Minor furocoumarins of Murraya koenigii.
Xanthotoxin, isobyakangelicol, phellopterin, gosferol, neobyakangelicol, byakangelicol, byakangelicin and isogosferol are reported as minor furocoumarins of Murraya koenigii seeds.
Furocoumarins↗
Biomedical subjects
J Reisch
Publications and source records attributed to J Reisch.
Protease inhibitor-based therapy is associated with decreased HIV-related health care costs in men treated at a Veterans Administration hospital.
BACKGROUND: Protease inhibitor (PI) therapy for HIV infection is associated with decreased rates of opportunistic infections and death. Statistical models predict that decreased complications will be associated with decreased hospitalization costs. A recent report suggested that the decrease in the HIV hospitalization costs were offset by increases in demand for outpatient services. We performed a study of hospital use and HIV-associated health care costs in our center to determine the following: whether PI therapy is associated with decreased inpatient use; whether PI therapy is associated with decreased outpatient use and costs; whether decreased HIV health care costs are associated with increased use of nucleoside analogues. METHODS: The Dallas Veteran Affairs Medical Center provides comprehensive inpatient and outpatient HIV care and thus can evaluate the relation between inpatient and outpatient costs. The mean monthly number of hospital days, Infectious Diseases clinic visits, emergency department visits, other outpatient clinic visits, inpatient costs, outpatient costs, and PI costs were determined from January 1, 1995 through July 31, 1997. This time period was then divided into three intervals. Comparisons of PI use and HIV-related health care costs were during the three intervals was performed using analysis of variance (ANOVA). Significant differences between the baseline characteristics were further analyzed through multiple linear regression. RESULTS: A decrease in hospital days, and all outpatient visits including emergency visits, and HIV clinic visits was determined. No difference was found in the rate of use of other outpatient services. The per patient costs of HIV care decreased from a monthly average of $1905 U.S. in the first interval to $1122 U.S. in the last interval (p < .01). Linear regression demonstrated an inverse relation between PI use and total HIV costs (B=-0.67, p=.00, adjusted R2=0.52) but no relation between nucleoside use, stage of disease or financial class. CONCLUSIONS: PI therapy is associated with decreased hospital days and use of outpatient services. Total patient costs decreased, but a concomitant rise in outpatient costs took place. This increase was primarily a result of increased costs of acquiring PI. Increases in the number of nucleoside agents prescribed were not associated with decreased costs.
Adult↗
Pediatric phase I drug tolerance: a review and comparison of recent adult and pediatric phase I trials.
PURPOSE: We evaluated the ratio of pediatric to adult maximum tolerated doses (MTDs) from 70 Phase I studies conducted between 1975 and 1995. The aim of this study was to determine whether previously observed differences in drug tolerance between adult and pediatric Phase I patients have persisted over the 20-year period of this analysis. PATIENTS AND METHODS: Phase I trials of pediatric and adult patients with solid tumors as the predominant diagnosis and sharing similar dosing regimens were evaluated. For consistent comparison between Phase I studies, the MTD was defined as the drug dose one level below that yielding dose-limiting toxicity in >30% of patients. The ratio of pediatric to adult MTDs was calculated and plotted chronologically by year of pediatric study closure. Statistical evaluation of MTD ratios included regression and correlation analysis. The extent of therapy before Phase I study entry was also examined. RESULTS: Ninety-three Phase I studies were reviewed. Twenty-one drugs (70 studies) met our criteria for paired review of MTDs and analysis of the variation of ratio with time. The pediatric to adult MTD ratios ranged from 0.4 to 2.8, with a median of 1.2. Regression analysis of the ratio of MTD versus date of pediatric study closure supports a linear relationship of decreasing ratio with time (p<0.01). Analysis of the regression line predicts MTD ratios of 2.02 and 0.76 for 1974 and 1995, respectively. Of patients included in this analysis, 37.1% and 68.6% of adult and pediatric patients, respectively, were considered to have been heavily pretreated before study entry. A significant (p<0.001) downward trend with time was observed in the proportion of adult patients entering Phase I studies who had received both radiation and chemotherapy. CONCLUSIONS: The results of this review continue to show an equal or greater drug tolerance in the pediatric population when compared with adult patients for most drugs studied during Phase I trials. However, there appears to be significant trend of decreasing differences in drug tolerance between pediatric and adult Phase I patients with time, as defined by the descent of the MTD ratio toward values <1.0. Mechanisms to explain greater drug tolerance in children and the observation of decreasing maximum tolerated dose ratios with time are discussed. Limited data suggest that changes in degree of therapy before Phase I study entry may be influencing the MTD ratio.
Adult↗
Dimerisation of levonorgestrel in solid state ultraviolet light irradiation.
UV-irradiation of levonorgestrel (1) in the crystalline state under a nitrogen atmosphere yielded its dimer, [17 alpha[1R-(1 alpha,2 beta,4a beta,4b alpha,10a alpha)]]-13-ethyl-17- [4- (2-ethyl-1,2,3,4a,4b,5,6,7,9,10,10a-dodecahydro-7-oxo-1-phenant renyl)-1- methylen-2-oxo-butoxy]-18,19-dinorpregna-4-en-20-in-3-one(3) , as the principal photoproduct. It was characterized from its spectral and analytical data. The single crystal X-ray crystallographic data of 1 indicated the possibility of its photochemical dimerisation.
Crystallography, X-Ray↗
Photostability studies of ouabain, alpha-acetyldigoxin and digoxin in solid state.
Ouabain, alpha-acetyldigoxin and digoxin were subjected to irradiation using different light sources in crystalline state and their respective yields of photoproducts were determined densitometrically. alpha-Acetyldigoxin was found to be less stable than digoxin yielding a higher percentage of photoproducts under each light source examined. Ouabain showed photostability under the conditions of investigation.
Acetyldigoxins↗
Detection and localization of autofluorescent substances in thymus tissue of sheep.
An oxygenated sterol was detected by chemical analysis of sheep thymus lipid extracts. It was characterized as 7 beta-hydroxycholesterol, which is well known for its biological activity. Using fluorescence microscopy, attempts were made to correlate this substance to particular histological structures of the thymus tissue. Microscopy revealed an intense yellow-green primary fluorescence distributed throughout the entire thymic parenchyma, which was predominant in the cortico-medullary junction, the vicinity of the Hassall's bodies and the subcapsular space. This indicated an accumulation of the fluorogenic substance in special tissue structures of sheep thymus. This result can be assumed as specific for the thymus, since such primary fluorescence was absent from other simultaneously investigated organs, such as the adrenal.
Aging↗
[7 beta-hydroxycholesterol, a ubiquitous signal substance in thymus tissue?].
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Animals↗
Serial measurements of GFR in infants using the continuous iothalamate infusion technique. Southwest Pediatric Nephrology Study Group (SPNSG).
We undertook a preliminary study to determine if a clinical trial was feasible that would compare the effect of a low protein vs a control formula on GFR and growth in infants with congenital renal insufficiency (CIo < 55 ml/min/1.73 m2). In this report from the Infant Diet Protein Study, we describe validation of a method using the plasma clearance of iothalamate (CIo) as an estimate of glomerular filtration rate (GFR) and results of the preliminary study relating to renal function. The plasma CIo method was validated as an accurate estimate of GFR by showing it to be the same as the plasma clearance of inulin (CIn). In the preliminary study infants who qualified for the study were randomly assigned to a low protein or control formula and were followed from 8 to 18 months of age. CIo was measured at 8, 14 and 18 months of age in 21 of the infants and at 8 and 18 months of age in all twenty four infants that entered the study. Average absolute GFR in the 24 infants increased in the 10 month period from 5.3 +/- 2.7 to 7.6 +/- 4.5 ml/min. The percent increase in GFR was no different in infants whose GFR at 8 months of age was severely reduced from those whose GFR was only moderately reduced. When adjusted for age and body size, GFR did not change. Change in mean CIo or serum creatinine (SCr) from 8 to 18 months of age between the infants in each diet groups was not different. We conclude that a clinical trial enrolling more infants and extending the study period is necessary to evaluate dietary protein effect.
Age Factors↗
[Direct fluorimetric identification of 7-beta-hydroxycholesterol in sheep thymus].
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Animals↗
[Synthesis and cytostatic actions of 10- and 11-nitronoracronycins, molecular variations of cytostatically active acronycine].
The syntheses of 11- and 10-nitronoracronycine (10 and 11) from 1,3-dihydroxy-10-methyl-5-nitroacridinone (7) or 1,3-dihydroxy-10-methyl-6-nitroacridinone (8), respectively, and 2-chloro-2-methyl-3-butyne are reported. In screening tests with the transplantation tumor leukemia P 388 10, 11, 7 and 1,3-dimethoxy-10-methyl-6-nitroacridinone showed cytotoxicity. 8 and 1,3-dimethoxy-10-methyl-nitroacridinone (5) proved to be inactive.
Acronine↗
[The light sensitivity of corticosteroids in crystalline form. Photochemical studies. 59. (1)].
The light sensitivity of corticosteroids in the solid state have been investigated and the photodecomposition rates of the compounds have been estimated by HPLC. After 48 h UV-irradiation desoxycortone acetate, hydrocortisone, hydrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone and triamcinolone acetonide decompose between 20 and 50%. Cortisone acetate, prednisone and fluocinolone acetonide show photostability in contrast to requirements of the Pharmacopeia for light protections.
Adrenal Cortex Hormones↗
Synthesis of some new hydrazide-hydrazones, thiosemicarbazides, thiadiazoles, triazoles and their derivatives as possible antimicrobials.
The title compounds were prepared by reacting [(4,5-diphenyl-1H-imidazol-2-yl)thio]acetic acid hydrazides 6 and 7 with aromatic aldehydes to give the corresponding hydrazones 6a-m and 7a-d or with isothiocyanates to afford the corresponding thiosemicarbazides 8a-c and 9. 8a-c and 9 were cyclized into triazoline-5-thiones 10a-c and 11 in the presence of sodium hydroxide or into 1,3,4-thiadiazoles 14a-c and 15 in the presence of sulfuric acid. On the other hand, 10c and 11 were also reacted with alkyl halides to obtain their thioether derivatives, 12a,b and 13. All the synthesized compounds were characterized by their elementary analysis and by using UV, IR, NMR and mass spectrometry. 6b, c, f, h-k, m, 7, 7d, 8c, 9, 10c, 11, 12a-b, 13, 14 and 15 were tested for antimicrobial activity, but no significant activity was observed.
Anti-Bacterial Agents↗
Microvascular invasion and survival in cancer of the oral cavity and oropharynx.
Although the presence of squamous cell carcinoma within the peritumoral vascular spaces of primary lesions of the oral cavity and oropharynx has been statistically linked to regional lymph node metastases, the association of this finding with disease control and survival has not been well demonstrated. To evaluate this relationship, we have reviewed the clinical and histopathologic features of 65 consecutive cases of previously untreated T2 or greater squamous cell carcinoma of these sites managed by simultaneous surgical treatment of the primary lesion and regional lymph nodes. Of all the histopathologic features of the primary lesion studied, vascular invasion had the greatest impact on survival, as confirmed by both univariate and multivariate analysis. In addition, vascular invasion correlated statistically with local recurrence, neck recurrence, and distant metastasis.
Adult↗
[Synthesis and cytostatic action of 9-nitronoracronycine].
The synthesis of 9-nitronoracronycine (12) from 1,3-dihydroxy-10-methyl-7-nitroacridone (4) and 2-chlor-2-methyl-3-butyne is reported. Screening tests with the transplantation tumor leukemia P 388 proved 4 and 1-methoxy-10-methyl-7-nitroacridone (14) to be inactive. 12 and 3-methoxy-10-methyl-7-nitroacridone (15) showed cytotoxicity in higher doses. Structure-activity relationships are discussed.
Acronine↗
Long-term improvement in renal function after short-term strict blood pressure control in hypertensive nephrosclerosis.
Seventy-nine hypertensive nephrosclerosis patients entered a prospective randomized single-blind study to 1) establish the pattern of decay of renal function in this population and the variability therein and 2) to determine if strict diastolic blood pressure (DBP) control (less than or equal to 80 mm Hg) is more effective than conventional levels (90-95 mm Hg) in conserving renal function. Because of unexpected significant improvement in renal function in patients from both groups, which changed the perspectives on the course of this disease as described herein, this report is being published before completion of the trial. The selection criteria were 1) serum creatinine concentration of 1.6-7.0 mg/dl, 2) glomerular filtration rate of less than 70 ml/min/1.73 m2, and 3) absence of diseases (other than hypertension) known to destroy renal function. Renal function was assessed by glomerular filtration rate [( 125I]iothalamate clearance) and serum creatinine concentration. Before randomization, DBP was aggressively treated to reduce it to less than 80 mm Hg. Twenty-two subjects (14 in the strict DBP control group and eight in the conventional DBP control group) have been enrolled in the study for 36 months. In contrast to results from previous studies in humans and rats, renal function improved in both patient groups. Thus, irrevocable progression of renal damage after onset of renal failure from high blood pressure does not necessarily occur, and in fact, long-term improvement of renal function resulted from the effects of the study itself.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Verapamil ameliorates acute cyclosporine A (CsA) nephrotoxicity and improves immunosuppression after cadaver renal transplantation.
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Adult↗
Prevention of acute cyclosporine-induced renal blood flow inhibition and improved immunosuppression with verapamil.
Pretreatment with calcium antagonists such as verapamil (VP) and isradipine prevents CsA-induced decrease in renal microcirculation in mice. Recently, in posttransplant cadaver renal transplant (CRT) recipients, we demonstrated a CsA-induced 70% reduction in renal parenchymal diastolic blood flow velocity (PDBFV). Using duplex Doppler scanning, this randomized study of forty CRT patients examines the effect of pretreatment with VP on renal blood flow velocity and posttransplant function. Patients with initially low PDBFV (less than 8.0 cm/sec) who received VP therapy prior to administration of CsA experienced prompt restoration of flow, and continued to improve during CsA administration. With CsA alone, PDBFV diminished from 8.9 +/- 2.4 (SD) to 5.3 +/- 2.7 cm/sec (P less than 0.002). Although blood CsA levels were significantly higher at 1, 4, and 7 days (68, 184, and 235 ng/ml, respectively), after CsA induction, during VP treatment than in control patients (39, 105, and 156 ng/ml, respectively) (P less than 0.001), with the same daily doses of CsA, serum creatinines at day 7 were lower during VP treatment (1.28 +/- 0.44 vs. 1.66 +/- 0.44 mg%) than in controls (P less than 0.01). When the glomerular filtration rate was less than 45 ml/min on day 1. VP-treated patients showed greater improvement in GFR at day 7 by 34.1 +/- 10.9 ml/min compared with the 18 +/- 13 ml/min in controls (P less than 0.02). Only 3 of the 22 VP patients had rejection episodes within 4 weeks, versus 10 of the 18 recipients randomized to no drug (P less than 0.005). We conclude that VP is beneficial in CRT because it improves renal blood flow characteristics and prevents CsA-induced inhibition of blood flow. VP also ameliorates CsA-induced acute nephrotoxicity, and is associated with improved immunosuppression and fewer early rejections.
Cyclosporins↗
Deleterious effects of stroma-free hemoglobin used as resuscitative fluid for rats with ischemic intestinal shock.
This study examined the effect of modified stroma-free Hgb solution (SFHS) as a resuscitative fluid for rats in an ischemic intestinal shock model. The experiments compared the effect of SFHS with two other resuscitative fluids: lactated Ringer's solution (RL) and 3% albumin in RL. The control group received no fluids. After the induction of shock, the resuscitative solution was given iv over a 6-h period. RL and albumin in RL resulted in long-term (greater than 7 days) survival in 15 of 16 animals. All animals in the control group and six of eight animals in the SFHS-treated group died within 24 h. Hct was used to estimate changes in intravascular volume. All control animals became hemoconcentrated and exhibited a 50% loss in plasma volume. The failure of SFHS to improve significantly the survival in rats compared to the controls is surprising in view of the fact that the SFHS had the same oncotic pressure as the albumin-containing solution and identical volumes were administered.
Albumins↗