Inhomogeneity of ventilation leads to unpredictable errors in measured D(L)CO

We evaluated the effects of inhomogeneity of ventilation on single-breath (SB), rebreathing (RB) and open circuit (OC) D(L)CO using a mathematical model consisting of two alveolar compartments and a common dead space. Inhomogeneity in ventilation was studied by altering inspired volume, initial alveolar volume and compartment size independently. When distribution of inspired volume between alveolar compartments was inhomogeneous (9:1), D(L)CO was underestimated by 35% for SB, 25% for RB, and 16% for OC, and there was an underestimation in V(A) of 9%, 15% and 9%, respectively. With inhomogeneity in initial alveolar volume there was an overestimation in D(L)CO of 13%, 7% and 11% for SB, RB and OC techniques and an underestimation of V(A) of 7%, 12% and 9%. Finally inhomogeneity of compartment size led to an underestimation of D(L)CO of 18%, 35% and 36% with no change in measured V(A). These results suggest D(L)CO measurements are sensitive to inhomogeneity of ventilation, and importantly, all techniques were at times, significantly in error.     

Interlaboratory reliability of Hybrid Capture 2

We evaluated the interlaboratory reproducibility of the Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD), a test for oncogenic human papillomavirus (HPV) DNA, using data from 4 clinical center (CC) laboratories and the quality control (QC) laboratory participating in the ASCUS (atypical squamous cells of undetermined significance) and LSIL (low-grade squamous intraepithelial lesion) Triage Study (ALTS). Residual liquid cytology specimens were tested routinely throughout the duration of ALTS at CC laboratories, and a stratified (by time in the study) random sample of specimens was retested by the HPV QC laboratory using equivalent protocols. Of the specimens selected (N = 1,175, 5.50% of all specimens obtained), 1,072 (91.23%) had sufficient specimen volume for retesting. The kappa value between all CC laboratories and the HPV QC laboratory was 0.84 (95% confidence interval, 0.78-0.89), with kappa values for individual CCs and the HPV QC laboratory ranging from 0.79 to 0.89. Agreement between test results was lowest among results for women with negative cytologic findings (0.73); among those with equivocal or abnormal cytologic findings, kappa values were 0.80 or more. These data show that HC2 is a reliable test for detecting clinically relevant oncogenic HPV DNA.     

Is cidofovir a useful adjunctive therapy for recurrent respiratory papillomatosis in children?

OBJECTIVE: To assess the usefulness of cidofovir in treating recurrent respiratory papillomatosis in children. Cidofovir is an acyclic nucleoside phosphonate that has been reported to be effective in the treatment of respiratory papillomatosis in several small series of patients. METHODS: A prospective study was conducted in 11 children (mean, 2.1 years; range, 0.5-3 years at diagnosis) with recurrent respiratory papillomatosis who at the start of the study were requiring debridement of papillomas at least every 6 weeks. After microlaryngoscopy with powered microdebridement of papillomas patients received intralesional injection of cidofovir (5mg/ml). The severity of papillomatosis was rated at each visit using a standardized papilloma severity scoring system. The success of therapy was measured by the trend in the patient's papilloma severity scores before and after cidofovir therapy and by whether the frequency of operative interventions decreased in the period after treatment began. RESULTS: Three patients had impressive improvements in severity scores and a decrease in the frequency of required operative interventions after cidofovir, two patients had a partial response, and for six patients cidofovir was considered ineffective. CONCLUSIONS: Intralesional cidofovir did not decrease the severity or frequency of operative intervention for recurrent respiratory papillomas in the majority of children in this study. The drug did improve papillomatosis in the minority of patients without causing notable morbidity. A large multi-institutional controlled study is needed to better assess the efficacy of this treatment.     

Fraction of free-base nicotine in fresh smoke particulate matter from the Eclipse "cigarette" by 1H NMR spectroscopy

Solution 1H NMR (proton-NMR) spectroscopy was used to measure the distribution of nicotine between its free-base and protonated forms at 20 degrees C in (a) water; (b) glycerin/water mixtures; and (c) puff-averaged "smoke" particulate matter (PM) produced by the Eclipse cigarette, a so-called "harm reduction" cigarette manufactured by R. J. Reynolds (RJR) Tobacco Co. Smoke PM from the Eclipse contains glycerin, water, nicotine, and numerous other components. Smoke PM from the Eclipse yielded a signal for the three N-methyl protons on nicotine at a chemical shift of delta (ppm) = 2.79 relative to a trimethylsilane standard. With alpha fb = fraction of the total liquid nicotine in free-base form, and alpha a = fraction in the acidic, monoprotonated NicH+ form, then alpha a + alpha fb approximately 1. (The diprotonated form of nicotine was assumed negligible.) When the three types of solutions were adjusted so that alpha a approximately 1, the N-methyl protons yielded delta a = 2.82 (Eclipse smoke PM); 2.79 (35% water/65% glycerin); and 2.74 (water). When the solutions were adjusted so that alpha fb approximately 1, the N-methyl protons yielded delta fb = 2.16 (Eclipse smoke PM); 2.13 (35% water/65% glycerin); and 2.10 (water). In all of the solutions, the rate of proton exchange between NicH+ and Nic was fast relative to the 1H-NMR chemical shift difference in hertz. Each solution containing both NicH+ and Nic thus yielded a single N-methyl peak at a delta given by delta = alpha a delta a + alpha fb delta fb so that delta varied linearly between delta a and delta fb. Since alpha fb = (delta a-delta)/(delta a-delta fb), then delta = 2.79 for the unadjusted Eclipse smoke PM indicates alpha fb approximately 0.04. The effective pH of the Eclipse smoke PM at 20 degrees C may then be calculated as pHeff = 8.06 + log[alpha fb/(1-alpha fb)] = 6.69, where 8.06 is the pKa of NicH+ in water at 20 degrees C. The measurements obtained for the puff-averaged Eclipse smoke PM pertain to the chemistry of the smoke PM as it might be initially inhaled at 20 degrees C. Upon inhalation, the volatilization of nicotine and other acid/base active compounds (as well as a warming toward a body temperature of 37 degrees C) will alter the pHeff value of the smoke PM during the time that it resides and ages in the respiratory tract.     

A novel model of pneumonia from intraperitoneal injection of bacteria

BACKGROUND: Pneumonia remains a major clinical problem in the surgical patient. Experimental modeling by intratracheal injection of bacteria is not consistently reproducible. In an attempt to produce peritonitis by Klebsiella, we found evidence of pneumonia on autopsy and further developed this approach as a new experimental model. METHODS: Male Swiss Webster mice were given intraperitoneal (IP) injections of Klebsiella pneumoniae serotype 2 in different doses and this was compared with similar doses given intravenously (IV). A dose dependent survival curve was generated. Subsequently, 10(3) colony forming units (CFU) of bacteria were used in further experiments. Blood, peritoneal fluid and lung tissue were collected at time points up to 72 hours after injection and were cultured for levels of bacteria. Lung weights and myeloperoxidase levels were also measured. RESULTS: Intraperitoneal administration of Klebsiella was uniformly lethal with as few as 10(2) bacteria. Lung weight increased after IP Klebsiella, and all animals became bacteremic within 24 hours correlating with high bacterial levels in the lung. Conversely, most animals (72%) survived IV injection of bacteria, and were able to clear bacteria from the blood and lung. CONCLUSIONS: We found that this model produced no clinically apparent peritonitis after 48 hours, but uniformly resulted in histopathologic changes of pneumonia by 24 hours. Survival time was related to initial dose of Klebsiella and there was a linear correlation between bacterial levels in the blood and lung. This model is reproducible, simple to perform, and the severity is easy to manipulate.     

Effects of adjunctive Swedish massage and vibration therapy on short-term postoperative outcomes: a randomized,controlled trial

OBJECTIVE: To examine the effects of adjunctive postoperative massage and vibration therapy on short-term postsurgical pain, negative affect, and physiologic stress reactivity. DESIGN: Prospective, randomized controlled trial. The treatment groups were: (1) usual postoperative care (UC); (2) UC plus massage therapy; or (3) UC plus vibration therapy. SETTING: The University of Virginia Hospital Surgical Units, Gynecology-Oncology Clinic, and General Clinical Research Center. SUBJECTS: One hundred and five (N = 105) women who underwent an abdominal laparotomy for removal of suspected cancerous lesions. INTERVENTIONS: All patients received UC with analgesic medication. Additionally, the massage group received standardized 45-minute sessions of gentle Swedish massage on the 3 consecutive evenings after surgery and the vibration group received 20-minute sessions of inaudible vibration therapy (physiotones) on the 3 consecutive evenings after surgery, as well as additional sessions as desired. OUTCOME MEASURES: Sensory pain, affective pain, anxiety, distress, analgesic use, systolic blood pressure, 24-hour urine free cortisol, number of postoperative complications, and days of hospitalization. RESULTS: On the day of surgery, massage was more effective than UC for affective (p = 0.0244) and sensory pain (p = 0.0428), and better than vibration for affective pain (p = 0.0015). On postoperative day 2, massage was more effective than UC for distress (p = 0.0085), and better than vibration for sensory pain (p = 0.0085). Vibration was also more effective than UC for sensory pain (p = 0.0090) and distress (p = .0090). However, after controlling for multiple comparisons and multiple outcomes, no significant differences were found. CONCLUSIONS: Gentle Swedish massage applied postoperatively may have minor effects on short-term sensory pain, affective pain, and distress among women undergoing an abdominal laparotomy for removal of suspected malignant tissues.     

Success and complications of four-duct ligation for sialorrhea

OBJECTIVE: Sialorrhea can have a significant negative effect on quality of life, impeding social interactions and severely limiting employment opportunities. Many surgical options to control sialorrhea have been reported. One of the newest procedures is combined ligation of the submandibular and parotid ducts, reported only once in the literature in one series of five patients to date. We have compared results in our first 21 patients undergoing this procedure with results reported in the literature for other procedures to treat sialorrhea. MATERIALS AND METHODS: We retrospectively reviewed medical records of all 21 children we treated with four-duct ligation, a relatively simple intraoral procedure to control sialorrhea, between August 1999 and September 2000 and contacted primary caregivers by telephone to answer a questionnaire regarding objective and subjective results of surgery. Surgery was considered successful when caregivers rated patients as 'much better' or 'better' after surgery. RESULTS: Follow-up was completed in all 21 of the patients 1-14 months after surgery. The success rate of four-duct ligation ('much better' or 'better' after surgery) was 81%, and no patient's sialorrhea problem was worse after surgery. Major complications occurred in two (10%) of the patients (one ranula and one case of sialoadenitis), which were both successfully treated surgically. Minor complications occurred in four (19%) of the patients, tongue swelling that prolonged hospitalization, a ranula that resolved, and prolonged submandibular gland swelling that resolved (two cases). More than half of patients were discharged the day of or the day after surgery. CONCLUSIONS: Four-duct ligation should be considered when surgery is indicated to treat sialorrhea.     

Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.