Intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and represent new targets for therapy.

BACKGROUND: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. METHODS: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. RESULTS: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. CONCLUSION: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.

Oral antibiotic treatment and long-term outcomes of Lyme facial nerve palsy.

PURPOSE: To study the long-term functional outcomes of patients with Lyme facial nerve palsy treated with oral antibiotics. METHODS: We conducted a retrospective double-cohort study involving patients with Lyme facial nerve palsy treated with oral antibiotics matched to three controls with early localized Lyme disease. Chart review was completed and an SF-36 health questionnaire and standardized symptom questionnaire administered. RESULTS: Lyme facial nerve palsy patients were treated with oral antibiotics for a median duration of 21 days (range 7-30 days). Only three patients underwent lumbar puncture and each demonstrated lymphocytic pleocytosis. Fourteen of 15 patients with Lyme facial nerve palsy completely regained nerve function. The long-term outcomes were similar between patients with Lyme facial nerve palsy and controls after a median follow-up duration of 4.6 years. Patients with Lyme facial nerve palsy had significantly higher reported rates of fatigue (60%) than controls (27%) (p = 0.019), but similar energy and vitality scores on the SF-36 questionnaire (55.0 vs. 58.4, p = 0.621). SF-36 social functioning domain scores were significantly lower in patients with Lyme facial nerve palsy (77.5) than in controls (88.6) (p = 0.044). There were no other significant differences noted between the two cohorts. CONCLUSIONS: For patients with Lyme facial nerve palsy in North America, treatment with oral doxycycline appears to be an effective therapeutic strategy.

Clinical features of clostridial bacteremia: a review from a rural area.

Blood samples, which were obtained from patients who lived in a rural area with approximately 500 acute-care hospital beds, were cultured from 1990 through 1997. We retrospectively reviewed the blood cultures that yielded Clostridium species (74 [0.12%] of 63,296 cultures). These were obtained from 46 different hospitalized patients (incidents per hospital, 0.03%). The source of the Clostridium species was a gastrointestinal site in 24 patients (52.2%). The most frequently identified Clostridium species was Clostridium perfringens (in 10 [21.7%] of patients), followed by Clostridium septicum (in 9 [19.6%]). Thirty-one patients (67.4%) were aged > or =65 years, 13 patients (28.3%) had diabetes mellitus, and underlying malignancy was present in 22 patients (47.8%). The mortality rate of patients whose condition had been managed surgically was 33%; for those patients whose conditions required medical management, the mortality rate was 58%. Clostridium bacteremia in these patients usually had a gastrointestinal source, it often occurred in patients with serious underlying medical conditions, and it rarely was the result of traumatic farm accidents.

Chronic sternal wound infection and endocarditis with Coxiella burnetii.

Chronic Q fever is most commonly associated with culture-negative endocarditis and less frequently with infection of vascular grafts, infection of aneurysms, hepatitis, pulmonary disease, osteomyelitis, and neurological abnormalities. We report a case of chronic sternal wound infection, polyclonal gammopathy, and mixed cryoglobulinemia in which Q fever endocarditis was subsequently diagnosed. Polymerase chain reaction analysis of the wound tissue was positive for Coxiella burnetii DNA, and treatment of the endocarditis resulted in prompt healing of the wound. Chronic Q fever can occur without epidemiological risk factors for C. burnetii exposure and can produce multisystem inflammatory dysfunction, aberrations of the immune system, and persistent wound infections.

Coinfection with Babesia microti and Borrelia burgdorferi in a western Wisconsin resident.

A 68-year-old woman, who had not traveled outside of western Wisconsin, was hospitalized after 4 weeks of chills, fevers, myalgias, neuralgias in her right arm, and pain in the right upper quadrant of her abdomen. Physical examination revealed hepatosplenomegaly, and laboratory studies showed anemia, thrombocytopenia, increased aspartate transaminase level, and microscopic hematuria. Wright's stain of a blood smear revealed intraerythrocytic organisms consistent with Babesia species. A polymerase chain reaction of whole blood specimens along with an increased serologic titer confirmed the diagnosis of Babesia microti. Indirect immunofluorescent antibody serology and Western blot analysis revealed a simultaneous infection with Borrelia burgdorferi. Coinfection with B. microti and B. burgdorferi may occur in endemic areas where both organisms are carried by the same tick vector, Ixodes scapularis. The intensity and duration of illness seem to be greatest in patients with concurrent infection.

Performance measurement in pneumonia care: beyond report cards.

OBJECTIVE: To compare the medical management of bacteremic pneumococcal pneumonia at a university-based and a community-based teaching hospital and evaluate strategies for performance measurement and subsequent improvement. DESIGN: We conducted a retrospective cohort study involving a 450-bed university hospital in the inner city and a 400-bed private hospital in a rural community. MATERIAL AND METHODS: The medical records of all adults with bacteremic pneumococcal pneumonia admitted to a university and a community hospital during a 5-year period were reviewed. Information about patient age, sex, underlying medical condition, severity of disease, health-care insurance, management, and outcome was collected and analyzed. RESULTS: Patients at the two hospitals were similar in underlying illnesses and severity of disease. In comparison with the community hospital, resource expenditure was greater at the university hospital, where all 11 identified diagnostic measures and treatment resources were used more often. This difference was statistically significant for sputum cultures, all cultures, and lumbar punctures. Despite the greater intensity of care, in-hospital mortality was higher at the university hospital (26%) than at the community hospital (12%) (P>0.1). CONCLUSION: The outcome of bacteremic pneumococcal pneumonia did not differ significantly at a university hospital in comparison with a community teaching hospital, even though resource expenditure at the university hospital was greater. Our findings suggest that hospital "report cards" based solely on outcome comparisons provide inadequate information. In contrast, examination of variations in profiles of resource utilization can detect important differences in hospitals and can be used to guide continuous quality improvement efforts and ultimately improve hospital care.

Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease.

BACKGROUND: Localized Lyme disease, manifested by erythema migrans, is usually treated with oral doxycycline or amoxicillin. Whether acute disseminated Borrelia burgdorferi infection should be treated differently from localized infection is unknown. METHODS: We conducted a prospective, open-label, randomized, multicenter study comparing parenteral ceftriaxone (2 g once daily for 14 days) with oral doxycycline (100 mg twice daily for 21 days) in patients with acute disseminated B. burgdorferi infection but without meningitis. The erythema migrans skin lesion was required for study entry, and disseminated disease had to be indicated by either multiple erythema migrans lesions or objective evidence of organ involvement. RESULTS: Of 140 patients enrolled, 133 had multiple erythema migrans lesions. Both treatments were highly effective. Rates of clinical cure at the last evaluation were similar among the patients treated with ceftriaxone (85 percent) and those treated with doxycycline (88 percent); treatment was considered to have failed in only one patient in each group. Among patients whose infections were cured, 18 of 67 patients in the ceftriaxone group (27 percent) reported one or more residual symptoms at the last follow-up visit, as did 10 of 71 patients in the doxycycline group (14 percent, P > or = 0.05). Mild arthralgia was the most common persistent symptom. Both regimens were well tolerated; only four patients (6 percent) in each group withdrew because of adverse events. CONCLUSIONS: In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline and parenterally administered ceftriaxone were equally effective in preventing the late manifestations of disease.

Clinical comparison of borreliacidal-antibody test with indirect immunofluorescence and enzyme-linked immunosorbent assays for diagnosis of Lyme disease.

OBJECTIVE: To compare the clinical results with the borreliacidal-antibody test (BAT) and two standard screening serologic tests for Lyme disease (LD)-the indirect immunofluorescence assay (IFA) and the enzyme-linked immunosorbent assay (ELISA). DESIGN: The medical records of patients from an endemic LD area, who had been serologically tested during the summer of 1992, were retrospectively categorized by clinical diagnoses without results of serologic tests. Serologic testing, which included control serum samples from patients from a nonendemic LD area, was performed in a blinded fashion, and the results were compared with the clinical categories. MATERIAL AND METHODS: Medical records of 307 patients who had been serologically tested for LD were reviewed. We found untreated, active LD in 43 patients (early-localized LD, 21; early-disseminated LD, 14; and late-disseminated LD, 8) and treated LD in 33. Non-LD cases were categorized into acute or chronic conditions of unknown or known cause. RESULTS: Overall, the BAT had a sensitivity of 11% in active LD and did not correlate with results of other conventional surface antibody assays. The IFA and ELISA were more sensitive (67 to 93%), but false-positive results frequently were noted (20 to 40%) in acute and chronic non-LD inflammatory conditions. The specificity of the BAT, IFA, and ELISA in the control group was 96%, 93%, and 97%, respectively. CONCLUSION: Until the sensitivity, as measured by prospective clinical studies, is improved without loss of specificity, the BAT should not be used clinically for the diagnosis of LD. Suspected cases of LD with atypical clinical manifestations should have positive ELISA and IFA results confirmed with a standardized immunoblot assay.

Subclavian hemodialysis catheter infections: a prospective, randomized trial of an attachable silver-impregnated cuff for prevention of catheter-related infections.

OBJECTIVE: To determine if an attachable silver-impregnated cuff is effective in reducing subclavian hemodialysis catheter-related infections. DESIGN: Prospective, randomized, nonblinded study. SETTING: Community teaching hospital. PATIENTS: One hundred one acute and chronic renal failure patients requiring subclavian venipuncture and catheterization. After randomization, 47 patients underwent subclavian catheterization with a silver-impregnated cuff (Ag-CC), and 54 patients had routine catheter (RC) placements. MEASUREMENTS: Multiple presumed predictor variables for catheter-related infections, exit site infection rate, bacteremia rates, and semiquantitative cultures of all catheters.

Babesiosis in Wisconsin: a potentially fatal disease.

Babesiosis is emerging as an important tick-borne zoonosis in the United States. Most reported cases of this parasitic disease have been acquired in the Northeast. To date, only two clinical cases of Babesia microti infection acquired in the upper Midwest have been described. We report eight more cases. Most if not all of the 10 total cases probably were acquired in northwestern Wisconsin. Three cases (30% of 10) we now report were fatal and occurred in elderly patients (65-75 years old) who died after complicated hospital courses. One patient probably had had a latent Babesia infection that activated because of immunosuppression attributable to high-dose corticosteroid therapy and to splenic infarctions caused by cholesterol emboli. All three fatal cases were diagnosed incidentally and highlight the importance of considering the diagnosis of babesiosis in febrile patients who have been in babesiosis-endemic areas; examining their blood smears carefully; and treating promptly with clindamycin and quinine, and, if indicated, exchange transfusion. Medical personnel should be knowledgeable about this zoonosis, which is not limited to the northeastern United States, and is potentially serious, sometimes fatal.

Pseudomonas aeruginosa infections of intact skin.

Pseudomonas aeruginosa infections of healthy skin are uncommon. We report four cases of P. aeruginosa infections of intact skin. These cases illustrate the clinical spectrum of these cutaneous infections: localized, mild epidermal infections (the green nail syndrome and webbed space infections), moderately serious infections (cutaneous folliculitis and otitis externa), and, in immunocompromised patients, extremely serious infections (malignant otitis externa, perirectal infection, and ecthyma gangrenosum).

Subcutaneous alternariosis of the foot in a patient on corticosteroids.

To the authors' knowledge, this is the first reported case of alternariosis involving the subcutaneous tissues of the foot. Podiatrists are likely to see more of this condition and other unusual fungi causing deep foot infections in the future because of the increasing population of immunocompromised patients.

In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone.

We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins. MICs for B. burgdorferi 297 were 23 micrograms/ml (cephalexin), 45 micrograms/ml (cefadroxil), 91 micrograms/ml (cefaclor), 0.13 microgram/ml (cefuroxime), 0.8 microgram/ml (cefixime), and 0.02 microgram/ml (ceftriaxone). When B. burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms.