Phase I and pharmacokinetic study of tiazofurin (TCAR,NSC 286193) administered by continuous infusion

Summary Tiazofurin (2--D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M². Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.Abbreviations TCAR Tiazofurin - HPLC High performance liquid chromatography - IMPD Inosine monophosphate dehydrogenase - WBC white blood cell - CPK creatine phosphokinase - C_ss steady-state concentration     

Assessment of ventricular function by radionuclide angiography in patients receiving 4′-epidoxorubicin and mitoxantrone

Summary Serial assessment of ventricular function by means of radionuclide angiography was performed in 50 patients with malignant neoplasms who received either 4-epidoxorubicin or mitoxantrone for longer than 3 months.In 9 of 30 patients give 4-epidoxorubicin, a decrease of 10% in the left ventricular ejection fraction (LVEF) was documented at doses of 143–1200 mg/m². Two patients developed clinical signs of cardiotoxicity at a dose of >1000 mg/m².In 6 of 20 patients given mitoxantrone a decrease of 10% in the LVEF occurred at doses of 26–98 mg/m².This study was supported in part by a grant from the National Cancer Association of South Africa     

Uptake and clearance rates for kepone in two marine fish species 1

The concentration of kepone (chlordecone) 3 causing 50% mortality of a test population (96 hr LC50) was 17.4 g/L forBrevoortia tyrannus (Atlantic menhaden) and 28.8 g/L forMenidia menidia (Atlantic silverside). In separate experiments, the estimated rate constants for uptake of kepone were 280 and 293/day for menhaden and 102 and 238/day for silversides. The rate constants for clearance were estimated to be 0.03 and 0.13/day for menhaden and 0.002 and 0.01/day for silversides. Based on these rates of uptake and clearance, the equilibrium bioconcentration factor is estimated to lie between 2300 and 9750 for menhaden and 21700 and 60200 for silversides.Contribution No. 1188 from the Virginia Institute of Marine Science, School of Marine Science, Gloucester Point, Virginia 23062     

Reduction suction mammoplasty and suction lipectomy as an adjunct to breast surgery

Suction lipectomy has become an accepted procedure and its full use is still being elucidated. The author herein describes the use of suction lipectomy as an adjunct in refining the results of established surgical procedures on the breast. The authors also explain the use of suction lipectomy in doing suction reduction mammoplasty. The advantages of the use of suction lipectomy as an adjunct to breast surgery and for reduction mammoplasty are explained.     

Controversies in plastic surgery: Suction-assisted lipectomy (SAL) and the hCG (human chorionic gonadotropin) protocol for obesity treatment

The advent of SAL (suction-assisted lipectomy) has dramatically increased the number of obese patients coming to our consultation offices. Despite several articles suggesting a conservative approach to fat suction, some reports insinuate that SAL might be a useful tool for obesity treatment. This hypothesis is refuted by a vast body of evidence that concludes that the adipose tissue may regenerate in adult humans. Therefore, surgical procedures are not advised as the method of choice to manage the disease. On the other hand, the terms obesity and being overweight may not be interchangeable. Obesity may be a disease whereas being overweight is asign of the disease. Consequently, proper preoperative selection of candidates for SAL becomes mandatory. The hCG (human chorionic gonadotropin) method for obesity treatment appears to be a complete program for the management of obesity. It contains pharmacologic, dietetic, and behavior modification aspects in a 40-day course of treatment. Some data suggest hCG to be lipolytic, thus explaining former clinical observations regarding body fat redistribution in treated patients. hCG commercial preparations contain -endorphin, an opioid peptide linked to mood behavior. This article speculates on the possible actions of the complex hCG -endorphin in the neuromodulation of mood and energy metabolism. The method comprises a behavior modification that helps in handling the patient better. There are some correlations between a current behavior modification program and the basic guidelines contained in the hCG protocol. Thus, the hCG method appears to be a reasonable alternative in the management of a long-standing, unsolved problem of human metabolism.     

A COMPARATIVE STUDY IN THE USE OF CLOSED-CIRCUIT TELEVISION READING MACHINES AND OPTICAL AIDS BY PATIENTS WITH RETINITIS PIGMENTOSA AND MACULOPATHY

Patients with retinitis pigmentosa (RP) who have insufficient vision to benefit from optical low vision aids are frequently helped by the closed-circuit television (CCTV) reading machines. RP patients' use of the CCTV is compared with that of patients with maculopathy (i.e. a group with a central scotoma only, is compared to a group which also has additional peripheral field loss), and with that of a "normal" control group. The performance of people with RP is improved by using white print on a black background, while macular degeneration subjects have no significant preference. Speed limits appear to be a function of restrictions imposed by the machine. Both groups frequently read faster with "optical aids".     

Protective role of thiols in carcinogen-induced DNA damage in rat liver

Biological thiols are known to play an important role in thedetoxification of xenobiotics, including chemical carcinogens.To determine the influence of cellular thiols on carcinogeninduction of hepatic DNA damage in the rat, diethylmaleate (DEM)administration was used to deplete intracellular gluta-thione(GSH). The effects of administration of the synthetic thiols,N-acetylcysteine (NAC) and alpha-mercaptopropionyl-glycine (MPG),on the induction of DNA lesions were also examined. Pretreatmentwith DEM reduced liver GSH levels by >70%. As assessed bythe technique of alkaline elution, subsequent administrationof N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) resulted inDNA damage 4 h post MNNG treatment which was 4- to 8-fold greaterthan that induced in the livers of rats treated with MNNG alone.However, DEM pretreatment had little effect on the extent ofDNA damage induced by methylnitrosourea (MNU). DEM alone didnot cause any measurable DNA damage. Pretreatment with MPG orNAC reduced MNNG-induced DNA damage by as much as 77%. In contrast,MNU-induced DNA damage was increased by MPG treatment whereasNAC treatment was without effect. These results indicated thatin the rat liver, the activity of some DNA alkylating agentsmay be modulated in varying degree by the concentration of intracellularthiols. These data support the notion that thiols play an importantrole in protection against carcinogen damage, and that syntheticthiols such as MPG and NAC may be useful as anti-carcinogenicagents against certain carcinogens.     

“Handedness” of spiral fractures of the tibia

Handedness is a basic property of spirals. In many cases it is possible to determine whether spiral fractures are right or left handed by analysis of radiographs. Spiral fractures of the tibia show striking bilateral symmetry, with right-handed spirals predominating on the left side of the body, and left-handed spirals on the right.     

Tackling the frailty burden with an integrative value-based approach: results from a mixed-methods study

Journal of Public Health - The purpose of this paper is to investigate the implementation of value-based care principles in the context of frailty in the perioperative process, highlighting the...