Choosing an equivalent replacement column for a reversed-phase liquid chromatographic assay procedure.

The column selectivity parameters (H, S*, A, B and C) described in the preceding paper [L.R. Snyder, A. Maule, A. Heebsch, R. Cuellar, S. Paulson, J. Carrano, L. Wrisley C.C. Chan, N. Pearson, J.W. Dolan, J.J. Gilroy, J. Chromatogr. A 1057 (2004) 49-57] can be used to compare columns in terms of selectivity. A detailed procedure for such column comparisons is presented here, and evaluated by its use in finding suitable replacement columns for 12 different routine separations performed in five different pharmaceutical analysis laboratories.

Surgery versus radiation therapy as single-modality treatment of tonsillar fossa carcinoma: the Roswell Park Cancer Institute experience (1971-1991).

OBJECTIVE: To compare the efficacy and treatment outcomes in patients with tonsillar fossa cancer using surgery or radiation as a single modality therapy. METHODS: From 1971 to 1991 239 patients with oral pharyngeal cancer were treated at Roswell Park Cancer Institute. Of these patients 90 had tonsillar carcinoma. Seventy-six of these patients received either surgery (SA) (n = 56) or radiation therapy (RA) (n = 20) as single-modality therapy and are the subject of this review. All patients in the radiation arm of this review were surgical candidates who declined primary surgical therapy. RESULTS: Sixty-three percent of the SA and 80% of the RA treatment groups presented with either stage III or stage IV disease (P < or = .05). Forty-seven percent of the SA group and 52% of the RA patients had clinically positive regional disease at initial presentation. There was a predictable pattern of nodal presentation, with level II the most frequently involved region. The rate of occult metastasis was 27% and was evenly distributed between T1 and T4 disease. The overall local control rate in the SA group was 75%, compared with 60% in the RA group (P value was not significant). The disease-specific survival (all stages) was 61% in the SA group and 37% in the RA group (P < or = .05). The disease-free survival for stage III and stage IV disease in the SA group was 47% and in the RA group 27% (P < or = .05). Survival measured against clinical response to radiation therapy, in complete responders (all stages) was 83%; by contrast there were no survivors past 24 months in the partial response group (P < or = .001). CONCLUSION: The results from this study suggest that for early disease (stage I/II), surgery or radiation therapy as single-modality treatment is equally effective. For advanced disease radiation therapy is inferior to surgery as a single-modality treatment, as measured by ultimate survival and the local control of disease. There is, however, a subset of patients with advanced disease who respond to radiation therapy and whose survival is equivalent to our surgical cohort of patients.

Follow-up study on the carcinogenicity of vinyl chloride and vinylidene chloride in rats and mice: tumor incidence and mortality subsequent to exposure.

Carcinogenic and other toxic effects in rats and mice were examined during a 12-mo period following exposure to vinyl chloride (VC) or vinylidene chloride (VDC). Exposure of male and female mice to 50, 250, or 1000 ppm VC for 6 h/d, 5 d/wk, for 1, 3, or 6 mo resulted in increased numbers of deaths and increased moribundity at all dose levels during the exposure and postexposure periods, as compared with air-exposed controls. Similar observations were made with rats after 1, 3, 6, or 10 mo exposure to VC. Cumulative tumor incidence at various organ sites also increased in both species during the postexposure period in proportion to dose or duration of exposure at higher dose levels. However, except for mammary gland tumors in female mice, no significant increase in cumulative tumor incidence occurred in either species at 50 ppm VC or 55 ppm VDC, regardless of duration of exposure. These results suggest that exposure to vinyl halides at dose levels lower than those that elicit a significant increase in cancer incidence during the lifetime of the animal may, nonetheless, increase the risk of early death or moribundity from toxic pre- or subcarcinogenic effects. At dose levels higher than those consistent with the physiological defense or repair capabilities of the cell, ultimate tumor incidence becomes proportionate to length of exposure and may reflect the number of carcinogenic events elicited during the exposure period.

Influence of increasing age on lethality induced by carbon monoxide or hypoxic hypoxia.

Mice ranging in age from 2 to 150 days of age were exposed to 2,000 ppm carbon monoxide (CO) or 7.5% O2. 2-day-old mice were more resistant than older animals to the lethal effects of both CO and hypoxic hypoxia. The oldest age group (150 days) were also found to be more resistant than young adult mice to the lethal effects of both CO and hypoxic hypoxia. The role of body temperature in the age-dependent susceptibility was studied by altering the environmental temperature. Neonatal mice remained resistant to the lethal effects of CO until the environmental temperature reached 35 degrees C at which time the death rate of neonatal mice equaled that of the adult mice in 30 degrees C environment.

Carcinogenicity of vinyl chloride and vinylidene chloride.

Exposure of mice to 50, 250, or 1000 ppmm of vinyl chloride (VC) in the air for 6 h/d, 5 d/wk, caused a high incidence of bronchioloalveolar adenoma, mammary gland tumors, and hemangiosarcoma. Mammary gland tumors occurred in the females and included ductular adenocarcinoma and squamous and anaplastic cell carcinomas with metastasis to the lung. Hemangiosarcoma occurred in the liver and, to a lesser extent, in various other organs. The incidence and severity of these tumors increased with the concentration of VC and the length of exposure. Malignant lymphoma involving various organs was observed in several mice. Rats were more resistant to the carcinogenic effects of VC. Exposure of rats to 250 or 1000 ppm of VC caused hemangiosarcoma in the liver. Many rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Extrahepatic hemangiosarcoma also occasionally occurred in other organs. Exposure to 55 ppm of vinylidene chloride (VDC) caused hepatic hemangiosarcoma and probably bronchioloalveolar adenoma in mice. Hemangiosarcoma also occurred in the mesenteric lymph node or subcutaneous tissue in two rats exposed to 55 ppm of VDC.

Effect of various treatments on toxicity of inhaled vinylidene chloride.

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various treatments to alter parameters of toxicity was evaluated. Mice were more sensitive than rats both to the acute lethal and hepatotoxic effects of VDC. Disulfiram treatment reduced the acute lethal and hepatotoxic effects of inhaled VDC and reduced the levels of covalent bound radioactivity in the liver and kidney after the intraperitoneal administration of 14C-VDC. Treatment with diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.

Inhalation toxicity of vinyl chloride and vinylidene chloride.

Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month, mice exposed to 1000, 250, or 50 ppm of VC became lethargic, lost weight quickly, and died. Only a few mice exposed to 50 ppm survived for 12 months. Pulmonary macrophage count was elevated in some mice. There was a high incidence of bronchiolo-alveolar adenoma, mammary gland tumors including ductular adenocarcinoma, squamous and anaplastic cell carcinomas with metastasis to the lung, and hemangiosarcoma in the liver, and, to a lesser extent, in some other organs. The incidence of these tumors quickly increased, and the severity was in direct proportion to the levels of VC and the length of exposure. Malignant lymphoma involving various organs was observed in a few mice. Rats were more resistant to the toxic effects of VC. Exposure to 1000 ppm slightly depressed the body weight of the females. Exposures of 250 or 1000 ppm caused a number of deaths and hemangiosarcoma in the liver starting the ninth month. Most rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Hemangiosarcoma occasionally occurred in other tissues of one or two rats exposed to 50 ppm or higher level of VC. Exposure of mice to 55 ppm of vinylidene chloride (VDC) also caused a few acute deaths and a few hepatic hemangiosarcomas. Inflammatory, degenerative, and mitotic changes occurred in the liver. No mouse exposed to VDC developed any mammary gland tumors. Several mice had bronchioloalveolar adenoma. Exposure of rats to 55 ppm of VDC slightly depressed the body weight. Hemangiosarcoma occurred in the mesenteric lymph node or subcutaneous tissue in two rats.

A dominant lethal study in male rats after repeated exposures to vinyl chloride or vinylidene chloride.

Male CD rats were exposed 6 hr/day for 5 days/wk to 0, 50, 250, or 1,000 ppm of vinyl chloride or 55 ppm of vinylidene chloride. Starting on week 11 of exposure, these males were mated with untreated females. There was no evidence of either preimplantation loss or postimplanation loss in pregnant females that resulted from these matings. Consequently, it was concluded that these exposures did not produce germinal mutation, as manifested by a dominant lethal effect, in male rats.

Toxicity of vinylidene chloride in mice and rats and its alterations by various treatments.

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various compounds to alter parameters of toxicity was evaluated. Mice were more sensitive than rats to the lethal, hepatotoxic, and renal toxic effects of VDC. Disulfiram protected mice from these toxic effects of inhaled VDC and reduced the levels of covalently bound radioactivity in the liver and kidney after the ip administration of [14C] VDC. Diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.

Effect of potassium cyanate on carbon monoxide and hypoxic hypoxia-induced lethality.

Pretreatment of mice with potassium cyanate for 15 days resulted in a significant increase in hemoglobin-oxygen affinity (decrease in P 50) and a significant protection against hypoxic hypoxia-induced lethality. However, cyanate pretreatment had no significant effect on carbon monoxide-induced lethality. Oxygen consumption in cyanate-treated mice was significantly lower than in controls in room air but not different in hypoxic environments. Whether the protective effect of cyanate on hypoxic hypoxia-induced lethality is due to the increase in hemoglobin-oxygen affinity or attributable to a non-hemoglobin-related action of cyanate remains unresolved. Regardless, the need exists to reevaluate the current concept that changes in hemoglobin affinity for oxygen correlate with susceptibility to hypoxemic states. In addition, data presented together with previous findings support the concept that carbon monoxide lethality is not solely attributable to a carboxyhemoglobin-induced hypoxemia.

Influence of carbon monoxide, hypoxic hypoxia or potassium cyanide pretreatment on acute carbon monoxide and hypoxic hypoxia lethality.

Pre-exposure of mice to 500 or 1000 ppm of carbon monoxide (CO) for 4 hours resulted in a significant decrease in lethality induced by exposure to 2500 ppm of CO 24 hours later. Pre-exposure to CO had no effect on lethality induced by hypoxic hypoxia (low inspired O2 tension) or potassium cyanide (KCN). Pre-exposure to 10% O2 for 4 hours significantly decreased lethality induced 24 hours later by CO or 7% O2 exposures lethality induced 24 hours later by CO or 7% O2 exposures but had no effect on KCN-induced lethality. Pretreatment with a nonlethal dose of KCN had no significant effect on lethality induced 24 hours later by exposure to CO (2500 ppm), 7% O2 or KCN. The alterations in CO lethality were not associated with alterations in carboxyhemoglobin levels. Studies of oxygen consumption and indicators of oxygen delivery to tissues (P50 and red blood cell 2,3-diphosphoglycerate) failed to provide any evidence of pretreatment alteration. Examination of blood lactate, pyruvate and lactate/pyruvate ratios in control and pre-exposed mice after a short exposure to 2500 ppm of CO showed significantly lower lactate and lactate/pyruvate ratios in the pre-exposed mice as compared to controls. These data suggest that animals pre-exposed to 1000 ppm of CO and 10% O2 are less hypoxic than non-pre-exposed animals even through their oxygen delivery system is unchanged.