Prescription drug therapy in the podiatric outpatient population: interactions and precautions

A survey of 2,000 outpatients at the clinic of the Dr. William M. Scholl College of Podiatric Medicine was conducted analyzing both medications reported by the patients at the time of treatment and drugs by the attending podiatrist. The major groups of medications already used by the patients included diuretics, vitamins and minerals, nonsteroidal antiinflammatory drugs, cardiovascular medications, insulin and oral hypoglycemics, estrogen and thyroid hormone replacement, and antibiotics. Patients with asthma, ulcers, epilepsy, affective disorders and Parkinsonism represented significant subgroups. The major drugs used by podiatrists in the outpatient clinic included analgesics and antiinflammatory agents, local anesthetics, antibiotics, sedative-hypnotics, and a variety of topical agents. These two sources of medication serve as the basis for a review of drug interactions in the podiatric outpatient population. In addition, precautions for the use of drugs commonly administered by podiatrists are reviewed.     

The mortality rate from lung metastases in animals inhaling nitrogen dioxide (NO2)

A study was carried out to determine the interrelationship between the inhalation of nitrogen dioxide (0.4 +/- 0.50 ppm), lung metastases development from circulating cancer cells, and death rate from such metastases. C57 BL/6J mice were used in these experiments. Animals were divided into control and NO2-exposed groups, and were exposed to filtered air and 0.4 ppm of NO2, respectively. Following 12 weeks of exposure, all animals were infused intravenously with syngeneic, viable B16 melanoma cells. The results indicate that a subpopulation of NO2-exposed animals showed a significant increase in mortality rate during the early part of the experiment. The interpretation is that animals especially sensitive to the NO2 insult developed extensive metastases at an early stage. The question raised is whether or not the progression of human cancer is influenced by the inhalation of noxious pollutants in the ambient atmosphere.     

Novel anticholinesterases based on the molecular skeletons of furobenzofuran and methanobenzodioxepine

Reductive cyclization of 5-hydroxy-3-methyl-3-methoxycarbonylmethylenebenzofuran-2(3H)-one (4) gave 5-hydroxy-3a-methyl-2,3,3a,8a-tatrahydrofuro[2,3-b]benzofuran (5) and the rearrangement product 7-hydroxy-4,5-dihydro-2,5-methano-1,3-benzodioxepine (6). Reaction of compounds 5 and 6 with different isocyanates provided two series novel carbamates (7-12) whose structures were confirmed by X-ray crystallography. These were assessed for anticholinesterase action against freshly prepared human enzyme and proved to be potent inhibitors of either acetyl- (AChE) or butyrylcholinesterase (BChE) with specific compounds exhibiting remarkable selectivity. Because the two series of carbamates (7-12) differ in their phenolic moieties, their respective potency and selectivity for AChE versus BChE was governed by their N-substituted groups. This same characteristic was also present in a series of physovenine analogues (1, 13, 15, 17) and physostigmine analogues (2, 14, 16, 18). These structure-activity relations proved valuable in elucidating the mechanisms underpinning the interaction between carbamate-based cholinesterase inhibitors and their enzyme target. In addition, because physostigmine analogues have demonstrated activity in lowering the Alzheimer's disease protein, amyloid precursor protein (APP), examples of the two new series of carbamates were characterized in culture assays of quantifying cell viability and synthesis of APP.     

Integrated bioabsorbable tissue reinforcement in laparoscopic sleeve gastrectomy

Division of the stomach in laparoscopic sleeve gastrectomy may be performed using bare stapler cartridges or cartridges fitted with tissue reinforcement strips, with or without oversewing. Many tissue reinforcement strips are after-market add-on products that must be fitted onto a stapler during surgery. A retrospective review was conducted of 85 consecutive patients undergoing laparoscopic sleeve gastrectomy using a novel integrated bioabsorbable polymer buttress pre-mounted on a single-use loading unit stapler. Mean preoperative body mass index (BMI) was 41.7 ± 5.2 kg/m². Morbidity and short-term outcomes were documented. Mean follow-up was 8.1 ± 3.6 months (range, 1.0–16.2 months). There were no mortalities or staple line leaks noted in this series with short-term follow up. The major complication rate (grade III and above) was 7.1% and included: reoperation for staple line bleeding (2.4%, n = 2), gastric sleeve stenosis requiring balloon dilation (2.4%, n = 2), choledocholithiasis 2 weeks after surgery (1.2%, n = 1), and reoperation without abnormality for suspected perioperative obstruction (1.2%, n = 1). Mean percent excess BMI loss at 3 (44.6 ± 11.3), 6 (57.9 ± 17.2), and 12 months (72.4 ± 27.5) was comparable to other published series. The use of an integrated absorbable synthetic polymer for stapled tissue reinforcement in laparoscopic sleeve gastrectomy appears to be feasible and safe, and yields results consistent with other published techniques.     

Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast

Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.     

Potent cytotoxicity of an auristatin-containing antibody-drug conjugate targeting melanoma cells expressing melanotransferrin/p97

Identifying factors that determine the sensitivity or resistance of cancer cells to cytotoxicity by antibody-drug conjugates is essential in the development of such conjugates for therapy. Here the monoclonal antibody L49 is used to target melanotransferrin, a glycosylphosphatidylinositol-anchored glycoprotein first identified as p97, a cell-surface marker in melanomas. L49 was conjugated via a proteolytically cleavable valine-citrulline linker to the antimitotic drug, monomethylauristatin F (vcMMAF). Effective drug release from L49-vcMMAF likely requires cellular proteases most commonly located in endosomes and lysosomes. Melanoma cell lines with the highest surface p97 expression (80,000-280,000 sites per cell) were sensitive to L49-vcMMAF whereas most other cancer cell lines with lower p97 expression were resistant, as were normal cells with low copy numbers (< or = 20,000 sites per cell). Cell line sensitivity to L49-vcMMAF was found by immunofluorescence microscopy to correlate with intracellular fate of the conjugate. Specifically, L49-vcMMAF colocalized with the lysosomal marker CD107a within sensitive cell lines such as SK-MEL-5 and A2058. In contrast, in resistant cells expressing lower p97 levels (H3677; 72,000 sites per cell), L49-vcMMAF colocalized with caveolin-1, a protein prominent in caveolae, but not with CD107a. Thus, for antibody-drug conjugates targeting p97, antigen level and trafficking to the lysosomes are important factors for achieving robust in vitro cytotoxicity against cancer cells. Immunohistochemical analysis with L49 revealed that 62% of metastatic melanoma tumors had strong staining for p97. Overexpression of p97 in melanoma as compared with normal tissue, in conjunction with the greater sensitivity of tumor cells to L49-vcMMAF, supports further evaluation of antibody-drug conjugates for targeting p97-overexpressing tumors.     

Etirinotecan Pegol (NKTR-102) in Third-line Treatment of Patients With Metastatic or Recurrent Non–Small-cell Lung Cancer: Results of a Phase II Study

Background

Third-line treatment options are limited for patients with metastatic non–small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment.

Frequency-pulsed electron capture gas-liquid chromatography and the tryptophan color test for rapid diagnosis of tuberculous and other forms of lymphocytic meningitis.

A total of 260 samples of cerebrospinal fluid received from Egypt, the United States, Canada, and South America were examined by frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC) for tuberculous and other forms of lymphocytic meningitis. Thirty-four of the specimens were culture positive for M. tuberculosis, and four cerebrospinal fluid specimens of herpes meningitis were established by immunological techniques. The compound, 3-(2'-ketohexyl)-indoline, was found in about 60% of the Egyptian tuberculous specimens and none of the culture-positive American specimens. the carboxylic and hydroxy acid FPEC-GLC profiles were used effectively in conjunction with other clinical data to make the diagnosis even in the absence of 3-(2'-ketohexyl)indoline. Herpes meningitis and mixed infections of Myeobacterium tuberculosis-herpes, M. tuberculosis-leptospira, and M. tuberculosis-Haemophilus influenzae produced profiles different from each other and from pure culture cases. The color test for tuberculous meningitis was evaluated, and free tryptophan was eliminated as the source of color reaction. Indications are that 3-(2'-ketohexyl)indoline, in most cases, is not responsible for the positive color reaction. Differences in the clinical and FPEC-GLC data obtained from samples from different geographical regions are discussed.     

The facilitators and barriers of physical activity among Aboriginal and Torres Strait Islander regional sport participants

Background : Disparities in health perspectives between Indigenous and non‐Indigenous populations are major concerns in many of the world's well‐developed nations. Indigenous populations are largely less healthy, more prone to chronic diseases, and have an earlier overall mortality than non‐Indigenous populations. Low levels of physical activity (PA) contribute to the high levels of disease in Indigenous Australians. Method : Qualitative analysis of structured one‐on‐one interviews discussing PA in a regional setting. Participants were 12 Indigenous Australian adults, and 12 non‐Indigenous Australian adults matched on age, sex, and basketball division. Results : Most participants reported engaging in regular exercise; however, the Indigenous group reported more barriers to PA. These factors included cost, time management and environmental constraints. The physical facilitators identified by our Indigenous sample included social support, intrinsic motivation and role modelling. Conclusion : Findings describe individual and external factors that promote or constraint PA as reported by Indigenous Australian adults. Results indicate that Indigenous people face specific barriers to PA when compared to a non‐Indigenous sample. Implications for public health: This study is the first to compare the perspective of Indigenous Australians to a matched group of non‐Indigenous Australians and provides useful knowledge to develop public health programs based on culturally sensitive data.     

Clinical evaluation of aortic coarctation with 4D flow MR imaging

Purpose:

To show that 4D Flow is a clinically viable tool for evaluation of collateral blood flow and demonstration of distorted blood flow patterns in patients with treated and untreated aortic coarctation.

Materials and Methods:

Time‐resolved, 3D phase contrast magnetic resonance imaging (MRI) (4D Flow) was used to assess blood flow in the thoracic aorta of 34 individuals: 26 patients with coarctation (22 after surgery or stent placement) and eight healthy volunteers.

Results:

Direct comparison of blood flow calculated with 2D and 4D phase contrast data at standard levels for analysis in coarctation patients showed good correlation and agreement (correlation coefficient r = 0.99, limits of agreement = ?20% to 20% for collateral blood flow calculations). Abnormal blood flow patterns were demonstrated at peak systole with 4D Flow visualization techniques in the descending thoracic aorta of patients but not volunteers. Marked helical flow was seen in 9 of 13 patients with angulated aortic arch geometries after coarctation repair. Vortical flow was seen in regions of poststenotic dilation.

Conclusion:

4D Flow is a fast and reliable means of evaluating collateral blood flow in patients with aortic coarctation in order to establish hemodynamic significance. It also can detect distorted blood flow patterns in the descending aorta after coarctation repair. J. Magn. Reson. Imaging 2010;31:711–718. © 2010 Wiley‐Liss, Inc.