Permanent diversion rates after neoadjuvant therapy and coloanal anastomosis for rectal cancer.

BACKGROUND: The aim of this study was to assess the rate of permanent diversion in patients undergoing coloanal anastomosis after neoadjuvant therapy for rectal cancer. METHODS: We performed a retrospective review of patients with rectal cancer who underwent a total mesorectal excision of a tumor within 9 cm of the anal verge. RESULTS: There were 201 patients who underwent resection with coloanal anastomosis, with a mean follow-up period of 51 months. The average tumor distance from the anal verge was 7 cm (range, 4-9 cm). Neoadjuvant therapy was administrated in 145 patients, 47 had no radiation, and 9 received radiation postoperatively. Thirty-two patients (16%) had long-term complications including incontinence, fistulas, and strictures. Twenty-five patients (12%) had recurrent disease, 16 of these were local recurrence. The total rate of permanent diversion was 29 (14%). Reasons for diversion included local recurrence in 12 patients (6%), complications in 10 patients (5%), and poor function in 7 patients (3%). CONCLUSIONS: Poor bowel function, late complications, and local recurrence all contribute to permanent diversion after a coloanal anastomosis. Neoadjuvant therapy in conjunction with a total mesorectal excision and coloanal anastomosis leads to acceptably low permanent diversion rates in the vast majority of patients.

Clinical outcomes of complicated diverticulitis managed nonoperatively.

BACKGROUND: Surgical resection is typically recommended for patients with computed tomography (CT)-confirmed complicated diverticulitis. This study was designed to assess outcomes of patients with complicated diverticulitis managed nonoperatively. METHODS: A retrospective study covering 14 years evaluated patients with complicated diverticulitis diagnosed by CT scan. Patient outcomes, including recurrence and need for operations, were reviewed. RESULTS: Of 256 patients identified, 99 were managed nonoperatively. Forty-six of the 99 patients had a recurrent episode of diverticulitis. Of these 46 patients, 20 underwent a sigmoid colon resection, with only 1 patient requiring a colostomy for obstruction. None of these recurrences resulted in the need for emergency resection. CONCLUSIONS: Surgical treatment should play an important role in the management of patients with complicated diverticulitis because of the high risk of recurrence. However, nonoperative management may be appropriate in a select population if age or medical comorbidities preclude a safe operation since the need for emergency operation is unlikely.

Risk of late bleeding following hemorrhoidal banding in patients on antithrombotic prophylaxis.

BACKGROUND: The risk of bleeding following rubber band ligation of internal hemorrhoids is 1%-2%. This risk may be increased in patients taking antithrombotic therapy. The goal of the current study was to find a safer approach to banding without increasing the risk of bleeding. METHODS: This retrospective review identified patients undergoing banding while on antithrombotic therapy. These medications were held for 7-10 days following the procedure. The number of bands placed while on antithrombotic therapy and their post band complications were recorded. RESULTS: There were 605 bands placed on 364 patients taking antithrombotic medications. There were 23 complications involving bleeding, a value that was not statistically different from those not taking antithrombotic therapy. Patients on clopidogrel experienced 50% of the significant bleeding episodes and 18% of the insignificant bleeding episodes. CONCLUSIONS: Holding antithrombotic medication following banding appears to equalize the risk of bleeding to that of patients not taking antithrombotic medications. Patients taking clopidogrel may be at higher risk for bleeding complications.

Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex.

PURPOSE: To evaluate the effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the cytochrome oxidase blobs of V1 cortex in the macaque visual system. METHODS: Monocular experimental glaucoma was induced in adult monkeys (Macaca mulatta and Macaca fascicularis) by laser application to the trabecular meshwork, increasing the intraocular pressure. After other experiments, the primary visual cortices were analyzed for functional excitation from surviving ganglion cells, as indicated by cytochrome oxidase histochemistry. RESULTS: Cytochrome oxidase reactivity was uniformly reduced in blobs with input from the glaucomatous eye in a manner consistent with loss of known afferent inputs. The average size of glaucomatous blobs in layers 2 and 3 of V1 cortex was reduced by half. CONCLUSIONS: Experimental glaucoma in monkeys reduces retinal input to the central nervous system, thereby reducing the metabolic drive to downstream targets, as indicated by the reduction in the size of cytochrome oxidase blobs in layers 2 and 3 of V1 cortex. The pattern of cytochrome oxidase loss within the blob was uniform, suggesting that all sources of afferent input to the blobs were affected by experimental glaucoma.

Analysis of expressed sequence tags indicates 35,000 human genes.

The number of protein-coding genes in an organism provides a useful first measure of its molecular complexity. Single-celled prokaryotes and eukaryotes typically have a few thousand genes; for example, Escherichia coli has 4,300 and Saccharomyces cerevisiae has 6,000. Evolution of multicellularity appears to have been accompanied by a several-fold increase in gene number, the invertebrates Caenorhabditis elegans and Drosophila melanogaster having 19,000 and 13,600 genes, respectively. Here we estimate the number of human genes by comparing a set of human expressed sequence tag (EST) contigs with human chromosome 22 and with a non-redundant set of mRNA sequences. The two comparisons give mutually consistent estimates of approximately 35,000 genes, substantially lower than most previous estimates. Evolution of the increased physiological complexity of vertebrates may therefore have depended more on the combinatorial diversification of regulatory networks or alternative splicing than on a substantial increase in gene number.

Solid-phase combinatorial synthesis using MicroKan reactors, Rf tagging, and directed sorting.

A modular system for high-output solid-phase combinatorial synthesis has been designed and developed. The system employs three technological innovations to achieve its high efficiency and reliability: (1) application of microreactors as the reaction units in solid-phase synthesis; (2) use of radiofrequency tagging as the non-chemical tracking method; and (3) development of the directed sorting technology for split & pool synthesis. The system has been successfully applied in the synthesis of compound libraries of several hundred to several thousand compounds in multi-milligrams per compound quantity by many organizations.

High school athletes and marijuana use.

Identifying groups of young people that might be especially susceptible to marijuana use would aid in the design and implementation of drug policy programs. This article examines whether those who participated in high school athletics have a different pattern of marijuana use than comparable non-athletes. The results indicate that male athletes have a higher incidence of marijuana use than non-athletes. The same is not true for female athletes, who actually engage in less marijuana use than their non-athlete counterparts. However, female athletes are more likely than non-athletes to wait until their post-high school years to try the drug for the first time.

Base-calling of automated sequencer traces using phred. I. Accuracy assessment.

The availability of massive amounts of DNA sequence information has begun to revolutionize the practice of biology. As a result, current large-scale sequencing output, while impressive, is not adequate to keep pace with growing demand and, in particular, is far short of what will be required to obtain the 3-billion-base human genome sequence by the target date of 2005. To reach this goal, improved automation will be essential, and it is particularly important that human involvement in sequence data processing be significantly reduced or eliminated. Progress in this respect will require both improved accuracy of the data processing software and reliable accuracy measures to reduce the need for human involvement in error correction and make human review more efficient. Here, we describe one step toward that goal: a base-calling program for automated sequencer traces, phred, with improved accuracy. phred appears to be the first base-calling program to achieve a lower error rate than the ABI software, averaging 40%-50% fewer errors in the data sets examined independent of position in read, machine running conditions, or sequencing chemistry.

Base-calling of automated sequencer traces using phred. II. Error probabilities.

Elimination of the data processing bottleneck in high-throughput sequencing will require both improved accuracy of data processing software and reliable measures of that accuracy. We have developed and implemented in our base-calling program phred the ability to estimate a probability of error for each base-call, as a function of certain parameters computed from the trace data. These error probabilities are shown here to be valid (correspond to actual error rates) and to have high power to discriminate correct base-calls from incorrect ones, for read data collected under several different chemistries and electrophoretic conditions. They play a critical role in our assembly program phrap and our finishing program consed.

Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase.

Previously we had shown that tripeptidyl trifluoromethyl ketones (TFMKs) possessing an N-terminal diarylacylsulfonamide, such as ICI 200,880 and ICI 200,355, displayed unparalleled protection against the lung damage induced by human neutrophil elastase (HNE) when the inhibitors were administered intratracheally. Since the diarylacylsulfonamides were designed specifically to afford a long residence time in the lung, it was not unexpected that inhibitors from this class of TFMKs were not active when administered orally. Upon evaluating a large number of peptidyl TFMKs possessing a variety of N-terminal groups, several compounds were identified which demonstrated oral activity. Compounds were evaluated for their oral activity by measuring their ability to inhibit the increase in lung weight relative to body weight (Lw/Bw), the increase in red blood cells, and the increase in white blood cells induced by intratracheally administered HNE (100 micrograms/hamster). A number of tripeptidyl trifluoromethyl ketones containing neutral N-terminal groups displayed good oral activity, while those containing basic, acidic, or polar groups did not. Compound 50, possessing an N-terminal 4-(CH3O)C6H4CO group, was particularly effective, reducing Lw/Bw by 77%, red cells by 89%, and white cells by 91% when dosed at 37.5 mg/kg orally. Thus, by modifying the N-terminal group of tripeptidyl TFMKs, inhibitors can be designed which are effective in vivo when administered either orally or intratracheally.

Population and economic growth: a cointegration analysis of lesser developed countries.

PIP: The authors examine the temporal relationship between population growth and economic growth in Nepal, India, Ghana, Sri Lanka, Bolivia, Philippines, Guatemala, Syria, Peru, Thailand, Chile, Argentina, and Mexico, conducting Granger-causality tests in the context of error correction models when cointegration is present. Their goal is to provide additional time series econometric evidence on the short-run and long-run time series behavior of population growth and the growth of real per capita gross domestic product for a sample of low to middle income developing countries. Cointegration was found in only 3 of the 13 countries examined. Even though 10 countries in this study exhibited no properties of cointegration, researchers conducting time series studies of the relationship between population growth and economic growth using differenced data should nonetheless evaluate the possible long-term relationship. Capturing the short- and long-run behaviors of the respective time series may give the researcher a more robust test of Granger-causality.^ieng

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.

Management of illness and temporary disability in children enrolled in day-care centers. The Health House experience.

Alternative care arrangements are often necessary when children enrolled in day-care centers experience illness or temporary disability. To meet this need, a new facility named Health House was established by the Child Development Program of the Pomona (Calif) Unified School District. This report describes the organization, operation, and costs of the program, and reviews the management of 179 episodes of illness or temporary disability in 99 children served by the program during the 1983-1984 school year. The medical conditions of patients cared for were comparable with those seen in physicians' offices as reported in a national survey. The daily cost of care per child for the sponsoring agency was $38. The service enabled an average daily salary saving of $39.80 for the working parent. Health House may serve as a model for the management of illness or temporary disability in children enrolled in day-care centers.

Physical working capacity and mile run performance in adolescent boys.

The degree of generality between the endurance characteristics of the one mile run and PWC170 tests was examined with a group of fifteen year old boys who performed both tests once a week for three weeks. A significant improvement in performance of both tests was found between trials 1 and 2, which was sustained between trials 2 and 3. These results suggest that norm scales regarding performance in both tests should be based on the average of at least two trials following a practice trial. The results of the present study also suggest that when average scores are used, rather than single scores, the amount of generality between the endurance characteristics of the one mile run and PWC170 test is high enough to allow physical working capacity to be predicted fairly accurately from performance in the one mile run.

Evaluation of the Swank IL-201 transfusion filter.

The effects of a new transfusion filter (Swank IL-20U) on stored, whole blood have been examined. Six filters were preloaded by passage of two units of outdated, type-specific bank blood, and the effects of filtration on a third unit of 21-day-old blood flowing under 150 mm Hg pressure were measured. Filtration did not significantly alter erythrocyte or leukocyte count, total or plasma hemoglobin, red-cell fragility, and plasma sodium, potassium, albumin, or globulin. Platelet counts were reduced by 33%. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen protein, wet and dry weight of material retained, and scanning electron microscopy, was shown to be effective over the entire range of particle size. In comparison with other transfusion filters previously examined in this laboratory, the Swank IL-201 filter combines the features of efficient microaggregate removal with moderate blood-flow rate. Compared to its predecessor, the Swank IL-200, this new filter design has improved flow characteristics without loss of microaggregate removal efficiency. In view of the similarity of performance demonstrated for several of the available filters, it seems likely that relative cost will constitute an important determinant of filter selection.

An evaluation of the Bentley PFF-100 transfusion filter.

The effects of a new transfusion filter (Bentley PFF-100) on stored whole blood have been examined. Six filters were preloaded by passage of two units of outdated type-specific bank blood and the effects of filtration on a third unit of 21-day-old blood flowing under 19.95 kPa (150 mm Hg) pressure were measured. Filtration did not significantly alter erythrocyte or leukocyte count, total or plasma haemoglobin, red cell fragility, plasma sodium, potassium, albumin, or globulin. Platelet counts were reduced by 31%. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen protein, wet and dry weight of material retained and scanning electron microscopy, was shown to be effective over the entire range of particle size. In comparison with other transfusion filters previously examined in this laboratory, the Bentley PFF-100 filter combines the feature of moderately efficient microaggregate removal with rapid blood flow rate. Compared to its predecessor, the Bentley PF-127, this new filter design has improved flow characteristics without loss of efficiency of microaggregate removal.

Effects of Fenwal 4C2423 transfusion microfilter on microaggregates and other constituents of stored blood.

The effects of a new micropore transfusion filter (Fenwal 4C2423) on stored whole blood have been examined. Five filters were preloaded by passage of two units of outdated type specific bank blood, and the effects of filtration on a third unit, consisting of 21-day-old blood, flowing under 150 mmHg pressure, were measured. Filtration did not significantly alter red blood cell count, total hemoglobin, red blood cell fragility, plasma sodium, potassium, albumin, or globulin. Some platelets and white blood cells were removed and a small amount of hemolygis of erythrocytes (less than 0.1%) was observed. Removal of microaggregates, assessed by Coulter counting, screen filtration pressure, total screen porteins, wet and dry weights of material retained, and scanning electron microscopy, was shown to be excellent over the entire range of particle size. Comparison of the Bentley PFS-127, Fenwal 4C2417, Johnson & Johnson Intersept, Pall Ultipore, and Swank IL200 filters led to the conclusion that the Fenwal 4C2423 was both a significant improvement over the previous Fenwal design and comparable to the most efficient of these filters for both the removal of microaggregates during massive blood transfusion and for the blood flow rates obtained.

Western pine beetle: specificity among enantiomers of male and female components of an attractant pheromone.

The flight response of both sexes of Dendroctonus brevicomis to the mixture of myrcene, racemic frontalin, and (1R,5S,7R)-(+)-exo-brevicomin and to the mixture of myrcene, (1S,5R)-(-)-frontalin and racemic exo-brevicomin was significantly greater than the response to the same mixtures in which the antipodes were substituted. The flight response to these two mixtures was also greater than the response to the ternary mixture of myrcene, racemic frontalin, and racemic exo-brevicomin (MFE). The walking response of both sexes to the mixture of myrcene, racemic frontalin, and (+)-exo-brevicomin was not different from the response to MFE. Substitution of the antipode lowered the response when compared to that of MFE. When evaporated with ponderosa pine turpentine, (-)-frontalin was active in the field while its antipode was not.