A phase II trial of weekly infusional 5-fluorouracil in combination with low-dose leucovorin in patients with advanced colorectal cancer

We examined 59 breast cancers for p53 and bcl-2 protein expression by immunohistochemistry. The results were correlated with Ki-67 immunostaining. p53-negativity was noted in 40 cases and the remaining 19 tumours were p53-positive. Thirty-six tumours showed strong expression of bcl-2 and in 23 no staining for this protein was observed. We found statistically significant reverse correlation between expression of p53 and bcl-2 in majority of carcinomas: 31 cases were bcl-2 positive and p53-negative, and 14 tumours were bcl-2-negative and p53-positive. Six carcinomas showed no nuclear staining for Ki-67 and in the remaining 53 the percent of cancer cells positive for Ki-67 ranged from 1 to 60 (mean: 14.6). In these 53 cases we found that bcl-2-positive tumours were characterized by lower proliferation than bcl-2-negative tumours, the mean value of Ki-67 immunostaining being 10.7% and 23.0%, respectively. p53-negative tumours showed lower proliferation than p53-positive tumours: mean Ki-67 index was 10.2% and 23.9%, respectively. We conclude that immunohistochemically detected p53 and bcl-2 proteins show a significant inverse relationship in majority of breast carcinomas and their expression correlates with tumour proliferation (Ki-67 immunostaining).     

Fetal survival in abdominal pregnancy: a review of 11 cases

PURPOSE: Little has been written regarding the ultrasound imaging features that might allow prediction of fetal viability in abdominal pregnancies. Toward this goal, we present our experience with a series of 11 abdominal pregnancies. MATERIALS AND METHODS: From 1981 to 1993, 11 patients presented to Universidad Catolica, Santiago, and Universidad de Austral, Valdivia, Chile, with third trimester abdominal pregnancies. Five had complete ultrasound examinations, and these five patients were managed expectantly. The other six women presented as acute abdominal emergencies and underwent emergent surgery. RESULTS: Four of five fetuses that survived had a complete placental attachment to the uterus, and one surviving neonate had a partial attachment of the placenta to the uterus. Three fetuses died prior to delivery, and all three had a complete mesenteric placental attachment. Two died in the early neonatal period. One had a complete uterine placental attachment, and the other had a partial attachment. CONCLUSIONS: The survival rate of abdominal pregnancies may be better than is generally believed. Placental attachment to the uterus appears to be a factor related to fetal survival and maternal morbidity. More cases are necessary to determine the feasibility of managing women with abdominal pregnancies expectantly.     

Identification and molecular characterization of two tandemly located flagellin genes from Aeromonas salmonicida A449

Two tandemly located flagellin genes, flaA and flaB, with 79% nucleotide sequence identity were identified in Aeromonas salmonicida A449. The fla genes are conserved in typical and atypical strains of A. salmonicida, and they display significant divergence at the nucleotide level from the fla genes of the motile species Aeromonas hydrophila and Aeromonas veronii biotype sobria. flaA and flaB encode unprocessed flagellins with predicted Mrs of 32,351 and 32,056, respectively. When cloned under the control of the Ptac promoter, flaB was highly expressed when induced in Escherichia coli DH5alpha, and the FlaB protein was detectable even in the uninduced state. In flaA clones containing intact upstream sequence, FlaA was barely detectable when uninduced and poorly expressed on induction. The A. salmonicida flagellins are antigenically cross-reactive with the A. hydrophila TF7 flagellin(s) and evolutionarily closely related to the flagellins of Pseudomonas aeruginosa and Vibrio anguillarum. Electron microscopy showed that A. salmonicida A449 expresses unsheathed polar flagella at an extremely low frequency under normal laboratory growth conditions, suggesting the presence of a full complement of genes whose products are required to make flagella; e.g., immediately downstream of flaA and flaB are open reading frames encoding FlaG and FlaH homologs.     

Underrecognition of cervical Neisseria gonorrhoeae and Chlamydia trachomatis infections in the emergency department

OBJECTIVES: 1) To quantify the frequency of underrecognized Neisseria gonorrhoeae and Chlamydia trachomatis cervical infections in women tested in the ED, 2) to describe and compare the characteristics of those treated and not treated during the initial visit, and 3) to quantify the delay interval until treatment was provided. METHODS: A 2-year, retrospective consecutive case series was performed from June 1, 1992, to May 31, 1994. There were 148 women with > or = 1 discrete occurrence of culture-proven cervical N. gonorrhoeae or C. trachomatis infection studied. All the patients were evaluated in a university-affiliated, tertiary care hospital-based ED with a large rural referral area. The main outcome measures were the proportions of patients with positive cultures both treated and not treated in the ED, the clinical characteristics of each group, and the proportion remaining untreated or experiencing treatment delays of > 2 weeks after attempted phone, mail, and public health follow-up. RESULTS: Of 157 occurrences of positive cultures for N. gonorrhoeae or C. trachomatis, 86 (53%) were treated with a regimen suggested by the CDC prior to ED release. The proportion of women with isolated C. trachomatis infections that were underrecognized and untreated initially was larger than the proportions with isolated N. gonorrhoeae or combined infections (79% vs 27% and 53%, respectively, p < 0.0001). Women with findings suggestive of advanced disease (history of fever or chills, or examination evidence of temperature > 38 degrees C, purulent vaginal discharge, or any uterine/salpinx/ovarian tenderness) were more often recognized and treated with appropriate antibiotics initially (p = 0.02 to < 0.00001 for all). After phone, mail, and public health follow-up, treatment could not be documented for 25% of the occurrences, in all cases due to an inability to locate the patient. An additional 20% of the women did not receive treatment for 14-60 days. CONCLUSIONS: In this population, both N. gonorrhoeae and C. trachomatis cervical infections are frequently underrecognized in the ED, with isolated C. trachomatis infections associated with significantly higher proportions of underrecognition. Many affected women remain untreated for extended intervals, creating public and individual health risks. Improved point of contact detection, follow-up, and treatment policies are needed to limit these risks.     

Relative sedimentation of hematopoietic progenitors in human cord blood, peripheral blood, and bone marrow as determined by counterflow centrifugal elutriation

OBJECTIVE: Although there have been many studies of the outcome of anorexia nervosa, methodological weaknesses limit their interpretation. The authors used a case-control design to try to improve knowledge about the outcome of anorexia nervosa. METHOD: All new female patients referred to an eating disorders service between Jan. 1, 1981, and Dec. 31, 1984, who had probable or definite anorexia nervosa were eligible for inclusion. Of these women, 86.4% (N = 70) were located and agreed to participate. The comparison group (N = 98) was a random community sample. All subjects were interviewed with a structured diagnostic instrument. RESULTS: A minority of the patients (10%) continued to meet the criteria for anorexia nervosa a mean of 12 years after initial referral. Even among those who no longer met these criteria, relatively low body weight and cognitive features characteristic of anorexia nervosa (perfectionism and cognitive restraint) persisted. The rates of lifetime comorbid major depression, alcohol dependence, and a number of anxiety disorders were very high. CONCLUSIONS: In the managed care/brief treatment era, therapeutic approaches with an excessive focus on weight gain that neglect the detection and treatment of associated psychological features and comorbidity may be inappropriate. Anorexia nervosa is a serious psychiatric disorder with substantial morbidity.     

Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron-withdrawing groups in place of methyl

In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble.     

Adverse environmental conditions in the respiratory and medical ICU settings

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.     

Alfalfa yield response to inoculation with recombinant strains of Rhizobium meliloti with an extra copy of dctABD and/or modified nifA expression

The construction of rhizobial strains which increase plant biomass under controlled conditions has been previously reported. However, there is no evidence that these newly constructed strains increase legume yield under agricultural conditions. This work tested the hypothesis that carefully manipulating expression of additional copies of nifA and dctABD in strains of Rhizobium meliloti would increase alfalfa yield in the field. The rationale for this hypothesis is based on the positive regulatory role that nifA plays in the expression of the nif regulon and the fact that a supply of dicarboxylic acids from the plant is required as a carbon and energy source for nitrogen fixation by the Rhizobium bacteroids in the nodule. These recombinant strains, as well as the wild-type strains from which they were derived, are ideal tools to examine the effects of modifying or increasing the expression of these genes on alfalfa biomass. The experimental design comprised seven recombinant strains, two wild-type strains, and an uninoculated control. Each treatment was replicated eight times and was conducted at four field sites in Wisconsin. Recombinant strain RMBPC-2, which has an additional copy of both nifA and dctABD, increased alfalfa biomass by 12.9% compared with the yield with the wild-type strain RMBPC and 17.9% over that in the uninoculated control plot at the site where soil nitrogen and organic matter content was lowest. These increases were statistically significant at the 5% confidence interval for each of the three harvests made during the growing season. Strain RMBPC-2 did increase alfalfa biomass at the Hancock site; however, no other significant increases or decreases in alfalfa biomass were observed with the seven other recombinant strains at that site. At three sites where this experiment was conducted, either native rhizobial populations or soil nitrogen concentrations were high. At these sites, none of the recombinant strains affected yield. We conclude that RMBPC -2 can increase alfalfa yields under field conditions of nitrogen limitation, low endogenous rhizobial competitors, and sufficient moisture.