Intraperitoneal cisplatin-based chemotherapy for primary treatment of epithelial ovarian cancer.

INTRODUCTION: This study looks at the feasibility of intraperitoneal cisplatin-based treatment in patients newly diagnosed with ovarian cancer in a community hospital setting and provides long-term follow-up of a cohort of patients. METHODS: Sixteen patients with epithelial ovarian cancer were studied. All patients underwent definitive surgical debulking. Patients were scheduled to be treated with six cycles of intraperitoneal cisplatin and either intravenous cyclophosphamide or intravenous doxorubicin at four week intervals. RESULTS: Fifteen patients were evaluable for response. All patients received at least three cycles of intraperitoneal therapy. All patients had an initial clinical response. Nine of 15 patients underwent second-look laparotomy; five of the nine patients had positive second-looks, none had residual macroscopic disease. Of the remaining six patients, five had clinical complete remissions and four are alive without recurrence. CONCLUSION: High-dose intraperitoneal cisplatin-based with sodium thiosulfate protection is generally well-tolerated and possibly an appropriate alternative first-line therapy for selected patients with epithelial ovarian cancer.

A novel and rapid PCR-based method for genotyping human papillomaviruses in clinical samples.

Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5(+)-GP6(+) consensus primer pairs, HPV sequences were amplified by nested PCR from DNA isolated from cervical smear samples. This led to the production of an approximately 140-bp PCR product from the L1 (major capsid) gene of any of the HPVs present in the sample. PCR was performed with a deoxynucleoside triphosphate mixture which resulted in the incorporation of deoxyuridine into the amplified DNA product at positions where deoxythymidine would normally be incorporated at a frequency of about once or twice per strand. Following the PCR, the product was treated with an enzyme mix that contains uracil N-glycosylase (UNG) and endonuclease IV. UNG removes the uracil base from the nucleotide, and endonuclease IV cleaves the phosphodiester bond at this newly formed abasic site, producing fragments of various sizes. By having end labeled one of the amplification primers, a DNA ladder which is analogous to a "T-sequencing ladder" was produced upon electrophoresis of the products. By comparing this T-sequencing ladder to the known sequences of HPVs, the genotypes of unknown HPV isolates in samples were assigned. Data showing the utility of this technique for the rapid analysis of clinical samples are presented.

Cooperative diastereoselectivity of palladium- and platinum-promoted intramolecular [4 + 2] Diels-Alder cycloaddition reactions of 3,4-dimethyl-1-phenylphosphole.

The complexes [(DMPP)2M(CH3CN2)]X2 (DMPP = 3,4-dimethyl-1-phenylphosphole; M = Pd, Pt; X = BF4-, NO3-, ClO4-) react with 2 equiv of the dienophiles N,N-dimethylacrylamide (DMAA), 2-vinylpyridine (VyPy), and diphenylvinylphosphine (DPVP) to form bis-[4 + 2] Diels-Alder cycloaddition products. The [M(DMPP)2(DMAA)2]2+ and [M(DMPP)2(VyPy)2]2+ complexes form exclusively as the cis-geometric isomers, whereas for [M(DMPP)2(DPVP)2]2+, both cis- and trans-geometric isomers are formed. The two Diels-Alder cycloadditions occur sequentially, and the absolute configuration of the first reaction influences the absolute configuration of the second. In all cases, recemic mixtures of the (R,R) and (S,S) diastereomers are formed; none of the meso (R,S) diastereomer is observed. New complexes were characterized by elemental analyses, physical properties, infrared spectroscopy, 1H, 1H(31P), 13C(1H), and 31P(1H) NMR spectroscopy, and, in most cases, X-ray crystallography.

Survival of Listeria monocytogenes in commercial cheese brines.

The survival of Listeria monocytogenes was determined in commercial cheese brines collected from cheese factories in Wisconsin and northern Illinois. Survival of L. monocytogenes inoculated into commercial cheese brines ranged from < 7 d to over 259 d. Survival did not correlate with pH, salt content, nitrogen content, mineral content, or inherent microbial populations but was negatively associated with addition of sodium hypochlorite at the dairy plant. The L. monocytogenes generally survived longer in brines held at 4 degrees C than at 12 degrees C. Sodium hypochlorite or hydrogen peroxide inactivated L. monocytogenes when added to commercial brines in the lab at 10 to 100 ppm or 0.001% to 0.02%, respectively. Addition of 1% potassium sorbate or 1% sodium benzoate also decreased survival of L. monocytogenes. Laboratory filtration of commercial brines had a negative effect on survival in one of three brines tested. The L. monocytogenes did not grow during incubation in any of the commercial brine samples tested.

Respirator cartridge service-life: exposure to mixtures.

Expressions associated with a previously developed procedure to assess respirator cartridge service-life were modified to address the cartridge breakthrough properties of each of individual compounds comprising systems with more than two components. These were applied to specific ternary and quaternary test mixtures. Experimental breakthrough data were collected for (1) acetone/cyclohexane/toluene, (2) ethyl acetate/cyclohexane/toluene, (3) cyclohexane/toluene/ m-xylene, (4) ethyl acetate/cyclohexane/toluene/m-xylene, and (5) acetone/ cyclohexane/toluene/ m-xylene. Data indicate that as an exposure experiment proceeds, a compound that is adsorbed relatively weakly by the carbon bed may be displaced by a more strongly adsorbed component, which may result in a breakthrough concentration for displaced compounds that exceeds the challenge concentration in the mixture. The approach described accounts for the displacement phenomenon and can predict the ratio of the number of displaced molecules to the corresponding number of displacing molecules. Experimental data for each multicomponent system were used to determine values of three parameters (k', tau, and A(m)) for each compound in each challenge system. The value of k' characterizes the rate of adsorption of a compound under applicable experimental conditions, tau indicates the capacity of the charcoal, and A(m) describes the effectiveness of a compound in displacing a previously adsorbed compound. Parameter values were applied to calculate complete breakthrough curves for each compound of each mixture. Calculated curves were compared with corresponding experimental data; reasonable agreement justifies simplifying assumptions incorporated into the application of the approach to mixtures of more than two compounds. The time-dependence of the weight of each compound adsorbed by the carbon was calculated. The service-life of respirator cartridges exposed to multicomponent mixtures depends on the challenge concentration of each component of the system and is significantly influenced by the displacement effect. The adsorption capacity of the carbon and the breakthrough time for weakly adsorbed compounds are decreased significantly by exposure to mixtures.

Photocatalytic detoxification of cyanide and metal cyano-species from precious-metal mill effluents.

Photochemically-induced detoxification of various cyanide species from a selected precious-metal mills tailings was investigated in detail. The studies were conducted in the presence or absence of a titanium (IV) oxide semiconductor photocatalyst utilizing simulated sunlight as the irradiation source. It was established that the cyanide ion (both free and complexed) was photocatalytically oxidized to nitrate via cyanate and nitrite. In addition iron, copper, zinc, mercury and arsenic were stabilized as precipitates. The results obtained may have ramifications for the possible use of solar energy for the efficient treatment of large quantities of precious-metal mill-tailing wastes that contain various cyano-species.

Indirect determination of tetrahydroborate (BH(-)(4)) by gas-diffusion flow injection analysis with amperometric detection.

A rapid, indirect gas-diffusion flow injection analysis (FIA) method with amperometric detection has been developed for the selective and sensitive determination of tetrahydroborate (BH(-)(4)). The injected analyte reduces arsenic(III) to arsine. The arsine formed diffuses through the PTFE (polytetrafluoroethylene) membrane and is quantified amperometrically at a platinum working electrode. The precision of the technique was better than a relative standard deviation of 2.1% at 60 muM levels and better than 0.5% at 0.1 mM, with a throughput of 60 samples/hr. The detection limit of the method was found to be 1 muM (1.5 ng BH(-)(4)) with a linear range up to 1 mM. The dynamic range extends over five orders of magnitude in BH(-)(4) concentration. The effects of working potential, concentration of As(III) and HCl in the reagent stream, type and flow rate of the acceptor solution, temperature and interferents on the FIA signals were studied.

IV fluidmakers: preparation of sterile water for injection in a field setting.

Two approaches have been investigated for generating USP sterile, pyrogen-free water for injection (WFI) from potable water in the field. The first approach utilizes reverse osmosis (RO), ion exchange, a solid matrix filter containing activated carbon and zeta adsorbent, a final 0.2 microns pore size sterilizing filter and a device for transferring the WFI to an IV bag; prototype systems based on three different hand-operated RO units weigh 1.5-3.5 kg and are capable of producing WFI at rates of 1-10 L/hr. Parenteral solutions were made by adding WFI to an IV bag containing concentrated Ringer's lactate. The second approach, still in the breadboard stage, is similar but utilizes a larger ion exchange column in place of the RO unit and a multiport distribution head to fill a set of 18 1-L IV bags. This system, considered to be disposable, is capable of generating water of WFI quality at a fill rate of 0.5 L/min from a pressurized source.

Pulsed, non-thermal, high-frequency electromagnetic energy (DIAPULSE) in the treatment of grade I and grade II ankle sprains.

Acutely sprained ankles represent a frequent and common injury among active duty troops in training, and are a significant source of morbidity with respect to days lost to training. Swelling in the form of periarticular edema limits motion, causes pain, prevents wearing of normal foot gear, and slows the healing process. Reduction of edema was attempted in acutely sprained ankles by the use of pulsed electromagnetic energy (Diapulse). In a randomized, prospective, double blind study of 50 grade I and II (no gross instability) sprained ankles, a statistically significant (p < 0.01) decrease in edema was noted following one treatment with Diapulse. The application of this modality in acutely sprained ankles could result in significant decreases in time lost to military training.

A theoretical model for respirator cartridge service life for binary systems: application to acetone/styrene mixtures.

A theoretical model, developed previously to assess respirator cartridge service life, was applied to various acetone/styrene binary assault systems. Experimental data, collected for several binary mixtures differing only with respect to the concentration of each of the two compounds, were interpreted in terms of the model. Styrene concentrations varied from 228 to 1578 ppm; the range of acetone concentrations was 92-985 ppm. The specific influence of the compound assault concentrations on respirator cartridge service life was carefully characterized, as break-through curves were generated for both acetone and styrene for each of several different binary systems. Specifically, experimental data for each system were used to determine values of the following theoretical parameters: k'1, tau 1, k'2, tau 2, and Am. These parameters were employed with the theory to generate complete theoretical breakthrough curves and to determine the time-dependence of the weight of each compound adsorbed by the respirator cartridge carbon bed. An interesting phenomenon observed for the acetone/styrene systems was the displacement (from the carbon) of previously adsorbed acetone molecules by styrene molecules. Acetone breakthrough was observed first in each of the systems studied. Following the onset of this breakthrough, the acetone breakthrough concentration was enhanced by the displacement of acetone from the carbon bed by the adsorption of styrene. The theoretical model accurately predicts both this enhancement and the associated breakthrough characteristics of styrene. In addition, the theory is capable of predicting the ratio of the number of displaced acetone molecules to the corresponding number of displacing styrene molecules. For these studies, this ratio ranged from 0.3 to 0.7. The service life of respirator cartridges exposed to acetone/styrene mixtures depends on the assault concentration of each compound and is significantly influenced (shortened) by the displacement phenomenon.

Breakthrough time and adsorption capacity of respirator cartridges.

A model developed in previous studies was applied to investigate the respirator cartridge contaminant breakthrough of 121 different chemical compounds. Included in this set of 121 contaminants are representative examples of various types of organic compounds, (e.g., acetates, ketones, aromatics, alcohols, amines, alkanes, chlorinated hydrocarbons). Intrinsic to the model are two important parameters, k' (a rate constant) and tau (50% breakthrough time). Values of the two parameters pertinent to an assault concentration of 1000 ppm were determined for each of the 121 organic compounds. These values were used to calculate the breakthrough time at specified fractional breakthrough as well as the respirator cartridge loading capacity under various conditions. An approach was presented that permits the determination of contaminant loading capacity (on carbon) as a function of breakthrough time at a specified assault concentration. The effect of contaminant assault concentration on the saturation capacity was investigated for various combinations of nine different compounds and three different types of respirator cartridges. Calculated saturation capacity data derived from application of the model compare favorably (+/- 5%) with corresponding experimental data. Saturation capacities calculated by using the model addressed in this study were compared with corresponding results previously calculated by others using the Dubinin adsorption isotherm.

Comparing the medical school curricula followed by students in an independent study program and a traditional one.

This 1988 retrospective study examined the medical school curricula followed by students from two classes using two curricular styles at one medical school. By consulting school records, the authors ascertained the courses actually taken, the number of weeks that students actually devoted to them, and the sequence of courses, both for those students following an independent-study curriculum and for those following a traditional one. These data were compared with the corresponding data concerning the traditional curriculum requirements to determine whether the curricula the students actually followed, in either style, showed any marked difference from the required curriculum. The findings showed that the curricula followed by the independent-study students deviated considerably from both the requirements of the traditional curriculum and also the actual curricula followed by the students using the traditional curriculum, who almost never chose to deviate from the requirements. The independent-study students showed considerable intragroup variation in the ways they organized their curricula, most commonly in eliminating selected formal clerkship or specialty medicine courses, or altering the duration of clerkships. Elective coursework was substituted for formal clerkship experiences in the majority of cases where clerkship courses were eliminated.

Multifocal, synchronous inverted papillomas involving the ureter.

Inverted papillomas involving the upper urinary tract remain a rarely diagnosed phenomenon. A case of bilateral ureteral inverted papillomas is presented. The treatment and diagnosis of this lesion remain a challenge.

Arsenic levels in fingernails as a biological indicator of exposure to arsenic.

The analysis of urine, blood, and hair has been used previously to monitor occupational exposure to arsenic (As). Although arsenic is normally present in human fingernails (usually as a result of dietary factors), this study evaluated the potential use of levels of arsenic in fingernails as a biological indicator of occupational exposure to this element. Air samples and fingernail clippings were obtained from individuals with no exposure and high, medium, and low exposure. A washing technique, previously developed to remove exogenous arsenic from hair, was modified to wash the fingernail samples collected in this study. It was demonstrated that 98% of exogenous arsenic was removed from these nails. A high correlation coefficient (r = 0.89) was observed in a comparison of the mean air arsenic concentrations of each exposure group with corresponding arsenic levels in fingernails. From the data collected, an equation was derived to estimate the air arsenic exposure level for a worker from the arsenic content of fingernails: air arsenic concentration (micrograms As/m3) = 1.79 x fingernail arsenic level (micrograms As/g nail)-5.9.

Contaminant breakthrough: a theoretical study of charcoal sampling tubes.

A previously developed theoretical model was applied to investigate contaminant breakthrough on charcoal sampling tubes. Associated with the model are two important theoretical parameters. These parameters are k' (a rate constant) and tau (the time required for 50% contaminant breakthrough). In this study, values of K' and tau were determined for n-heptane at five different concentration levels in air: 98, 117, 234, 330, and 988 ppm. These values were used along with pertinent theoretical considerations to calculate the entire (0-100%) breakthrough curve (plot of percent breakthrough versus time) regarding the adsorbance of n-heptane on charcoal sampling tubes. In addition, available experimental data for perchloroethylene, isobutyl acetate, ethyl acetate, and dichloromethane were used in conjunction with the theory to generate theoretical breakthrough curves over the entire range of 0 to 100%. In each case, calculated theoretical breakthrough curves are in remarkable agreement with corresponding experimental data. With the use of an additional theoretical parameter, a, the theory was extended to calculate the weight of contaminant collected on a single element (section) of a charcoal sampling tube at 10% breakthrough and at each of several different contaminant assault concentrations.

Effects of humidity and contaminant concentration on respirator cartridge breakthrough.

A model described previously was developed further to examine the effect of both test humidity and contaminant assault concentration on respirator cartridge service life. The model emphasized the characterization of cartridge performance in the range of 0% to 50% breakthrough. This study specifically addressed a contaminant concentration range of 250-2000 ppm and test humidities ranging from 0% to 80%. The preconditioning humidity was fixed at 50%. The compounds studied were benzene and methyl chloroform. Two parameters, k' and tau, were described and values of these parameters were determined for each of several different sets of experimental conditions. The determined values of k' and tau were applied using derived expressions to generate each of several complete breakthrough curves for benzene and for methyl chloroform at specified contaminant assault concentrations and test humidities. The effect of humidity on the value of an additional theoretical parameter, a, was investigated. Values of this parameter and the parameters, k and K", were determined for specific test conditions. These values were substituted into pertinent expressions to produce a complete set of breakthrough curves (each curve corresponding to a particular contaminant assault concentration) for a given compound at a fixed test humidity. Several examples of breakthrough curves were generated for methyl chloroform. The results derived from the study agreed with corresponding experimental data.

Bleeding patterns with low-dose, monophasic oral contraceptives.

Cycle control over 12 months with low-dose oral contraceptives (OCs) was analyzed using calendars of bleeding on pill-taking days 1 through 21 (intermenstrual bleeding; IMB). One preparation contained 0.5 mg norethindrone and 0.035 mg ethinyl estradiol (NET + EE), the other 0.3 mg norgestrel and 0.03 mg ethinyl estradiol (Ng + EE). Half the subjects had previously used OCs containing greater than or equal to 0.05 mg estrogen (switch-over); the others had not previously used OCs for 2 months or more (fresh). Fresh subjects reported more IMB than switch-over subjects, especially during the first three cycles; IMB decreased over time for both groups. Ng + EE subjects had fewer IMB episodes during the early cycles than NET + EE subjects. Daily incidence of IMB formed a characteristic W-shaped curve in the NET + EE subjects that was most apparent in early cycles.