Discrepancies between Viscosity Data for Simple Gases.

It has been known for some time that Kestin and his co-workers have reported dilute gas viscosity coefficients which differ from the usually accepted values. Recent work from the Los Alamos Scientific Laboratory supplements Kestin's results. We show that there is no evidence for not accepting this different data. We feel that the whole subject of dilute gas viscosity measurements above room temperature should be reexamined both from the experimenter's and correlater's viewpoints. There is evidence that published tables may be incorrect by as much as 10 percent above 600 degrees K.

Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers.

Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness.

2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents.

In view of the antimalarial activity in mice of 2-acetylpyridine thiosemicarbazones, a series of analogous 1-oxides was prepared for evaluation. Their synthesis was achieved by the reaction of 2-acetylpyridine 1-oxide with methyl hydrazinecarbodithioate to give methyl 3-[1-(2-pyridinyl 1-oxide)ethylidene]hydrazinecarbodithioate (II). Reaction of the latter intermediate with secondary amines afforded the desired 2-acetylpyridine 1-oxide thiosemicarbazones (III). Reduction of the azomethine linkage of II with NaBH4 gave methyl 3-[1-(2-pyridinyl 1-oxide)ethyl]-hydrazinecarbodithioate (IV) whose S-methyl group was then displaced by amines to give a 1-[1-(2-pyridinyl 1-oxide)ethyl]thiosemicarbazide, V. Antimalarial activity of III was evaluated against both Plasmodium berghei in the mouse and Plasmodium falciparum in an automated in vitro test system. In both cases, 2-acetylpyridine 1-oxide thiosemicarbazones were found to be less active than the corresponding de-1-oxide analogues. When compounds V were evaluated against Plasmodium berghei in the mouse, a diminution of activity was similarly seen in comparison to the analogues not bearing the 1-oxide moiety.

Mental health care utilization and expenditures by children in foster care.

OBJECTIVE: To determine the percentage of children with mental health diagnoses and utilization and expenditures of mental health services among children in foster care compared with other children receiving Medicaid, including those with disabilities. DESIGN: Analysis of Medicaid claim and eligibility records in southwestern Pennsylvania for fiscal year 1995. POPULATION: A total of 39,500 children between ages 5 and 17 years continuously eligible for Medicaid in southwestern Pennsylvania were included in the analysis. MAIN OUTCOME MEASURES: Percentage of children with mental health diagnoses and mental and general health care utilization and expenditures classified by participation in foster care and Medicaid eligibility. RESULTS: Children in foster care were 3 to 10 times more likely to receive a mental health diagnosis, had 6.5 times more mental health claims, were 7.5 times more likely to be hospitalized for a mental health condition, and had mental health expenditures that were 11.5 times greater ($2082 vs $181) than children in the Aid to Families With Dependent Children (AFDC) program. Overall, utilization rates, expenditures, and prevalence of psychiatric conditions for children in foster care were comparable with those of children with disabilities. CONCLUSIONS: Children in foster care are significantly more likely to suffer from mental health conditions and use more mental health and general health services than AFDC children. Service use and expenditures are comparable with those of disabled children, suggesting that reimbursement rates and care management for children in foster care need to be reexamined.

Insurance status and recognition of psychosocial problems. A report from the Pediatric Research in Office Settings and the Ambulatory Sentinel Practice Networks.

OBJECTIVE: To examine the effect of insurance status on clinician recognition of psychosocial problems for pediatric primary care visits. DESIGN: A cohort study of 10,250 visits by children 4 to 15 years old for nonemergent care. SETTING: Two large primary care research networks reported data from 172 primary care clinicians in office-based practice. PATIENTS: Ten thousand two hundred and fifty unique children presenting consecutively to participating physicians for nonemergent services with a parent or caregiver. MAIN OUTCOME MEASURE: Children were classified as positive for psychosocial problems if their score on the parent-reported Pediatric Symptom Checklist exceeded the standard cutoff of 28. Clinician recognition was obtained by report as a dichotomous variable. Insurance status was categorized by payor and plan structure. RESULTS: Clinicians did not recognize psychosocial problems for a substantial number of children with scores suggestive of marked psychosocial dysfunction on the Pediatric Symptom Checklist. Insurance type was not associated with rates of recognition. However, provider familiarity with patients, provider discipline, and patient demographics were associated with increased recognition of psychosocial problems. CONCLUSIONS: Differences in treatment among various insurance groups documented in prior studies are not likely to be related to varying recognition rates, but rather to availability and choices of treatment by insurers, families, and clinicians. Continuity of care was the strongest predictor of clinician recognition.

Analysis of dose-response curves for the in vitro susceptibility of Plasmodium falciparum to antimalarials using a pocket computer.

A small pocket computer, Sharp PC-1500, was programmed to analyze the dose-response curves generated by the in vitro assay of antimalarials against field isolates of Plasmodium falciparum. Using nonlinear regression the analysis provided an estimate of the 50% inhibitory concentration with 95% confidence limits and a graph of the data points and regression function line. The pocket computer with the nonlinear regression program offers a powerful, portable, and inexpensive data analysis system suitable for field use.

Evaluation of an in vitro assay system for drug susceptibility of field isolates of Plasmodium falciparum from southern Thailand.

An in vitro assay system has been developed to evaluate the susceptibility of field isolates of Plasmodium falciparum to standard and new antimalarials. The assay used drugs which were serially diluted in the field and determined effective drug concentrations by quantitating schizont maturation after a variable incubation period. Based on the ID50 values, a series of isolates from Yala in southern Thailand were shown to be resistant to chloroquine (187 nM) but only moderately resistant to amodiaquine (23.7 nM), a structurally related 4-aminoquinoline. Five aminocarbinols were evaluated. The parasites were resistant to quinine (219 nM), but comparatively much more susceptible to mefloquine (9.04 nM), halofantrine (1.23 nM), and enpiroline (6.23 nM). The isolates were also relatively sensitive to WR 194,965 (9.04 nM). Two dihydrofolate reductase inhibitors (WR 99,210 and pyrimethamine) were tested. The isolates were comparatively sensitive to a dihydrotriazine, WR 99,210 (2.85 nM). The in vitro values for pyrimethamine (1,870 nM) were higher than the values for the other drugs tested, but were less than values from other regions of Thailand. As compared to a survey conducted in this region four years previously, values for chloroquine, pyrimethamine, amodiaquine, and mefloquine have remained relatively unchanged. However, there was a greater than 20-fold rise in the susceptibility values for quinine, suggesting the introduction of quinine-resistant isolates from eastern Thailand into southern Thailand during this period.

In vitro activity of pyronaridine against field isolates and reference clones of Plasmodium falciparum.

Pyronaridine, a 9-substituted 1-aza-acridine, was assayed for in vitro activity against clinical and field isolates as well as characterized clones of Plasmodium falciparum. The in vitro antimalarial activity of pyronaridine was compared to activities of standard antimalarials against multidrug-resistant isolates of P. falciparum from eastern and northern Thailand using an assay based on the inhibition of schizont maturation. Isolates from eastern Thailand (n = 30) were susceptible to pyronaridine (IC50 8.40 nM), mefloquine (IC50 6.97 nM), and amodiaquine (IC50 12.7 nM) and resistant to chloroquine (IC50 361 nM), quinine (IC50 388 nM), and pyrimethamine (IC50 11,800 nM). The isolates from northern Thailand (n = 7) showed no statistical difference in susceptibility to pyronaridine (IC50 10.1 nM), amodiaquine (IC50 7.29 nM), and mefloquine (IC50 5.48 nM); however, isolates were significantly more susceptible to chloroquine (IC50 167 nM), quinine (IC50 248 nM), and pyrimethamine (IC50 1,980 nM). These data suggest a lack of cross-resistance between pyronaridine and either chloroquine, quinine, or pyrimethamine. Using the same assay system the in vitro activity of pyronaridine was evaluated against isolates from treatment failures of mefloquine or enpiroline from eastern Thailand. The IC50 values for mefloquine against five recrudescent isolates were significantly higher (IC50 16.4 nM) than the field isolates collected from the same region (IC50 6.97 nM); however, there was no significant difference in the pyronaridine susceptibility between the isolates from the field study (IC50 8.89 nM) and the isolates from the treatment failures (IC50 8.40 nM). These observations suggest a lack of cross-resistance to mefloquine following treatment failure with either mefloquine or enpiroline.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro and clinical correlates of mefloquine resistance of Plasmodium falciparum in eastern Thailand.

A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and after treatment failure with mefloquine. Patterns of drug sensitivity to standard and new antimalarials were characterized by using an in vitro assay based on the inhibition of schizont maturation. In vitro levels of mefloquine sensitivity of isolates were correlated with clinical treatment failures. In vitro parasite resistance to mefloquine is defined as an inhibitory dose-50 value greater than 20 nM. For isolates collected prior to treatment, there was no significant difference in mefloquine sensitivity patterns between subsequent successes and failures, suggesting that mefloquine treatment failures could not be predicted based on in vitro sensitivity of pretreatment isolates. A series of paired isolates were collected both prior to treatment with mefloquine and after recrudescence. Recrudescent isolates showed significant decreases in sensitivity to mefloquine, WR 194965, enpiroline, and halofantrine; no significant changes in sensitivity to amodiaquine, qinghaosu, and pyrimethamine; and an increase in sensitivity to chloroquine.

A comparison of the in vitro activities of amodiaquine and desethylamodiaquine against isolates of Plasmodium falciparum.

The antimalarial activities of amodiaquine, the desethyl metabolite of amodiaquine, chloroquine, and mefloquine were evaluated against 35 field isolates of Plasmodium falciparum collected from eastern Thailand, October-December 1985, to define patterns of cross-resistance among these compounds. The assay system was based on the in vitro inhibition of schizont maturation. The parasites were generally sensitive to mefloquine (mean 50%-inhibitory concentrations = 9.98 nM) and highly resistant to chloroquine (IC50 = 313 nM). The mean in vitro activity of desethylamodiaquine (67.5 nM) was approximately 3.5 times lower than that of amodiaquine (18.2 nM). There was a significant rank-order correlation between the IC50S of desethylamodiaquine and chloroquine, but not between amodiaquine and chloroquine, which suggests that the apparent cross-resistance between chloroquine and amodiaquine observed in clinical studies may be more closely related to the cross-resistance between chloroquine and the metabolite rather than between chloroquine and the parent compound. Isolates with IC50 values of amodiaquine greater than 20 nM demonstrated a high degree of correlation with values of desethylamodiaquine; however, it was not possible to accurately predict the sensitivity to desethylamodiaquine of isolates which had IC50 values of amodiaquine of less than 20 nM.

Analysis of resistance to pyrimethamine/sulphadoxine of isolates of Plasmodium falciparum from Eastern Thailand.

The in vitro susceptibility of five field isolates of Plasmodium falciparum from the region of the Thai-Kampuchean border to pyrimethamine, sulphadoxine, and their combination, was determined using a microtitre test system and media deficient in p-aminobenzoic acid and folic acid. Two-fold serial dilutions of pyrimethamine ranging from concentrations of 8.0 to 0.125 microM and sulphadoxine ranging from 800 to 50 microM were evaluated for antimalarial activity. Viability was based on the maturation of the ring stages to normally-appearing schizonts. Tested singly the parasites had an average ID90 of 3.82 microM for pyrimethamine and greater than 800 microM for sulphadoxine. Analysis of the drugs interaction showed maximum potentiation at approximately 0.8 microM of pyrimethamine and 80 microM of sulphadoxine. These results suggest that resistance to Fansidar is due to the resistance to both components. Although there was a potentiating effect it was probably not sufficient enough for the drugs to be effective in vivo. This may, in part, explain the reduction in clinical cures with the sulphadoxine-pyrimethamine combination in eastern Thailand.

Partial purification of amastigotes from cutaneous lesions of American leishmaniasis.

Amastigotes of Leishmania mexicana, L. mexicana amazonensis, L. brasiliensis, and L. enriettii were isolated from lesions in infected animals. Numbers of amastigotes recovered ranged from 1 X 10(7) to 7 X 10(8), depending on the strain of leishmania. Trypsinization disassociated the lesions and released the parasites. After 18 to 24 hr incubation at 37 C in tissue culture media with antibiotics, many of the intact host cells attached to the flask. Amastigotes were collected from the media in relatively pure preparations. Electron microscopy revealed no morphological alterations of the amastigotes and minimal contamination by membranes and cell fragments.

In vitro mefloquine resistance of Plasmodium falciparum isolated from the Burmese border region of Thailand.

The in vitro susceptibility of twenty isolates of Plasmodium falciparum from Tha Song Yang, Tak province, Thailand were determined. The isolates were resistant to chloroquine (IC50 = 220 nM; MIC = 762 nM), quinine (IC50 = 252 nM; MIC = 1010 nM), and pyrimethamine (IC50 = 16400 nM; MIC = 43100 nM) but generally sensitive to mefloquine (IC50 = 6.90 nM; MIC = 20.9 nM) and halofantrine (IC50 = 8.73 nM; MIC = 2.71 nM). Two isolates were identified which appeared resistant to mefloquine (IC50 = 23.1 nM; MIC = 56.6 nM). These isolates may represent an extension of a population of parasites from eastern Thailand.

The family APGAR and psychosocial problems in children: a report from ASPN and PROS.

BACKGROUND: Our study examined whether the lack of social support as measured by the Family APGAR was related to parents' and physicians' identification of child psychosocial problems and sociodemographic and symptom characteristics of the children screened. METHODS: The parents of 9626 children, ages 4 to 15 years, seen for outpatient medical visits participated in this national study. Parents completed the Family APGAR and the Pediatric Symptom Checklist (PSC), a measure of psychosocial dysfunction. Physicians rated the presence of a new or recurrent psychosocial problem in the child. RESULTS: Children from families with a lack of social support were 4.3 times as likely to receive scores indicating impairment on the PSC and 2.2 times as likely to be identified as having psychosocial problems by physician report. Families with low social support were significantly more likely to report low parental educational achievement, single parent status, and a history of mental health services for the child. Fifty percent of children from families with low social support were identified as having a psychosocial problem by either the PSC or physician rating, or both; however, only 21% of the children identified with psychosocial impairment by these two measures had scores indicating poor family functioning on the Family APGAR. CONCLUSIONS: A lack of family social support is associated with child psychosocial dysfunction as assessed by two different measures. However, the Family APGAR was not a sensitive measure of child psychosocial problems, and thus it supplements, but does not replace, information concerning the child's overall psychosocial functioning.

Analogues of N-benzyloxydihydrotriazines: in vitro antimalarial activity against Plasmodium falciparum.

The antimalarial activities of a series of chlorophenyloxyalkoxy and chlorophenalkoxy N-substituted diamino-dihydrotriazines were determined in vitro against three strains of Plasmodium falciparum (Malayan Camp, Vietnam Smith, FCB) with diverse levels of resistance to chloroquine, pyrimethamine, and cycloguanil. Parasite viability was assayed by the inhibition of the uptake of radiolabelled hypoxanthine. Most of the ID-50S of these compounds were less than 1.0 ng ml-1. Consistent differences in sensitivities to these compounds were observed and appeared to be strain related. The Malayan Camp was the most sensitive and Vietnam Smith was the least sensitive. These differences appeared to be related primarily to an inherent sensitivity of a particular strain to the series of analogues examined rather than to a pattern of cross-resistance to chloroquine, pyrimethamine, or cycloguanil.