Organ preservation in anal and rectal cancers

For the past 10 to 15 years, radiation therapy and chemotherapy have played an increasingly important role in the treatment of various gastrointestinal malignancies, most prominently in anal and rectal cancer. Critical issues in the care of patients with anal and rectal cancer include not only local control and survival but organ preservation as well. For patients with carcinoma of the anal canal, external-beam irradiation with 5-fluorouracil and chemotherapy with mitomycin C have replaced surgery as primary therapy. Current studies are optimizing this therapy. In contrast, the management of distal rectal cancer is in evolution. Although the abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with substantial morbidity (loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction). As an alternative, treatment programs utilizing sphincter-preserving procedures with radiation therapy and chemotherapy are under active investigation. In selected patients, these strategies appear promising, and there have been reports of satisfactory local control and survival, as well as preservation of sphincter integrity.     

A predictive model for matrix and analyte effects in electrospray ionization of singly-charged ionic analytes

In electrospray ionization (ESI), droplets with a surface excess charge are created. The rate of production of surface excess charge is a constant and is equal to the rate of ion production. The ions appearing in the mass spectrum are postulated to be those that formed the surface excess charge at the time of droplet formation (or their collision products). An equilibrium model based on competition among the ions in the solution for the limited number of excess charge sites has been developed. This model accurately predicts the response curves of singly-charged ionic analytes as a function of the concentration of electrolyte and other analytes and provides an explanation for the selective effectiveness of ESI. At low concentrations of total analyte (micromolar and less), the response curves are linear, indifferent to the presence of other low concentration analytes, and suppressed by electrolyte concentrations in excess of the minimum required. At higher analyte concentrations, the response becomes independent of analyte concentration but highly affected by the presence of other analytes.     

Response of Plasmodium falciparum to chloroquine and Fansidar in vivo and chloroquine and amodiaquine in vitro in Uganda

The response of P. falciparum to chloroquine and pyrimethamine-sulfadoxine in vivo and chloroquine and amodiaquine in vitro was investigated in parasitaemic school children from six locations. Mean parasite sensitivity to chloroquine at day 7 was 74% (range 61-97) with parasite clearance rates between 2-3 days and complete defervescence in 85% of febrile children. Sensitivity declined in the four sites followed up to day 14 to 45% (range 37-53). Parasites were significantly more sensitive to pyrimethamine/sulfadoxine at 5/6 sites (100% day 7) but 5% of subjects became parasitaemic by day 14. In vitro isolates were significantly less sensitive to chloroquine than to amodiaquine with a mean 99% effective concentration of 348 mumol/L compared to 6.44 mumol/L. Clearly the role of chloroquine as the primary therapy for uncomplicated P. falciparum malaria should be reconsidered especially in the light of increasing disease severity and resurgence. Amodiaquine may be suitable alternative with pyrimethamine/sulfadoxine as second line and for more severe malaria prior to referral. The cost of alternative antimalarials and the dynamic and deteriorating pattern of resistance are powerful arguments for more objective slide diagnosis to minimise drug pressure and a regular drug sensitivity surveillance system. We believe that the latter should concentrate on measuring clinical drug efficacy in symptomatic outpatients rather than in asymptomatic children while the former needs more pragmatic and economical strategies possibly centred on seasonality and risk.     

Early American neurologic textbooks

Although European treatises were translated and available to American doctors interested in neurology during the 19th century, the early American neurologic textbooks were distinctive in their comprehensive integration of basic and clinical science. William A. Hammond, in 1871, published the first comprehensive American textbook of neurology, preceding the manuals by Gowers (1886) and Oppenheim (1894) by more than a decade. Four other American adult neurologic textbooks expanded on Hammond's model and incorporated other important topics, including neurologic anatomy, the formal examination, neurochemistry, and complete bibliographies. Bernard Sachs' 1895 textbook was the first pediatric neurologic textbook published in America and made significant contributions to the organization of childhood neurologic disorders. These works functioned as centralized resources for neurologic information, were influential educational tools, and helped foster a growing appreciation of the American neurologic school both nationally and internationally.     

9-Benzyladenines: potent and selective cAMP phosphodiesterase inhibitors

A 6-year-old Quarter Horse gelding with acute onset of a grade-4/5 lameness of the left forelimb 21 days after an encounter with a porcupine was examined. Quills had been removed by the referring veterinarian, and the horse had been treated with antibiotics and hydrotherapy for 14 days. The horse was pyretic and had effusion in the digital synovial sheath. Signs of pain were elicited on palpation of the area. A tentative diagnosis of septic tenosynovitis caused by a porcupine quill was made. Exploratory tenoscopy revealed large amounts of fibrin in the sheath and a 1.2-cm quill. Bacteriologic culture of synovial fluid yielded a pure growth of Staphylococcus aureus. The horse improved dramatically after tenoscopic removal of the quill, debridement of fibrin, and lavage to dilute inflammatory mediators and bacteria, debridement of fibrin, discovery and removal of a quill, and complete evaluation of the sheath for prognostic purposes. Tenoscopy can provide a means for direct observation and enhance the ability of clinicians to debride a septic synovial sheath in a minimally invasive manner.     

Detection of West Nile virus by the polymerase chain reaction and analysis of nucleotide sequence variation

A polymerase chain reaction (PCR) assay was developed to rapidly detect and identify West Nile (WN) virus. The RNA from seven isolates of WN virus from six countries and four other flaviviruses (Kunjin, Japanese encephalitis, St. Louis encephalitis, and yellow fever viruses) was reverse-transcribed (RT) and amplified by PCR. The nucleotide sequences of the amplified products were determined by a rapid, automated DNA sequencing method. The WN virus RT/PCR assay detected the target gene segment of sequencing method. The WN virus RT/PCR assay detected the target gene segment of isolates from both the African-Middle Eastern group and the Indian group with a sensitivity of approximately 0.05 pg of viral RNA. Kunjin virus was the only other flavivirus tested that produced a band of the appropriate size. Five of seven WN virus isolates showed 92-98% homology in the nucleotide sequence of their PCR products. The sequence of one isolate was virtually identical to the published sequence of the Nigerian isolate (99.5% homology). No correlation was established between the degree of nucleotide homology, geographic location, time of isolation, or source of the isolates.     

Characterization of the membrane-associating domain of the sperm adhesive protein, bindin

Male Swiss-Webster mice were rendered tolerant to morphine by subcutaneous implantation of a morphine pellet, each containing 75 mg morphine base, for 3 days. Mice implanted with placebo pellets served as controls. A high degree of tolerance to the analgesic effect of morphine developed as evidenced by decreased analgesic response to various doses of morphine. A selective kappa-opiate agonist, U-50,488H (8, 16 and 32 mg/kg, i.p.) produced dose-dependent analgesic and hypothermic effects in mice implanted with placebo pellets. A significant decrease in the analgesic and hypothermic effects of U-50,488H was observed in morphine tolerant mice as compared to placebo-treated mice. Mice were rendered tolerant to U-50,488H by injecting the drug (25 mg/kg, i.p.) twice daily for 4 days. Vehicle injected mice served as controls. Tolerance to the analgesic and hypothermic effects of U-50,488H in mice injected chronically with the drug was evidenced by the decreases in the intensity of these responses when compared to those observed in vehicle injected controls. Morphine produced a dose-dependent analgesic and hypothermic effects in mice injected chronically with vehicle but the intensity of these effects was significantly lower in mice injected chronically with U-50,488H. These results indicate that a substantial tolerance to analgesic and hypothermic effects of U-50,488H develops in morphine tolerant mice. The effect of chronic injections of U-50,488H on the binding of [3H]ethylketocyclazocine (EKC) and [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin (DAMGO) to whole brain and spinal cord kappa- and mu-opiate receptors was determined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Femoral artery pseudoaneurysms: risk factors, prevalence, and treatment options

Femoral artery pseudoaneurysms (PSA or false aneurysm) develop in about 1% of patients undergoing procedures that require femoral artery cannulation. PSA prolong hospitalization, consuming health-care resources, and result in significant morbidity. We designed a study to review the prevalence, risk factors, and treatment of PSA. We performed a retrospective, case-controlled study of patients diagnosed with PSA at a large, urban, tertiary-care teaching hospital. We reviewed 48 patients with PSA for our study. The estimated prevalence of PSA was 0.28%, with identical rates found for procedures done in the interventional radiology department and in the cardiac catheterization suite. Logistic regression identified three independent risk factors for developing PSA: being female (odds ratio 2.62), having an intervention performed (odds ratio 3.22), and not having a closure device used (odds ratio 10.2). Patients with PSA had longer hospital length of stay than that of patients without PSA. We found no statistically significant difference in failure or complication rates for the four treatment options and that spontaneous resolution of PSA does not correlate with its size. Thrombin injection and observation are effective, low-complication treatment options.