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Biomedical subjects

Matthew J Hepburn

Publications and source records attributed to Matthew J Hepburn.

17 recordsLinked to original sources

Live vaccine strain Francisella tularensis is detectable at the inoculation site but not in blood after vaccination against tularemia.

INTRODUCTION: Live vaccine strain (LVS) Francisella tularensis is a live, attenuated investigational tularemia vaccine that has been used by the US Army for decades to protect laboratory workers. Postvaccination bacterial kinetic characteristics of LVS at the inoculation site and in the blood are unknown and, therefore, were assessed in a prospective study. LVS vaccination of laboratory workers provided the opportunity to compare culture with polymerase chain reaction (PCR) for the detection of F. tularensis in human clinical samples. METHODS: Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls) and at 5 specified time points (days 1, 2, 7 or 8, 14 or 15, and 35 after vaccination). Bacterial culture and PCR of whole blood samples (17 volunteers) and inoculation site swabs (41 volunteers) were performed. RESULTS: The culture and PCR results of all blood samples were negative. Results of real-time PCR from the inoculation site samples were positive for 41 (100%) of 41 volunteers on day 1, for 40 (97.6%) of 41 volunteers on day 2, for 24 (58.5%) of 41 on day 7 or 8, for 6 (16.7%) of 36 on day 14 or 15, and for 0 (0%) of 9 on day 35. Positive results of bacterial cultures of the inoculation site samples occurred significantly less frequently, compared with PCR testing, with 4 (9.8%) of 41 volunteers having positive results on day 1 (P<.001) and 4 (9.8%) of 41 on day 2 (P<.001); all results from subsequent days were negative. CONCLUSIONS: F. tularensis LVS genomic DNA was detected in the majority of samples from the inoculation site up to 1 week after LVS vaccination, with real-time PCR being more sensitive than culture. Our data suggest that bacteremia does not occur after LVS vaccination in normal, healthy human volunteers.

Adult↗

Outcomes of community-acquired, methicillin-resistant Staphylococcus aureus, soft tissue infections treated with antibiotics other than vancomycin.

Community-acquired, methicillin-resistant Staphylococcus aureus (cMRSA), soft tissue infections are becoming increasingly prevalent in the outpatient setting. Few studies have been specifically designed to examine the efficacy of oral antibiotic therapy for these infections. We performed an observational study to determine the effect of alternative, orally administered antibiotics on cMRSA soft tissue infections. Consecutive patients between January 2001 and March 2004 who had skin or soft tissue infections from which cMRSA was isolated and who had never received vancomycin were studied through retrospective and concurrent review. Primary outcome measures were improvement or resolution of infection 5 and 14 days after initiation of treatment with orally administered antibiotics and rates of recurrence within 30 days after completion of treatment. Thirty subjects met the inclusion criteria. Twenty-one subjects received either clindamycin, trimethoprim/sulfamethoxazole, doxycycline/minocycline, or a fluoroquinolone. Five subjects received a beta-lactam antibiotic with abscess drainage, and four subjects underwent abscess drainage alone. Improvement was noted for all subjects at 5 days, complete resolution of infection occurred for all subjects by 14 to 17 days, and in no case did relapse occur within 30 days. cMRSA skin and soft tissue infections can be successfully treated with orally administered antibiotics to which the organism has demonstrable in vitro susceptibility.

Adolescent↗

The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: a retrospective observational study.

BACKGROUND: Steatosis is occasionally reported during screening ultrasonography in patients with hepatitis C virus (HCV). We conducted a retrospective observational study to assess the factors associated with steatosis on ultrasonography and the relationship between steatosis on ultrasound versus biopsy in patients infected with HCV in a clinical setting. Our hypothesis was ultrasonography would perform poorly for the detection of steatosis outside of the context of a controlled study, primarily due to false-positive results caused by hepatic fibrosis and inflammation. METHODS: A retrospective review of ultrasound reports was conducted on patients infected with HCV in a tertiary care gastroenterology clinic. Reports were reviewed for the specific documentation of the presence of steatosis. Baseline clinical and histologic parameters were recorded, and compared for patients with vs. without steatosis. Multiple logistic regression analysis was performed on these baseline variables. Liver biopsies were reviewed by two pathologists, and graded for steatosis. Steatosis on biopsy was compared to steatosis on ultrasound report, and the performance characteristics of ultrasonography were calculated, using biopsy as the gold standard. RESULTS: Ultrasound reports were available on 164 patients. Patients with steatosis on ultrasound had a higher incidence of the following parameters compared to patients without steatosis: diabetes (12/49 [24%] vs. 7/115 [6%], p < 0.001), fibrosis stage > 2 (15/48 [31%] vs. 16/110 [15%], p = 0.02), histologic grade > 2 (19/48 [40%] vs. 17/103 [17%], p = 0.002), and ALT (129.5 +/- 89.0 IU/L vs. 94.3 +/- 87.0 IU/L, p = 0.01). Histologic grade was the only factor independently associated with steatosis with multivariate analysis. When compared to the histologic diagnosis of steatosis (n = 122), ultrasonography had a substantial number of false-positive and false-negative results. In patients with a normal ultrasound, 8/82 (10%) had > 30% steatosis on biopsy. Among patients with steatosis reported on ultrasound, only 12/40 (30%) had > 30% steatosis on biopsy review. CONCLUSION: Steatosis on ultrasound is associated with markers of inflammation and fibrosis in HCV-infected patients, but does not consistently correlate with steatosis on biopsy outside of the context of a controlled study. Clinicians should be skeptical of the definitive diagnosis of steatosis on hepatic ultrasonography.

Adult↗

Seroprevalence of hepatitis C and associated risk factors among an urban population in Haiti.

BACKGROUND: The seroprevalence of hepatitis C varies substantially between countries and geographic regions. A better understanding of the seroprevalence of this disease, and the risk factors associated with seropositive status, supply data for the development of screening programs and provide insight into the transmission of the disease. The purpose of this investigation was to determine the seroprevalence of hepatitis C and associated risk factors in an urban population in Haiti. METHODS: A prospective survey for hepatitis C antibodies was conducted among an urban outpatient population in Cap-Haitien, Haiti, with a sample size of 500 subjects. An anonymous 12 question survey, with inquiries related to demographic characteristics and risk factors for HCV acquisition, was concomitantly administered with testing. These demographic and behavioral risk factors were correlated with HCV antibody status using univariate and multivariate tests. RESULTS: The prevalence of positive HCV antibody was 22/500 (4.4%). Subjects that were anti-HCV positive had an average of 7 +/- 8.6 lifetime sexual partners, compared to average of 2.5 +/- 3.5 lifetime sexual partners among HCV-negative subjects (p = 0.02). In a multiple logistic regression model, intravenous drug use (OR 3.7, 1.52-9.03 95% CI) and number of sexual partners (OR 1.1, 1.04-1.20 95% CI) were independently associated with a positive HCV antibody result. CONCLUSIONS: A substantial number of subjects with HCV antibodies were detected in this population in Haiti. Further investigation into the correlation between the number of sexual partners and testing positive for hepatitis C antibodies is indicated.

Adult↗

Differences in treatment outcome for hepatitis C among ethnic groups.

BACKGROUND: Studies of interferon-based therapies for hepatitis C virus (HCV)-infected patients have documented variable response rates according to ethnicity. However, these studies enrolled low numbers of ethnic minorities. METHODS: Data from two multicenter trials of combination therapy for hepatitis C were analyzed to determine predictors of treatment success. The first trial was a randomized study comparing interferon administered three times weekly with daily administration. Patients in both interferon groups received weight-based ribavirin. The second trial was an observational study of daily interferon and ribavirin. Only treatment-naïve patients were included in the analysis. Ethnicity (used as a nonspecific term to include race) was determined by patient self-report. Sustained virologic response was defined as negative HCV RNA by polymerase chain reaction at 24 weeks after completion of therapy. RESULTS: A total of 661 patients (390 from the randomized trial and 271 from the observational trial) were available for analysis. Sustained virologic response was highest among Asians (61% [22/36]), followed by whites (39% [193/496]), Hispanics (23% [18/79]), and African Americans (14% [7/50]). In a multiple logistic regression model that adjusted for other factors known to affect treatment outcome, including hepatitis C genotype, Asians continued to be more likely to respond to treatment, whereas Hispanics and African Americans were less likely, as compared with whites. CONCLUSION: Sustained response rates to interferon and ribavirin therapy differ among ethnic groups. Ethnicity appears to be associated with treatment outcomes, even in a model that adjusts for other factors that influence response to therapy.

Adult↗

Frequency of vaccinia virus isolation on semipermeable versus nonocclusive dressings covering smallpox vaccination sites in hospital personnel.

BACKGROUND: The Centers for Disease Control and Prevention recommends a semipermeable occlusive dressing for hospital workers who receive smallpox vaccination. OBJECTIVE: The study was designed to determine the frequency of vaccinia virus isolation from the outer surface of semipermeable dressings and to compare the prevalence of vaccinia virus on the outer surface of semipermeable dressings with its prevalence on the outer surface of nonocclusive dressings. METHODS: A prospective, observational study was conducted on hospital employees who received smallpox vaccination at a military academic medical center. Subjects were instructed to wear a semipermeable dressing if they had direct patient contact. Employees without direct patient care had the option of wearing a semipermeable dressing or a nonocclusive dressing. Prior to a programmed dressing change, the outer surface of the bandage site was swabbed and cultured for virus. Samples were considered positive when cytopathic effects were observed, with results confirmed as vaccinia by polymerase chain reaction. RESULTS: A total of 212 cultures were obtained from 93 subjects. All cultures directly obtained from active lesions were positive (13/13). Positive cultures were obtained from 7% (10/135) of the semipermeable dressings and 23% (15/64) of the nonocclusive dressings (P <.05). Ten percent (8/79) of the semipermeable dressings with purulent exudate observed underneath the bandage were culture positive, compared with 4% (2/56) of semipermeable dressings with no purulent exudate observed underneath the bandage (P=.19). CONCLUSIONS: Compared with nonocclusive dressings, the semipermeable dressing reduced, but did not eliminate, the frequency with which vaccinia virus was cultured from the surface of the dressing. Virus was present, but only rarely, on the dressing surface in the absence of purulent exudate under the semipermeable dressings.

Bandages↗

The effect of semipermeable dressings on smallpox vaccine site evolution.

BACKGROUND: Many hospital systems in the United States are contemplating the implementation of a smallpox vaccination program. The Centers for Disease Control and Prevention and other organizations recommend use of occlusive dressings over the vaccination site of health care workers in contact with patients. Minimal data are available on the impact of an occlusive dressing on the evolution of the vaccinia inoculation site. METHODS: We conducted a prospective observational study in which subjects were instructed to cover their vaccination site with either a semipermeable dressing over gauze or gauze alone. We recorded the duration of semipermeable dressing use and parameters pertaining to vaccination site evolution, to include time until scab separation. RESULTS: The increased use of a semipermeable dressing is associated with increased time until scab separation (n = 41, r =.48, P =.001 by regression analysis). This analysis predicts a 9-day difference in time until scab separation between patients that wore semipermeable dressings 100% of the time versus not at all. No significant correlation was observed between semipermeable dressing use and size of maximum erythema, time until maximum erythema, size of erythema on day 6 or 8, nor time until pustule formation. CONCLUSION: Semipermeable dressing use appears to prolong the time until scab separation and possibly the duration of infectivity and risk of secondary transmission. Health care organizations may wish to consider this information when instituting a smallpox vaccination program.

Adult↗

A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy.

OBJECTIVES: To evaluate the effects of recombinant human interleukin (rhIL)-11 on liver histology in patients with chronic hepatitis C virus (HCV) infection and advanced liver disease who had failed antiviral therapy. METHODS: This was an open-label study of rhIL-11 (Neumega), Wyeth Laboratories, Collegeville, PA) at a dose of 5 microg/kg administered by subcutaneous injection daily for 12 wk. The primary efficacy endpoint was the change in the Knodell Histology Activity Index (HAI) between pre- and posttreatment liver biopsies. Secondary efficacy endpoints included changes in plasma alanine transaminase (ALT) concentrations and in the number of platelets. RESULTS: The Knodell HAI improved in 11 (55%) of the 20 subjects enrolled, with the mean score improving from 7.3 to 5.9 (p= 0.006). Eight subjects (40%) experienced significant improvement as defined by a decrease of at least two points in the HAI. IL-11 treatment was also associated with a decrease in ALT levels from a mean level of 113 IU/L at baseline to 65 IU/L at week 12 (p < 0.001). Platelet levels increased from a mean of 143 x 10(3)/microl at baseline to 198 x 10(3)/mul at week 12 of treatment (p < 0.001). Overall, rhIL-11 was well tolerated and no serious adverse events (AEs) were reported. The most common AE was edema of the lower extremities, which occurred in all subjects. CONCLUSIONS: The findings from this pilot study suggest that rhIL-11 may be beneficial for patients with hepatic inflammation and advanced liver disease associated with chronic HCV infection. Larger clinical trials are warranted to further evaluate the long-term antiinflammatory and antifibrotic effects of rhIL-11.

Adult↗

Low serum vitamin B12 levels in an outpatient HIV-infected population.

A retrospective review was conducted on serum vitamin B12 levels in an HIV-infected outpatient cohort, many of whom received antiretroviral therapy. B12 levels were obtained at most staging visits (every six months) and when clinically indicated. For each serum B12 level, laboratory values and clinical symptoms were recorded. Thirty-two patients (32/251 or 13%) had at least one low B12 level (<211pg/mL) during the course of their HIV infection. Within two years of their initial HIV presentation, 6/57 patients had a low serum B12. Using multiple linear regression analysis, a higher serum B12 level was significantly associated with higher folate levels, African-American race, and lower mean corpuscular volume. B12 levels increased significantly after initiating antiretroviral therapy (416 vs 535 pg/mL, P=0.04). In conclusion, low serum B12 levels occur commonly among HIV-infected patients, even at early stages without overt symptoms of B12 deficiency. Antiretroviral therapy may increase serum B12 levels.

Adult↗

Septic arthritis caused by Granulicatella adiacens: diagnosis by inoculation of synovial fluid into blood culture bottles.

Granulicatella species, formerly known as nutritionally variant streptococci, cause a variety of infections, primarily endocarditis. We report the first culture-proven case of a Granulicatella species causing septic arthritis. A 68-year-old female presented with knee pain and swelling. She was initially evaluated with arthrocentesis and arthroscopy, but no organism was identified. Her pain improved after a brief course of antibiotics but recurred 3 months later. She underwent repeat arthrocentesis, with direct inoculation of synovial fluid into blood culture bottles. Granulicatella adiacens was recovered from both bottles. She was treated with cefazolin for 4 weeks combined with gentamicin for the first 2 weeks. Her knee pain and swelling resolved without evidence of recurrence. Granulicatella should be considered in cases of septic arthritis with initially negative synovial fluid cultures. Inoculation of blood cultures bottles with synovial fluid may increase the diagnostic yield for these species.

Aged↗

Increasing resident research in a military internal medicine program.

The internal medicine residents from our training program rarely participated in scholarly activity prior to 1994. In an attempt to increase the quality and quantity of resident research, we initiated a research program that included: (1) a mandatory research project, (2) 2 months of dedicated research time, (3) appointment of a research director, (4) lectures on the critical appraisal of medical literature and research design, (5) technical support, (6) faculty mentoring, (7) a research meeting and competition involving five residency programs, and (8) military achievement awards. From 1994 to 1999, our house staff has had 134 research presentations and 21 manuscripts accepted for publication in peer-reviewed journals. Ninety percent of our residents presented at least one project at a scientific meeting by completion of their training between 1996 and 1999. Resident scholarly activity is significantly enhanced by a structured research program, an opportunity to present at a scientific meeting, and award recognition.

Humans↗

Pertussis in a military and military beneficiary population: case series and review of the literature.

Three cases of pertussis (whooping cough) identified in a military emergency department are reported. Two of these cases involved infants with typical presentations. One of these infants was too young to have received immunizations, and the other child was only partially immunized. The third case involved an active duty soldier with a chronic cough. Pertussis has become increasingly important as a cause of chronic cough in adults. As a result of the infectivity of this organism, close-quarter situations, such as day care centers and military barracks, create the opportunity for substantial person-to-person transmission. Typical and atypical clinical presentations of pertussis are discussed, with an emphasis on currently available diagnostic modalities. The epidemiology and pathophysiology of this disease are also reviewed. The medical management of active duty soldiers and their dependents (both pediatric and adult) with this largely underappreciated infection and their close contacts is presented.

Adult↗

Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis.

BACKGROUND: Cellulitis is a condition routinely encountered in the primary care setting. No previous study has compared a short (5 days) vs standard (10 days) course of therapy of the same antibiotic in patients with uncomplicated cellulitis. METHODS: We performed a randomized, double-blind, placebo-controlled trial to determine if 5 days of therapy has equal efficacy to 10 days of therapy for patients with cellulitis. Of 121 enrolled subjects evaluated after 5 days of therapy for cellulitis, 43 were randomized to receive 5 more days of levofloxacin therapy (10 days total antibiotic treatment), and 44 subjects to receive 5 more days of placebo therapy (5 days of total antibiotic treatment). Levofloxacin was given at a dose of 500 mg/d. Subjects were not randomized if they had worsening cellulitis, a persistent nidus of infection, a lack of any clinical improvement, or abscess formation within the first 5 days of therapy. The main outcome measure was resolution of cellulitis at 14 days, with absence of relapse by 28 days, after study enrollment. RESULTS: Eighty-seven subjects were randomized and analyzed by intention to treat. There was no significant difference in clinical outcome between the 2 courses of therapy (success in 42 [98%] of 43 subjects receiving 10 days of antibiotic, and 43 [98%] of 44 subjects receiving 5 days of antibiotic) at both 14 and 28 days of therapy. CONCLUSION: In patients with uncomplicated cellulitis, 5 days of therapy with levofloxacin appears to be as effective as 10 days of therapy.

Analysis of Variance↗