Infected pancreatic fluid collections: percutaneous catheter drainage

Thirty-eight infected pancreatic fluid collections in 23 patients with acute or chronic pancreatitis were drained percutaneously following initial diagnosis with computed tomography and fine-needle aspiration. Fifteen (65.2%) patients were cured completely without surgery. Eight (34.8%) patients required some type of surgery despite successful treatment of the fluid collection, and in two (6.5%) the collection recurred after catheter removal. Complications occurred in three (13%) patients, but only one complication (4%), empyema, was a direct result of catheter drainage. Catheter drainage time averaged 29 days for 16 patients with isolated collections and 96 days and 104 days for patients with collections with pancreatic duct fistulas (nine patients) or gastrointestinal fistulas (14 patients), respectively. This study confirms that infected pancreatic fluid collections can be safely and effectively treated with percutaneous catheter techniques in most patients.     

Pretreatment of Chinese hamster V79 cells with MNU increases survival without affecting DNA repair or mutagenicity

Exposure of Chinese hamster V79 cells to a non-toxic dose ofN-methyl-N-nitrosourea, followed at intervals by exposure totoxic challenging doses of the same agent, resulted in increasedsurvival of colony forming ability when these cells were comparedwith matched control cells that only received the challengingdose. The extent of the increase was dependent on the time intervalbetween exposures, and rose to a maximum of about two-fold 5days after the initial dose, declining slowly to control valueson subsequent days. Whilst pretreatment enhanced survival, italtered neither the frequency of mutation to 6-thioguanine resistance,nor the formation or loss of 3-methyladenine, 7-methylguanineand O⁶-methylguanine. Modification of the conditions by whichthe initial dose was administered led to a reduction or abolitionof the survival response. It is suggested that enhanced survivalmay result from alterations in the ability to recover from cellulardamage rather than by improved DNA repair.     

Effects of carcinogens and partial hepatectomy upon the hepatic O6-methylguanine repair system in mice

The enhanced repair of O⁶-methylguanine from hepatic DNA inrats is a well established phenomenon that can be induced bypretreatment with a variety of hepatotoxic agents as well asby partial hepatectomy. Attempts to induce a similar hepaticresponse by treatment with single doses of aflatoxin B₁ in C57Blmice, single doses of dimethylnitrosamine (DMN) in C57BI orBALB/C mice or by prolonged pretreatment with DMN by additionto the drinking water of C57Bl mice were uniformly unsuccessful.Furthermore, the intense proliferative response induced by two-thirdspartial hepatectomy in C57Bl mice was also apparently incapableof increasing the activity of this repair function. These experiments,in which repair of O⁶-methylguanine has been determined bothin vivo after administration of [¹⁴C]DMN and in vitro usingcrude tissue extracts and a methylated DNA substrate, indicatethe presence of an intergeneric difference between rats andmice with respect to this repair function.     

Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamsters and the persistence of alkylated purines in the DNA of various tissues

The carcinogenicity of N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) has been determined in adult male Syrian golden hamsters following a single i.p. injection or two-thirds of the acute 50% lethal dose, or 30 and 60 mg/kg, respectively. The principal site of action of these agents was the forestomach, squamous cell papillomas of this organ developing in 53 and 61% of the animals receiving the higher doses of NMU and N-nitroso-N-ethylurea, respectively. NMU also induced a low incidence of liver tumors (17%). Very few tumors were seen at other sites. The formation and removal of alkylated purines in DNA was measured in various tissues up to 50 hr after administration of [14C]NMU. Methylation products were detected in all tissues examined, the level in liver being somewhat higher than in other tissues. The removal of 7-methylguanine and 3-methyladenine from DNA occurred at approximately similar rates in all tissues examined, indicating no substantial differences in N-glycosylase activities. Removal of the promutagenic DNA lesion O6-methylguanine varied considerably from tissue to tissue; very little occurred in brain or kidney, while up to 36 and 32% were lost from DNA of intestine and testes, respectively. In the liver, there were relatively small changes in O6-methylguanine levels up to 24 hr; but by 50 hr, 38% had been removed. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of the brain and intestine and lowest in that of the liver. These results indicate that in this experimental system, the formation and persistence of O6-methylguanine in DNA is insufficient alone to account for the organotropic effect of NMU.     

Transfection of murine multi-potent haemopoietic stem cells with an E.coli DNA alkyltransferase gene confers resistance to the toxic effects of alkylating agents

O⁶-alkylguanine-DNA-alkyltransferase (ATase)-deficient murinehaemopoietic stem cells were transfected, following electroporation,with a G418-selectable expression vector containing the proteincoding region of the Escherichia coli ATase gene ada. Clonesof cells that were resistant to G418 or the chloroethylatingagent mitozolomide (Mz) were selected and most were shown toexpress very high levels of bacterial gene-encoded ATase. Incomparison with control cells that were transfected with theparent vector, the ATase-expressing clones were considerablymore resistant to the toxic effects of the methylating agentsN-methyl-N-nitrosourea and methylmethanesulphonate or the chloroethylalingagents Mz or taurine chloroethylnitrosourea, but unchanged intheir susceptibility to the bis-chloroethylating agent nitrogenmustard. Thus alkylatlon damage in DNA that can be repairedby the E.coli ATase constitutes the principal lethal lesionproduced by alkylating agents in murine haemopoietic stem cellsand the ATase deficiency in these cells can be complementedby electroporation-mediated gene transfection.     

Urinary melatonin excretion throughout the ovarian cycle in menstrually related migraine

Nocturnal urinary melatonin excretion was significantly decreased throughout an ovarian cycle in 12 migraine without aura patients compared to 8 healthy controls. Normal increases in urinary melatonin excretion during the luteal phase was less pronounced in the migraine patients. Melatonin excretion was further decreased during headache. The data indicate impaired pineal function in migraine.     

Effect of chronic administration of dimethylnitrosamine on the excision of 0-methylguanine from rat liver DNA

Rats were exposed chronically to unlabelled N,N-dimethylnitrosamine (25 ppm in the drinking water) then given a single dose of N-[³H]methyl-N-nitrosourea (10 mg/kg body weight). The rates of loss of tritium-labeled 7-methylguanine, 0⁶-methylguanine and 3-methyladenine from the liver DNA in control and dimethylnitrosamine-treated rats were found not to be significantly different. Thus, under the conditions used, inhibition of the 0⁶-methylguanine excision repair system does not seem to be a factor in the induction of liver tumours by chronic DMN application.