Influence of palliative surgical resection on overall survival in patients with advanced colorectal cancer: a retrospective single institutional study.

BACKGROUND: The role of palliative surgical resection in patients presenting with locally advanced or metastatic colorectal cancer (CRC) is unclear. Resection is often limited to symptomatic management of bleeding, obstruction, perforation or for relief of pain, in patients with an adequate performance status and an expected life span of over several weeks. An exploratory analysis to evaluate the influence of a palliative surgical resection on survival outcome in patients with advanced CRC is reported. METHOD: A retrospective review of medical records of all patients diagnosed with advanced CRC at our institution between the years 1998 and 2003 was undertaken. Tumour registry data were reviewed to identify age, gender, modalities of therapy [i.e. surgery (S), chemotherapy (C), radiation] and overall survival. IRB approval was obtained for this study. RESULTS: One hundred and eighty-five patients were identified. Median age was 67 years (range 30-99). M:F ratio was 1:1. Sixty-two per cent of patients (115/185) underwent a palliative surgical intervention. Median survival of patients who underwent S and those that did not undergo S was 22 and 3 months respectively (P < 0.0001). Forty-eight per cent of patients (79/184) underwent systemic C. Median survival of patients who received C + S, and patients who received C alone was 30 and 15 months respectively (P < 0.0004). Fifty-one per cent of patients who underwent S, received C; 30% of patients who did not undergo S, received C. Chemotherapy data were available on 46 of 79 patients. Patients treated with S + C, and C without S, received a median of 9 and 6 months of therapy respectively. The median number of regimens used were similar in both. CONCLUSION: These exploratory data suggest a positive influence of a palliative resection performed during the disease course of patients with advanced CRC. The increased frequency of utilization and the more prolonged duration of C in the surgically treated patients may in part contribute to this improved survival. This may also be reflective of performance status at the time of diagnosis. Future trials enrolling patients with advanced CRC should prospectively stratify for surgical intervention to further clarify the influence of this modality on the outcome of systemic therapy in this disease.

Relationship between Endopolyploidy and Cell Size in Epidermal Tissue of Arabidopsis.

Relative quantities of DNA in individual nuclei of stem and leaf epidermal cells of Arabidopsis were measured microspectrofluorometrically using epidermal peels. The relative ploidy level in each nucleus was assessed by comparison to root tip mitotic nuclei. A clear pattern of regular endopolyploidy is evident in epidermal cells. Guard cell nuclei contain levels of DNA comparable to dividing root cells, the 2C level (i.e., one unreplicated copy of the nuclear DNA). Leaf trichome nuclei had elevated ploidy levels of 4C, 8C, 16C, 32C, and 64C, and their cytology suggested that the polyploidy represents a form of polyteny. The nuclei of epidermal pavement cells were 2C, 4C, and 8C in stem epidermis, and 2C, 4C, 8C, and 16C in leaf epidermis. Morphometry of epidermal pavement cells revealed a direct proportionality between nuclear DNA level and cell size. A consideration of the development process suggests that the cells of highest ploidy level are developmentally oldest; consequently, the developmental pattern of epidermal tissues can be read from the ploidy pattern of the cells. This observation is relevant to theories of stomate spacing and offers opportunities for genetic analysis of the endopolyploidy/polyteny phenomenon.

Rosai Dorfman disease--a clinico-pathological presentation.

Rosai Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder that typically manifests as lymphadenopathy and systemic symptoms. The authors report a 45 year old lady who presented with nasal mass and generalised lymphadenopathy. Histopathological examination demonstrated lymphophagocytosis (emperipolesis) consistent with a diagnosis of RDD. The clinical and histologic aspects of the disease are discussed as a rare cause of generalised lymphadenopathy.

Ethanol-induced neutrophil apoptosis is mediated through nitric oxide.

Clinical reports indicate that acute ethanol intoxication in chronic ethanol abusers is associated with neutropenia. We hypothesize that ethanol accelerates the apoptosis of neutrophils thus decreasing the peripheral blood count of neutrophils. We studied the effect of ethanol on neutrophil apoptosis in vivo as well as in vitro. Human neutrophils harvested from healthy subjects after an alcohol drinking binge showed enhanced apoptosis (before, 0.5+/-0.25 vs. after, 26.1+/-2.6% apoptotic neutrophils/field). Peritoneal neutrophils isolated from ethanol-treated rats also showed increased (P < 0.0001) apoptosis when compared with neutrophils isolated from control rats (control, 0.8+/-0.2% vs. ethanol, 11.8+/-0.7% apoptotic neutrophils/field). In in vitro studies, ethanol in concentrations of 50 mM and higher accelerated the apoptosis of human and rat neutrophils. This effect of ethanol on human neutrophils was time dependent. DNA isolated from ethanol-treated human neutrophils displayed integer multiples of 180 base pairs (ladder pattern), further confirming the effect of ethanol on neutrophil apoptosis. N(G)-monomethyl-L-arginine monoacetate and N(G)-nitro-L-arginine methyl ester, inhibitors of nitric oxide (NO) synthase, attenuated the ethanol-induced neutrophil apoptosis. Sodium nitroprusside, a NO donor, also promoted neutrophil apoptosis. Moreover, ethanol enhanced neutrophil expression of inducible NO synthase. In addition, ethanol stimulated neutrophil NO generation. These results suggest that ethanol accelerates neutrophil apoptosis. This effect of ethanol on neutrophil apoptosis seems to be mediated through the generation of NO.

Influence of sample temperature on reflectance photometry and electrochemical glucometer measurements.

OBJECTIVE: A study was conducted to determine the influence of sample temperature on manual reflectance photometers, automatic reflectance photometers, and electrochemical glucometers. RESEARCH DESIGN AND METHODS: Aqueous and blood-based control solutions were tested at temperatures ranging from 25 to 44 degrees C. With the Accu-Chek 3, One Touch, and Satellite G glucometers, multiple glucose determinations were performed on each sample. RESULTS: The results indicate that the manual reflectance photometry glucometer is prominently influenced by variation in sample temperature. The effect of sample temperature is greatest at high glucose levels. CONCLUSIONS: Caution may be required in the interpretation of manual reflectance photometry glucometer measurements in febrile or hypothermic diabetic patients.

Derivation of the Secondary Structure of the ITS-1 Transcript in Volvocales and its Taxonomic Correlations.

Knowledge of secondary structure, formed by the gene spacer regions of the primary transcript of nuclear rDNA cistrons, is lacking for most phyla of eukaryotes. We have sequenced the first internal transcribed spacer region (ITS-1) of multiple representatives of the Volvocales, and from comparisons of these, derived a secondary structure common to the entire group. The secondary structure model is supported by numerous compensating base pair changes located within the paired regions of the stem-loops. Within the morphological species, such as those of Astrephomene and Gonium, the three basal nucleotide pairs of helices are highly conserved in primary sequence, and the single stranded region rich in CCAA is identical in sequence, even when isolates come from all continents of the earth. In other Volvocacean species known to include many pairs of mating types, this same level of conservation is found to correlate with the mating subgroups of the species. Thus a comparable degree of sequence similarity appears to characterize all isolates of a "biological" species; this is valid for taxonomic species only where the biological and taxonomic species levels coincide. In addition, the ITS-1 contains information useful for population analyses, and spacer secondary structure may have additional phylogenetic utility at the level of class or subclass when that information becomes available for other protistan groups.

Effects of cyclodiene compounds on calcium pump activity in rat brain and heart.

The in vitro and in vivo effects of aldrin, dieldrin, and endrin on calmodulin regulated Ca2+-pump activity in rat brain synaptosomes and heart sarcoplasmic reticulum were investigated. All the 3 cyclodiene compounds inhibited both brain synaptosomal and heart sarcoplasmic reticulum Ca2+-pump activity in vitro in a concentration dependent manner. Calmodulin depleted Ca2+-pump activity was insensitive to the action of toxic compounds. Oral administration of pesticides (0.5-10 mg/kg) to rats similarly decreased the Ca2+-pump activity, in addition to decreasing the levels of calmodulin of both brain and heart thus indicating disruption in membrane Ca2+ transport mechanisms. Exogenous addition of calmodulin (1-20 micrograms) could effectively reverse the pesticide induced inhibition. Ca2+-pump activity is more sensitive to the 3 cyclodiene compounds in brain than in heart. The results of the present study indicate that the cyclodiene compounds may produce neurotoxic effects by altering calmodulin regulated calcium dependent events in neurons.

Inhibition of calmodulin activated adenylate cyclase in rat brain by selected insecticides.

Effect of various insecticides on basal and calmodulin (CaM) activated adenylate cyclase activity was studied in solubilized rat brain nuclear and P2 fractions. Our earlier experiments indicated that plictran, chlordecone and other insecticides affect the calcium transport across cell membranes. The present experiments were designed with the assumption that these compounds might exert their neurotoxic action by interfering with CaM (a calcium receptor protein) regulated processes. We have used detergent solubilized adenylate cyclase for our studies, since membrane bound form is not sensitive to externally added CaM. CaM significantly elevated the adenylate cyclase activity in both the fractions and a maximum stimulation of 97% in nuclear fraction and 50% in P2 fraction was observed with 1 microgram of CaM. All the insecticides studied inhibited both basal and CaM activated adenylate cyclase activity in nuclear and P2 fractions to a different extent. A significant inhibition was observed at 0.05 microM and higher concentrations of plictran. Chlordecone and toxaphene inhibited both basal and CaM activated adenylate cyclase in a concentration dependent manner. Although dieldrin and aldrin inhibited basal adenylate cyclase in a concentration dependent manner, they did not exhibit a similar pattern on CaM activated adenylate cyclase. Of all the insecticides studies, chlordecone is more potent in inhibiting both basal and CaM activated adenylate cyclase which is in agreement with the greater neurotoxic action of this compound. These results indicate that all the insecticides studied are potent inhibitors of detergent solubilized adenylate cyclase, and might exert their neurotoxic differential action by interfering with CaM regulated events in central nervous system.

Effect of plictran on beef heart mitochondrial ATPases.

The in vitro effects of plictran on oligomycin-sensitive Mg2+-ATPase and Ca2+-ATPase activities in beef heart mitochondria were studied. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method. ATPase activities were measured by determining the inorganic phosphate released by the hydrolysis of ATP. Plictran inhibited both oligomycin-sensitive (o.s.) Mg2+-ATPase and Ca2+ ATPase activities at nanomolar concentrations. However, plictran did not affect the oligomycin-insensitive (o.i.) Mg2+-ATPase activity at any concentration studied. Substrate activation kinetics revealed that plictran inhibited o.s. Mg2+-ATPase uncompetitively and Ca2+-ATPase non-competitively. These results clearly indicate that plictran affects ATP synthesis and calcium ion transport in beef heart mitochondria.

Rising levels of cardiovascular mortality in Mississippi, 1979-1995.

BACKGROUND: Cardiovascular disease rates are improving in the United States, but not for certain subgroups, especially some African Americans. The objective of the study is to assess current levels and trends in cardiovascular disease mortality in Mississippi. METHODS: Mortality statistics from the U.S. vital statistics system for the period 1979-95 were used. Comparison of age-adjusted mortality rates in Mississippi with the other states for the year 1995 and with the nation as a whole over the period of 1979-95 was performed. RESULTS: Mississippians had the highest age-adjusted cardiovascular disease morality rates in the nation in 1995. Overall, the cardiovascular rates in Mississippi were 37% higher than for the U.S. African American men and women from Mississippi had especially high cardiovascular mortality rates, approximately 50% and 70% higher than their white counterparts, respectively. The higher burden of cardiovascular disease in African Americans from Mississippi was especially marked in the younger age groups. Since about 1984-85, cardiovascular mortality rates in Mississippi have been increasing for African Americans, whereas nationally they have been decreasing. In contrast, cardiovascular mortality rates for whites in Mississippi have been declining, but at a much slower rate than seen nationally. The wide divergence in trends for African American and white men and women over that period in Mississippi has lead to an estimated 19,400 excess cardiovascular deaths. Virtually identical trends were found for heart disease. CONCLUSIONS: Cardiovascular diseases are a major public health problem in Mississippi that is especially severe in African American residents, and the problem is growing worse each year. It is important to identify the determinants of and solutions for this enormous public health problem in Mississippi.

Collection of biological materials in biodiversity prospecting in India: problems and solutions.

Forests are the chief resource for the collection and exploration of biological materials. The past few decades have witnessed a large scale deforestation in India due to substantial pressures generated by population growth, leading to demand for more land for agriculture, urbanization and industrial activities, in addition to increased demand for fuel wood and timber. This has resulted in the loss of soil cover, habitat destruction, environmental degradation and ecological imbalance. This scenario has created a progressive awareness for the conservation and restoration of habitats and, thus, the declaration of many forest areas into protected zones, such as national parks, biosphere reserves, etc., including the protection of some marine areas, by both the National and State Governments. Normally, permission for biological collecting is not granted in these protected areas. In India, forests are a State subject and grant for collection permission is vested with the State Forest Departments. In the absence of any rules, regulations and guidelines, either from National or State Governments, forest authorities impose their terms and conditions, which are arbitrary and even contradictory at times, in the process of granting collecting permits. A set of new rules to be applied throughout the country is needed.

Studies on the association of Aspergillus fumigatus with ocular infections in animals.

The occurrence and aetiological significance of Aspergillus fumigatus, an opportunistic pathogen, have been studied in 93 animals with various ophthalmological problems. A total of 93 eye swabs collected from 35 mules, 26 dogs, 13 fowl, 11 cattle, five buffaloes and three camels were investigated mycologically for the presence of A fumigatus. The pathogen was isolated in pure and heavy growth from the swabs from two dogs, one bull, one mule and one fowl. The fungus was also demonstrated directly in clinical material by the potassium hydroxide technique. A fumigatus could not be cultured from the buffaloes and camels. All the five cases had been treated with broad spectrum antibiotics and cortisone and two had received traumatic injury to the eyes (one mule and a bull). The organism was not isolated in pure culture from the conjunctival swabs of 22 apparently healthy animals (11 dogs, six mules, three fowl and two cattle). Many other saprophytic fungi were recovered in mixed cultures but were considered to be contaminants. The clinical signs and diagnostic criteria of oculomycosis have been discussed.

Screening of Indian plants for biological activity: Part XV.

Alcoholics extracts of 266 botanically identified plant materials from 222 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings. Biological activities have been observed in 89 extracts. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported.

Bioactivity of marine organisms: Part VI--Screening of some marine flora from Indian coasts.

Alcoholic extracts of 50 botanically identified species of marine flora have been screened for a wide range of biological activities. Of these, 2 extracts exhibited anti-amoebic and antiviral activity each, 3 of them had anti-implantation activity; 9 had hypoglycaemic activity while hypotensive activity was associated with 11 extracts; 14 extracts were found to be diuretic and 1 of them had anti-inflammatory activity. Further, 10 of these extracts exhibited 2 types of activities while a combination of 3 and 4 types of activities was observed in one extract each. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported.

Screening of Indian plants for biological activity: Part XIV.

Alcoholic extracts of 300 botanically identified plant materials from 275 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings. Biological activities have been observed in 111 extracts. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported.