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Biomedical subjects

H W Horowitz

Publications and source records attributed to H W Horowitz.

At least 55 records · Page 3Linked to original sources

Comparison of major antigenic proteins of six strains of the human granulocytic ehrlichiosis agent by Western immunoblot analysis.

The etiologic agent of human granulocytic ehrlichiosis (HGE) is an obligate intracellular bacterium. In 1996, blood specimens from 53 patients suspected of having HGE were examined by indirect fluorescent antibody (IFA) testing with the HGE agent no. 13 isolate as the antigen, by nested PCR, and by culture. All patients resided in Westchester County, N.Y. Twelve patient specimens were positive for IFA (titer > or = 1:40). Seven of these were also positive by PCR. Of the seven specimens positive by both IFA testing and PCR, the HGE agent was isolated from four (no. 2, 3, 6, and 11) and continuously cultured in HL-60 cells. These were confirmed as the HGE agent by sequencing of 16S rDNA. Both purified whole-cell organisms and the outer membrane fractions of the new isolates were compared with no. 13 isolate and a tick (USG) isolate by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western immunoblot analysis. No. 11 and 13 isolates had identical SDS-PAGE patterns with respect to 49- and 47-kDa proteins. No. 3 and USG isolates lacked the 47-kDa protein, and no. 6 isolate lacked the 49-kDa protein. Both 49- and 47-kDa bands were absent in no. 2 isolate. Western blot results with seven different sera, including five convalescent-phase sera from these patients, one dog anti-USG isolate, and one horse anti-BDS isolate, showed that all major antigens in six isolates were recognized by all sera. However, the molecular sizes and the numbers of major antigens recognized varied among the six isolates. Overall, HGE agent no. 3, 6, 11, and 13, and USG isolates had similar patterns, with 1 or 2 major antigens with molecular masses of around 49 and 47 kDa. No. 2 isolate was quite distinct in having a major antigen of 43 kDa. This indicates that although these antigenic epitopes are all cross-reactive among strains, the HGE agent has a strain pleomorphism in its major antigenic proteins. The major antigen profiles of the outer membrane protein fractions and of whole organisms of six HGE agent isolates were similar, suggesting that 49- and 47-kDa major antigens are the outer membrane proteins of the HGE agent.

Animals↗

Human granulocytic ehrlichiosis: a case series from a medical center in New York State.

BACKGROUND: Human granulocytic ehrlichiosis (HGE) is a newly described illness with few reports in the literature. OBJECTIVE: To describe the clinical and laboratory feature of HGE. DESIGN: Case series. SETTING: Tertiary care facility in New York State. PATIENTS: 18 adult patients with HGE. MEASUREMENTS: Epidemiologic, clinical, and laboratory features; treatment; and outcome of patients with HGE. RESULTS: Patients presented with such symptoms as fever (94%) and myalgia or arthralgia (78%). Thirteen patients (71%) recalled being bitten by a tick before onset of symptoms. Leukopenia or thrombocytopenia was seen in 82% of patients, and abnormal liver enzyme levels were seen in 81%. Results of polymerase chain reaction were positive in 9 of 12 patients (75%); morulae were seen in 3 of 12 patients (25%); and the agent that causes HGE was cultured from 2 patients. All but one patient (94%) developed antibodies to Ehrlichia equi. Five patients (28%) were briefly hospitalized, and none died. All patients were successfully treated with doxycycline. CONCLUSIONS: The illness associated with HGE in these patients from the northeastern United States was more mild than that originally described in reports of HGE in the midwestern United States.

Adult↗

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗

Brachial plexopathy associated with human granulocytic ehrlichiosis.

Human granulocytic ehrlichiosis is a tick-borne disease of humans. Involvement of the peripheral nervous system is well known with Lyme disease and some rickettsioses but has yet to be described with this disease. We describe a man with bilateral brachial plexopathies associated with an acute febrile illness and clinical, laboratory, and serologic evidence diagnostic of human granulocytic ehrlichiosis. The clinical presentation suggests that the peripheral neuropathy was postinfectious. Human granulocytic ehrlichiosis should be considered in the differential diagnosis in patients with peripheral nervous system involvement, including brachial plexopathy, of individuals who live or recreate in areas known to harbor ticks.

Adult↗

Stepdown single agent antibiotic therapy for the management of the high risk neutropenic adult with hematologic malignancies.

The standard of therapy for the high risk adult neutropenic host being treated with broad spectrum antibiotics for fever has been to continue intravenous antibiotics until neutropenia resolves. We performed a small, limited pilot study to determine if it is safe to switch these patients to oral monotherapy with ciprofloxacin. Ten patients with hematologic malignancies who had < or = 108 granulocytes/mm3 after cytoreductive therapy and were afebrile for at least five days had intravenous antibiotics discontinued and were placed on oral ciprofloxacin. Eight patients were able to be discharged from the hospital and seven were treated without the need for reinstitution of intravenous therapy. Of the three failures, one developed fever with a new bloodstream infection and two developed fever with relapse of leukemia. Patients remained on ciprofloxacin an average of 14.5 days (range 4 to 35 days). Aggregate cost savings for the 10 patients from this approach were estimated to be $11,400 for antibiotics and $88,800 for hospitalization. If corroborated in larger, randomized studies, the use of "stepdown monotherapy" may be a cost effective approach to the management of the stable neutropenic patient.

Acute Disease↗

Tuberculin skin test conversion in hospital employees vaccinated with bacille Calmette-Guérin: recent Mycobacterium tuberculosis infection or booster effect?

OBJECTIVE: A rise in the incidence of purified protein derivative (PPD) skin test conversions among employees at our medical center between 1991 and 1993 prompted an examination of factors associated with PPD skin test conversion. We focused on the effect of bacille Calmette-Guérin (BCG) vaccination on PPD skin test conversion because of changes in employee health service policies in 1990 regarding testing of persons who had received BCG vaccination. METHODS: The study took place in a university teaching hospital employee health service. Charts of employees who had PPD skin test conversion (> 10 mm increase in induration of the PPD response within 2 years if younger than 35 years of age or > 15 mm if older than 35 years of age) between 1988 and 1993 were reviewed for factors that could have influenced PPD skin test conversion and compared with data from 271 randomly selected charts of employees who underwent annual employee assessments in 1993 but did not have PPD skin test conversion. RESULTS: PPD skin test conversions rose from 0.06% (1/1604) to 1.3% (22/1760; p = 0.000001) in employees tested between 1988 and 1993. Of 41 persons with PPD skin test conversion between 1991 and 1993, 29 (71%) had received BCG vaccination. Only 21% of control subjects (56/271) had received BCG vaccination (p < 0.000001 for comparison of BCG vaccination among those with PPD skin test conversion with that among control subjects). When BCG recipients were not included as having PPD skin test conversion, there was no significant increase in PPD skin test conversions. Twenty-three BCG recipients had PPD skin test conversion on their second PPD skin tests. CONCLUSION: A large proportion of PPD skin test conversions at hospitals that employ large numbers of health care workers who have received BCG vaccination may not represent recently acquired tuberculosis. Rather, these conversions may be effects of previous BCG vaccination. Two-step initial PPD skin testing may help to eliminate nearly 80% of such false-positive conversions.

Adult↗

Dermatomyositis associated with Lyme disease: case report and review of Lyme myositis.

Myositis due to the etiologic agent of Lyme disease, Borrelia burgdorferi, has been reported nine times in the English-language literature; there has been but a single report of exacerbation of dermatomyositis due to B. burgdorferi in a patient with known dermatomyositis. Multiple infectious agents, but not B. burgdorferi, have been hypothesized to trigger dermatomyositis. We report the first case of dermatomyositis that appears to have been triggered by B. burgdorferi. This case involved an individual from Westchester County, NY, who presented with skin lesions suggestive of erythema migrans and who was seropositive for Lyme disease. He soon developed a clinical syndrome suggestive of dermatomyositis: periorbital edema, dysphagia, proximal muscle weakness, and a markedly elevated level of creatine phosphokinase. We also review the clinical presentation and response to treatment of patients with Lyme myositis.

Anti-Bacterial Agents↗

Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology.

Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B. burgdorferi in patients treated early after erythema migrans. Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation. The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result. Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables. When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values. One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B. burgdorferi.

Adult↗

Demonstration of persistence of Salmonella typhimurium in an AIDS patient by molecular methods.

We document microbiological persistence of the same Salmonella typhimurium strain in an AIDS patient during 7 months of clinical observation despite prolonged quinolone therapy. Persistence was demonstrated by phage types that closely resembled one another, similar antibiotic resistance patterns, conserved restriction fragment length polymorphism of chromosomal DNA digested with different DNA restriction enzymes, identical ribotypes, and IS200 types in four characterized sequential isolates of S. typhimurium.

AIDS-Related Opportunistic Infections↗

Utility of dapsone for prophylaxis of Pneumocystis carinii pneumonia in trimethoprim-sulfamethoxazole-intolerant, HIV-infected individuals.

OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed clinically and with laboratory testing at approximately monthly intervals. RESULTS: Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up. CONCLUSION: Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

AIDS-Related Opportunistic Infections↗

Nocardiosis in patients with human immunodeficiency virus infection. Report of 2 cases and review of the literature.

Nocardia infection is a rarely reported opportunistic infection in HIV-infected patients. Nocardiosis typically occurs in HIV-infected patients with advanced immunodeficiency (89% of cases), often as the initial serious opportunistic infection (42% of cases). In most HIV-infected patients, nocardia infection is disseminated at the time of diagnosis and is characterized by an indolent course that may be difficult to differentiate from other systemic infections. Invasive procedures to obtain tissue of fluid for culture are frequently necessary to make the diagnosis, although a Gram or modified acid-fast stain of sputum or other infected material may suggest the etiologic agent. Although trimethoprim-sulfamethoxazole is the most commonly used initial therapy, it was discontinued in 50% of cases because of adverse reactions. Even though the optimal treatment has not been defined, nocardiosis in HIV-infected patients can be treated successfully with or without sulfa-containing antimicrobial regimens, along with surgical drainage when necessary. Recurrence is noted after short duration of treatment, and consideration should be given to lifelong maintenance therapy.

Acquired Immunodeficiency Syndrome↗