analysis of antiepileptic drugs by gas chromatography using capillary or packed columns and by fluorescence polarization immunoassay.

The gas chromatographic (GC) quantification of underivatized antiepileptic drugs such as carbamazepine, phenytoin, phenobarbital and primidone in fused-silica capillary columns was compared with that in packed columns. Excellent correlation was demonstrated between the two column methods by slopes of 0.99 to 1.05, by Y-intercepts of -0.47 to 0.28 and by r values of 0.996 and 0.997. In addition, some of the specimens from GC analysis by both column methods were compared with data obtained for these drugs as analyzed with the Abbott TDx system. Data obtained by both GC column methods showed excellent correlation.

Persistent immune complexes and abnormal CD4/CD8 ratios in HIV infection.

We assessed the immunopathologic role of circulating immune complexes in human immunodeficiency virus infection by evaluating the data base and the serum bank of the San Francisco Men's Health Study, a longitudinal clinical and epidemiological investigation conducted since 1983. A group of 4,276 sera from 1,023 (including 811 homosexual/bisexual) men were tested for circulating immune complexes. We used a modification of the commercially available enzyme immunoassay test, based on monoclonal anti-C1q antibodies coupled to the solid phase, for capturing circulating immune complexes from the test serum, followed by detection of circulating immune complexes with either anti-IgG or with anti-IgM probes. Although persistent IgM and IgG circulating immune complexes were most frequently encountered in human immunodeficiency virus-seropositive homosexual/bisexual men, they were not an indicator of disease progression as assessed by abnormalities in the absolute numbers or ratios of CD4- and CD8-positive T cells, or clinical signs and symptoms of AIDS/ARC.

The clinical significance of human immunodeficiency virus type 1-associated paraproteins.

We observed and characterized paraproteins present in the serum of seven human immunodeficiency virus type 1 (HIV-1)-infected individuals. Immunoglobulin (Ig) subclass typing performed on these paraproteins identified five as IgG1 kappa, one as an IgG3 lambda, and one as an IgA lambda. The IgG1 kappa paraproteins, purified by high-pressure liquid chromatography, contained the majority of anti-HIV-1 antibody reactivity present in the five serum specimens (ranging from 1:5,000 to 1:500,000) as demonstrated by immunoblot. All five IgG1 paraproteins had at least two light chain species as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the antibodies were reactive with multiple HIV-1 viral antigens. In contrast, the electrophoretically purified IgG3 lambda and IgA lambda paraproteins did not react with HIV-1 antigens and only one light chain species was detected by SDS-PAGE. The subsequent clinical evaluation of these patients following the initial observation of paraproteinemias failed to correlate the presence of paraproteins with the development of lymphoma over a 2 to 3 year period. These data support the hypothesis that IgG1 paraproteins present in the sera of HIV-1 infected individuals reflect a normal albeit exuberant polyclonal immune response to HIV-1 viral antigens. In contrast, the clinical significance of an IgG3 lambda or an IgA lambda paraprotein is unclear at present.

Value of rapid screening for acetaminophen in all patients with intentional drug overdose.

We performed a prospective study to determine the incidence of missed, potentially toxic acetaminophen poisoning in all patients with any type of intentional drug ingestion presenting to two large, county hospital emergency departments. Of 486 patients with drug ingestion seen during a five-month period, 114 (23.5%) were suspected of having ingested acetaminophen. Of these, 71 (62.3%) had insignificant acetaminophen levels (false-positive history). Of the 365 patients who were not suspected of having acetaminophen ingestion, seven patients (1.9%) were found to have elevated levels on rapid screening (false-negative history). Of these, only one patient had a potentially hepatotoxic level. We conclude that the incidence of missed, potentially serious acetaminophen overdose is very low in our study population.

Extreme hypermagnesemia caused by an overdose of magnesium-containing cathartics.

We describe a patient who survived a peak serum magnesium level of 9.5 mmol/L (23.0 mg/dL) after an oral cathartic overdose. The patient presented in coma but regained full consciousness over the next six hours with supportive therapy. His serum magnesium had returned to near-normal levels by the following morning at the time of his hospital discharge. This case represents an unprecedented extent of ingestion-related hypermagnesemia in a surviving patient, given that serum levels of more than 8 mmol/L are frequently associated with death from cardiac arrest.

High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex.

We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. Serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-HIV antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24-Sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.

Immunofixation compared with immunoelectrophoresis for the routine characterization of paraprotein disorders.

The authors prospectively compared immunofixation electrophoresis (IFE) with immunoelectrophoresis (IEP) for the evaluation of paraproteins in 32 patient specimens. They used a simple modification of their existing agarose protein electrophoresis system for IFE. Thirteen specimens (40%) required IFE for paraprotein identification, 18 (56%) were definitive by either method, and 1 (3%) did not show a paraprotein by either method. Low titer and/or avidity with anti-lambda antibody from three of seven suppliers prevented or complicated interpretation of IEP patterns with two of four known lambda paraprotein-containing specimens but had no such effect with IFE. In view of these and various additional technical considerations, the authors suggest IFE for the routine characterization of paraproteins in the serum or urine.