Molecular detection and quantification of pertussis and correlation with clinical outcomes in children

Pertussis is an under-recognized serious infection. Conventional cultures are insensitive and of limited utility after antibiotic exposure. We corroborated the utility of real-time polymerase chain reaction (PCR) as a diagnostic tool in pertussis and investigated its role as a prognostic tool by evaluating its benefit in the quantification of pertussis bacterial load. All pertussis-positive PCR tests (n = 104) submitted over 5 years were collected for retrospective study. PCR cycle threshold was compared to quantitative culture in 43. Compared to PCR, the sensitivity of culture was 41%. Our PCR assay reliably quantified bacterial load and was quantitatively reproducible. Higher bacterial load correlated with longer duration of hospitalization (P = 0.0003), and multivariate logistic regression models demonstrated this association to be independent. The study confirmed PCR as a superior diagnostic tool in pertussis. PCR quantification of bacterial load at initial diagnosis predicts later clinical disease severity, suggesting a potential benefit of PCR as a prognostic tool in pertussis.     

Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models

PURPOSE: The purpose of this study was to characterize the activity of the Bcl-2 protein family inhibitor ABT-263 in a panel of small cell lung cancer (SCLC) xenograft models. EXPERIMENTAL DESIGN: A panel of 11 SCLC xenograft models was established to evaluate the efficacy of ABT-263. Single agent activity was examined on a continuous dosing schedule in each of these models. The H146 model was used to further evaluate dose and schedule, comparison to standard cytotoxic agents, and induction of apoptosis. RESULTS: ABT-263 exhibited a range of antitumor activity, leading to complete tumor regression in several models. Significant regressions of tumors as large as 1 cc were also observed. The efficacy of ABT-263 was also quite durable; in several cases, minimal tumor regrowth was noted several weeks after the cessation of treatment. Antitumor effects were equal or superior to that of several clinically approved cytotoxic agents. Regression of large established tumors was observed through several cycles of therapy and efficacy was retained in a Pgp-1 overexpressing line. Significant efficacy was observed on several dose and therapeutic schedules and was associated with significant induction of apoptosis. CONCLUSIONS: ABT-263 is a potent, orally bioavailable inhibitor of Bcl-2 family proteins that has recently entered clinical trials. The efficacy data reported here suggest that SCLC is a promising area of clinical investigation with this agent.     

D-dimer and calf circumference in the evaluation of outpatient deep venous thrombosis

OBJECTIVE: Duplex ultrasonography (DU) is the primary method for diagnosis of deep venous thrombosis (DVT) but is relatively expensive and not always readily available. Attempts to exclude the diagnosis of DVT with D-dimer or clinical criteria independently have been unsuccessful. The goal of our study was to evaluate a second-generation rapid quantitative D-dimer and simple clinical parameters for screening of outpatients for DVT. Patients and Methods: Patients undergoing DU of the lower extremities for suspected DVT were prospectively evaluated. Patients undergoing lower extremity venous ultrasound scan for suspected pulmonary embolism or already on anticoagulant therapy were excluded from the study. Data were analyzed to assess the optimal combination of characteristics to include and exclude proximal DVT. RESULTS: One hundred fifty-six outpatients met inclusion criteria and were enrolled in the study. Elevated levels of D-dimer of 0.5 ng/mL or more were noted in 21 of 22 patients diagnosed with DVT, yielding a sensitivity of 95% and negative predictive value of 99%. Subjective symptoms of swelling or pain were present in 94% of all outpatients. Asymmetric calf swelling of more than 2.0 cm was noted in 14 of 22 patients (64%) with proximal DVT compared with 22 of 134 patients (16%) without DVT (P <.003). No single clinical history variable was significant on multivariate analysis. All outpatients with proximal DVT had either leg swelling of more than 2 cm or a positive D-dimer. CONCLUSION: A combination of a second-generation quantitative D-dimer and calf measurement provides an easy and effective means of excluding proximal DVT when screening outpatients. Patients with calf circumference 2.0 cm or less and a negative D-dimer may undergo nonemergent DU. Patients with a positive D-dimer or asymmetrical calf swelling of more than 2.0 cm alone or in combination should undergo emergent DU.     

Laparoscopic splenectomy: analysis of 60 consecutive cases

The purpose of the study was to analyze the results of 60 patients who were candidates for laparoscopic splenectomy. Over the period from May 1994 to May 2001, 60 patients were candidates for splenectomy. Laparoscopy was contraindicated in 3 cases because of ASA III and marked splenomegaly (2 cases) and previous gastric resection (1 case). The procedure was indicated for benign disease in 38 cases and for malignant disease in the remainder. Fifty-three procedures were completed laparoscopically (92.9%). Conversion proved necessary in 4 patients (6.7%) due to large incisional hernia, perisplenic abscess, bleeding of major splenic vessels at the hilum and marked splenomegaly (2 cases of lymphoma). The mean operative time was 200 min for the malignancies and 110 min for the benign conditions (P < 0.05). Major morbidity occurred in 5 cases (8.7%). No deaths were registered. The mean postoperative hospital stay was 7.5 days for patients with malignancies and 5.2 days for patients with benign disease (P < 0.05). Laparoscopic splenectomy was safe and effective in patients with benign disease, even in cases of marked splenomegaly. The morbidity rate was significantly higher in lymphoma patients than in patients with benign haematological disorders.     

Changes in fetal acid-base chemistries following tromethamine (THAM) or bicarbonate infusions into fetal circulation of amniotic fluid

Direct infusions of equimolar quantities of bicarbonate and tromethamine into rhesus monkey fetal circulation near term resulted in roughly equivalent increases in fetal pH. However, intra-amniotic infusion of tromethamine was not followed by alkaline changes in the fetus and in most instances was followed by a progressive fetal acidosis. This sharply contrasts with previous experimental success in elevating fetal pH via amniotic fluid bicarbonate infusions.     

Women's decision-making roles regarding contralateral prophylactic mastectomy

BACKGROUND: Contralateral prophylactic mastectomy (CPM) is the removal of a nonaffected breast in a woman with unilateral breast cancer and is effective in reducing the risk of recurrences. Little is known about women's decision-making roles regarding CPM. METHODS: Women aged 18-80 years with CPM performed at one of six health maintenance organizations between 1979 and 1999 were surveyed. We determined women's reported decision-making roles at the time of CPM, analyzed their trends over time, and explored the association between decision-making roles and psychosocial outcomes following CPM. RESULTS: We received 562 responses (response rate = 73%); 431 completed items needed for this analysis. Most respondents were white, younger than 55 years at CPM, married, and had CPM within 10 years of completing the survey. Forty-five percent made the decision to undergo CPM alone, 37% considered their doctor's opinion, 15% shared the decision with their doctor and only 3% reported their doctor primarily made the decision. Women reporting active roles were more likely to be younger (P<.0008), college educated (P<.0001) and have CPM more recently (P = .002). Compared with those sharing the decision with their doctors, women with active roles were twice as likely to be satisfied 6 months following CPM (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.1 to 4.2) and report current concern about breast cancer (OR = 1.9, 95% CI = 1.0 to 3.4). CONCLUSIONS: Most women reported active or shared roles in decision making regarding CPM, particularly younger women, those with college education, and those with recent CPM. Women with active roles were more often satisfied in the short term but were also more likely to report current concern about breast cancer. Whether higher concern is related to insufficient input from clinicians should be explored. Prospective data are needed.     

Complications following bilateral prophylactic mastectomy

BACKGROUND: Bilateral prophylactic mastectomy significantly decreases breast cancer risk, but complications of the procedure have only been described in single-site studies. We describe the frequency and type of complications in women who underwent bilateral prophylactic mastectomy in a multisite community-based cohort. METHODS: Women aged 18-80 years undergoing bilateral prophylactic mastectomy without a personal history of breast cancer at one of six health plans were eligible. We identified women from automated data sources, then reviewed hospital data, ambulatory notes, and other chart elements to confirm eligibility and obtain all charted information about complications and surgeries performed after prophylactic mastectomy, including reconstructive procedures. Reconstructions were characterized by type (implant vs. tissue graft). Complications were noted for a 1-year period after any surgical procedure. RESULTS: We identified 269 women with prophylactic mastectomy who were followed for a mean of 7.4 years. Their mean age was 44.9 years. Nearly 80% undertook reconstruction, most with prosthetic implants. One or more complications occurred in 64%. The most common complications were pain (35% of women), infection (17%), and seroma (17%). Women with no reconstruction had fewer complications (mean of .93) than women who had implant (2.0) or tissue graft (2.4) reconstruction procedures (differences from no reconstruction: 1.07 [95% confidence interval = 0.36 to 1.77] and 1.50 [95% confidence interval = 0.44 to 2.56] respectively). Delay of reconstruction after mastectomy was associated with a borderline-significant higher risk of complications (80.6%) compared to simultaneous reconstruction (64.0%, P = .055). CONCLUSION: We found that almost two-thirds of women undergoing bilateral prophylactic mastectomy had at least one complication following surgery. Further work should be done to minimize and to understand the effect of complications of bilateral prophylactic mastectomy.