Informed consent. Research suffers if patients suspect that their rights may be breached.
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Attitude↗
Biomedical subjects
B Toth
Publications and source records attributed to B Toth.
Subacute uremic and diabetic polyneuropathy.
We present 4 patients who had a subacute, predominantly motor polyneuropathy associated with diabetes mellitus and end-stage renal disease. Electrophysiological studies and muscle biopsy indicated a primary axonal degeneration of nerve with secondary segmental demyelination, and mild to moderate, acute and chronic denervation of muscle. A relative absence of denervation potentials on needle electromyography was an unusual feature. Three of our patients improved with a switch from conventional to high-flux hemodialysis. We speculate on possible mechanisms.
Aged↗
Outbreak of sporotrichosis among tree nursery workers.
In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was conducted to identify risk factors for sporotrichosis, and an environmental investigation was done. The risk of sporotrichosis increased significantly with the duration of working with sphagnum moss (P < .05), in particular with filling topiaries (P < .05), and with having less gardening experience (P < .05). Wearing gloves was protective (P < .005). Sporothrix schenckii was cultured from patients and sphagnum moss used in topiary production. Use of restriction fragment length polymorphism revealed an identical pattern for patient isolates that was different from the patterns of environmental isolates. Physicians should be aware of sporotrichosis in patients with ulcerative skin lesions who have a history of occupational or recreational exposure to sphagnum moss.
Adult↗
8-Arylguanine adducts from arenediazonium ions and DNA.
Arenediazonium ions (ArN2+) are genotoxic though the source of their genotoxicity is unknown. The present studies were undertaken to determine if reductive decomposition of ArN2+ to aryl radicals (Ar) in the presence of calf thymus DNA (ctDNA) or in cells results in the formation of DNA adducts. We found that when arenediazonium ions of the general structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH) are allowed to react with ctDNA or incubated with cells under conditions that produce p-X-Ar, DNA adducts are formed with guanine. The structure of the adduct is the C8-substitution product derived from guanine and p-X-Ar. Formation of p-X-Ar was determined by ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The extent of C8-arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with authentic synthetic standards. The C8-arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN2+, though other DNA adducts such as the N6-triazene of adenine or C8-aryladenine adducts can form. Finally, though the formation of C8-arylguanine adducts from arenediazonium ions has been proposed, this is the first report demonstrating their formation in DNA.
Animals↗
Is research into the treatment of osteoarthritis with non-steroidal anti-inflammatory drugs misdirected?
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Anti-Inflammatory Agents, Non-Steroidal↗
Agaricus bisporus: an assessment of its carcinogenic potency.
This assessment focuses on the concentrations of some chemicals present in the Agaricus bisporus mushroom, the cancer-inducing doses of these chemicals or mushroom used in the animal experiments, the total amounts of these chemicals or mushroom needed to induce cancer in these mice, and the estimated total amounts of these chemicals or mushroom needed to induce cancer in humans. By adding the estimated amounts of chemicals needed to induce cancer and by comparing it with the amount of raw mushroom needed to induce the same effect, it becomes obvious that we have accounted for less than 2% of the carcinogenic components of the Agaricus bisporus mushroom. Since some unavailable data handicapped this assessment, it should be regarded as tentative and subject to further adjustment.
Agaricus↗
Randomized clinical trials for retrolental fibroplasia.
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Humans↗
A clinical evaluation of a blood conservation device in medical intensive care unit patients.
OBJECTIVES: This study was designed to a) document the efficacy of a device intended to conserve blood in critically ill patients; b) determine the effect of this blood conservation on hemoglobin concentration and the need for blood transfusions; c) determine if the blood conservation device resulted in interference with arterial pressure waveforms; d) determine if use of the blood conservation device resulted in a difference in the number of accidental needle punctures suffered by healthcare workers. DESIGN: Prospective, randomized, controlled trial. A clinical trial using prospective, random allocation of consecutive eligible patients. SETTING: The medical intensive care unit (ICU) of a university hospital located in a large metropolitan area. PATIENTS: A total of 100 patients who were admitted to the medical ICU, required arterial line monitoring for clinical purposes, and were managed by the ICU medical service. Exclusion criteria included active bleeding or chronic renal failure at the time of ICU admission. INTERVENTIONS: Patients in the experimental group had a blood conservation device incorporated into the arterial pressure monitoring system, while patients in the control group received a conventional arterial pressure monitoring system. MEASUREMENTS AND MAIN RESULTS: Data gathered included: age; gender; ICU discharge status; the duration of ICU stay; time in the study; volume of all blood drawn, discarded, or lost due to leakage; hemoglobin concentrations; blood transfusions; and accidental needle injuries. Arterial pressure waveforms were recorded and inspected for dampening or other deformation. Mean hemoglobin concentrations were compared on ICU admission and at 12-hr intervals. Demographic and clinical characteristics of the two groups were not significantly different. The volume of blood drawn and discarded from arterial catheters was significantly lower in the blood conservation group (blood conservation device: 5.7 +/- 7.5 mL; control: 96.4 +/- 88.5 mL; p < .0001), as was the total volume of blood discarded (blood conservation device: 19.4 +/- 47.4 mL; control: 103.5 +/- 99.9 mL; p < .0001). Mean hemoglobin concentration on admission was similar in the two groups (blood conservation device group: 11.8 +/- 2.5 g/dL; control group: 12.6 +/- 2.3 g/dL). In both groups, the mean hemoglobin concentration declined most rapidly in the first 24 hrs of ICU care and, thereafter, declined more slowly. Although the mean hemoglobin concentration was higher in the blood conservation group after 6 days, statistical significance was not reached until 9.5 days of ICU care. The mean change in hemoglobin concentration (overall: 1.2 +/- 2.2 g/dL) during the study represents a statistically significant (p < .0001) decrease of 9.7%. Hemoglobin concentration during the study decreased by 1.4 +/- 2.2 g/dL in the control group and 1.0 +/- 2.3 g/dL in the blood conservation group (p = nonsignificant). Univariate and multiple regression analysis demonstrated discarded blood volume to be a significant and independent predictor of the decline in hemoglobin concentration. Transfusion requirements were similar in both groups. The blood conservation system did not alter or interfere with pressure waveforms. There were no accidental needle injuries noted. CONCLUSIONS: The conservation of blood in critically ill patients must be a high-priority concern of all healthcare workers. Our data indicate that the blood conservation system eliminates a significant factor in the decline in hemoglobin concentration. With devices as described here, there is no reason to continue the practice of wasting the blood of critically ill patients in order to prevent preanalytic error.
Adult↗
Cancer induction in mice by feeding the raw false morel mushroom Gyromitra esculenta.
One of the false morel mushrooms, Gyromitra esculenta, was administered p.o. to Swiss mice that were 6 weeks old at the beginning of the experiment. The mushrooms were fed to the mice for 3 days and were followed by a semisynthetic diet for 4 days each week for life. The treatment induced tumors in the lungs, nasal cavity, blood vessels, forestomach, glandular stomach, cecum, and liver in the following incidences: 80, 10, 50, 16, 4, 28, and 6% in females, and 70, 12, 32, 18, 20, 22, and 12% in males. In the untreated controls, the corresponding tumor incidences were 28, 0, 14, 0, 0, 8, and 0% in females and 38, 0, 6, 0, 0, 8, and 2% in males. The light microscopic examination revealed the typical appearance of adenomas and adenocarcinomas of lungs, adenomas and adenocarcinomas of nasal cavities, hemangiomas and hemangiosarcomas of blood vessels, squamous cell papillomas and carcinomas of the forestomach, adenomas and adenocarcinomas of the glandular stomach, polypoid adenomas and adenocarcinomas of the cecum, and hepatomas. The work demonstrates the carcinogenic action of the raw G. esculenta mushroom.
Animals↗
Poisoning by Gyromitra esculenta--a review.
Gyromitra esculenta (Pers.: Fr.) Fr. and a few other mushrooms have caused severe poisonings and even deaths in humans. Clinical data are characterized primarily by vomiting and diarrhoea, followed by jaundice, convulsions and coma. Gastrointestinal disorders distinguish this poisoning. Frequent consumption can cause hepatitis and neurological diseases. The species of concern are mainly G. esculenta and G. gigas (Kromb.) Cooke (non Phill.). Nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other Ascomycetes species also may prove toxic. Gyromitrin (acetaldehyde methylformylhydrazone, G) and its homologues are toxic compounds that convert in vivo into N-methyl-N-formylhydrazine (MFH), and then into N-methylhydrazine (MH). The toxicity of these chemicals, which are chiefly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments using animals, cell cultures and biochemical systems. When we consider the chemical nature and the reactivity of these natural compounds, we suggest that chemical and biochemical mechanisms may explain their intrinsic biological activity.
Animals↗
Tumor induction with hexanal methylformylhydrazone of Gyromitra esculenta.
Hexanal methylformylhydrazone (HMFH) was administered to Swiss mice by intragastric instillations at weekly intervals of 52 times at 50 or 100 micrograms/g body weight. The treatment induced tumors of the lungs, liver and preputial glands. The tumor incidences in the group that received the lower dose were 74, 4 and 0% in females and 78, 8 and 6% in the males. In the group with the higher dose, the incidences were 90, 28 and 0% in females and 70, 6 and 86% in males. The corresponding tumor incidences in the untreated animals were 26, 0 and 0% in females and 26, 0 and 0% in males. The histopathological examination revealed adenomas and adenocarcinomas of lungs, benign hepatomas and liver cell carcinomas, and squamous cell papillomas and carcinomas and adenomas of preputial glands. HMFH is the sixth carcinogenic ingredient found in one of the false morel mushrooms, Gyromitra esculenta. Because this fungus is considered edible, the health hazard implications cannot be discounted.
Adenocarcinoma↗
8-Hydroxy-2'-deoxyguanosine formation during the catalytic oxidation of hydrazines in the presence of 2'-deoxyguanosine.
The reaction of 2'-deoxyguanosine (1), substituted hydrazines (Hy) and oxygen, in the presence of Cu(II) as catalyst, yields 8-hydroxy-2'-deoxyguanosine (2). The rate of formation of 2 was found to be dependent upon the oxidation potential of the Hy and on structural factors of the Hy. The conversion of 1 to 2 under these conditions suggested that a Haber-Weiss/Fenton type of process was involved with Hy acting as reductant. However, the dependence of the rate of the conversion of 1 to 2 upon the structure of Hy suggested that the Hy substrates studied may be more directly involved in the process than that of a reducing agent. Additional studies of this reaction system, including the oxygen consumption, radical trapping studies and direct ESR measurements suggest that the conversion of 1 to 2, under the conditions used, involves the intermediacy of complex composed of the metal catalyst, 1, Hy and oxygen. The rate data for the conversion of 1 to 2 appear to be correlated with the carcinogenicity of Hy and therefore 2 may be an important DNA adduct in the carcinogenesis of hydrazines.
8-Hydroxy-2'-Deoxyguanosine↗
Chemical oxidation and metabolism of N-methyl-N-formylhydrazine. Evidence for diazenium and radical intermediates.
N-Methyl N-formlhydrazine (1), a component of the mushroom Gyromitra esculenta, is a carcinogen. Its mode of action, however, is poorly understood. To determine the intermediates that may form during the metabolism of 1, we examined its oxidative chemistry, identified the products and inferred the intermediates on the basis of these products. The incubation of 1 with rat liver microsomes was also studied and the metabolites determined and quantified. Both the chemical and the microsome-mediated oxidation of 1 yielded formaldehyde and acetaldehyde. The formation of acetaldehyde requires (i) the oxidation of 1 to a diazenium ion (I) or diazene (II) and (ii) fragmentation of I/II to formyl and methyl radicals. It is suggested that these radical intermediates may be important in understanding and elucidating carcinogenesis by 1.
Acetaldehyde↗
Laryngeal lipoma.
We present a rare case of an intrinsic lipoma of the left false vocal cord in a 62-year-old man. The tumor was a manifestation of generalized lipomatosis. Successful endolaryngeal removal was accomplished.
Barium Sulfate↗
Oral administration of vanadate to streptozotocin-diabetic rats restores the glucose-induced activation of liver glycogen synthase.
Isolated hepatocytes from streptozotocin-diabetic rats failed to respond to a glucose load with an activation of glycogen synthase. This lesion was associated with severely decreased activities of glycogen-synthase phosphatase and of glucokinase. All these defects were abolished after consumption for 13-18 days of drinking water containing Na3VO4 (0.7 mg/ml), and they were partially restored after 3.5 days, when the blood glucose concentration was already normalized. In all conditions the maximal extent of activation of glycogen synthase in cells closely parallelled the activity of glycogen-synthase phosphatase.
Animals↗
Short-term hormonal control of protein phosphatases involved in hepatic glycogen metabolism.
The prominent protein phosphatases involved in liver glycogen metabolism are the AMD (ATP, Mg-dependent, type-1) and PCS (polycation-stimulated, type-2A) phosphatases. The glycogen synthase phosphatase activity, measured from the rate of activation of liver glycogen synthase, is virtually accounted for by AMD phosphatases; the bulk of the activity belongs to the glycogen-bound protein phosphatase G and a small part is present in the cytosol. The major part of the phosphorylase phosphatase activity present in the post-mitochondrial supernatant is shared by protein phosphatase G and cytosolic enzymes, and a minor part belongs to a microsomal AMD phosphatase. In the liver cytosol, the phosphorylase phosphatase activity is about equally distributed between AMD and PCS phosphatases. Studies in vivo as well as on isolated, perfused livers have shown that glucagon (which raises the level of cyclic AMP) as well as vasopressin (which increases the cytosolic Ca2+ concentration) decrease the phosphorylase phosphatase activity in liver extract or cytosol (filtered through Sephadex G-25) by about 25% within a few minutes. These effects were not additive, and the activity of glycogen synthase phosphatase was not affected. Conversely, insulin as well as glucose increased both phosphatase activities by about 25%, and these effects were additive. Vanadate mimicked the effect of insulin on the perfused liver. All the activity changes were only observed when the assays were performed at high tissue concentration. Upon subcellular fractionation all the effects were well expressed in the cytosol, but not in the particulate fraction (glycogen and microsomes). However, quantitatively the hormonal responses were largely lost during the fractionation procedure; they could be restored by recombination of the liver cytosol from a hormone-treated rat with the particulate fraction from either a treated or an untreated animal. It appears that the effects of glucagon, insulin and glucose are mediated by cytosolic, transferable effectors of the Vmax of protein phosphatases. These effectors are eluted in the void volume of a Sephadex G-25 column. Rats of the gsd/gsd strain, which have a genetic deficiency of hepatic phosphorylase kinase, responded to an injection of insulin plus glucose with a normal increase in the cytosolic phosphorylase phosphatase activity. In contrast, they failed to respond to glucagon as well as vasopressin. A transient 80% inhibition of the phosphorylase phosphatase activity could be induced in vitro in a concentrate liver cytosol from Wistar rats upon addition of MgATP.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Decreased activity and impaired hormonal control of protein phosphatases in rat livers with a deficiency of phosphorylase kinase.
1. Livers from gsd/gsd rats, which do not express phosphorylase kinase activity, also contain much less particulate type-1 protein phosphatases. In comparison with normal Wistar rats, the glycogen/microsomal fraction contained 75% less glycogen-synthase phosphatase and 60% less phosphorylase phosphatase activity. This was largely due to a lower amount of the type-1 catalytic subunit in the particulate fraction. In the cytosol, the synthase phosphatase activity was also 50% lower, but the phosphorylase phosphatase activity was equal. 2. Both Wistar rats and gsd/gsd rats responded to an intravenous injection of insulin plus glucose with an acute increase (by 30-40%) in the phosphorylase phosphatase activity in the liver cytosol. In contrast, administration of glucagon or vasopressin provoked a rapid fall (by about 25%) in the cytosolic phosphorylase phosphatase activity in Wistar rats, but no change occurred in gsd/gsd rats. 3. Phosphorylase kinase was partially purified from liver and subsequently activated. Addition of a physiological amount of the activated enzyme to a liver cytosol from Wistar rats decreased the V of the phosphorylase phosphatase reaction by half, whereas the non-activated kinase had no effect. The kinase preparations did not change the activity of glycogen-synthase phosphatase, which does not respond to glucagon or vasopressin. Furthermore, the phosphorylase phosphatase activity was not affected by addition of physiological concentrations of homogeneous phosphorylase kinase from skeletal muscle (activated or non-activated). 4. It appears therefore that phosphorylase kinase plays an essential role in the transduction of the effect of glucagon and vasopressin to phosphorylase phosphatase. However, this inhibitory effect either is specific for the hepatic phosphorylase kinase, or is mediated by an unidentified protein that is a specific substrate of phosphorylase kinase.
Animals↗