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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 127 records · Page 7Linked to original sources
PubMed1993

A tobacco-specific lung carcinogen in the urine of men exposed to cigarette smoke.

BACKGROUND: Environmental tobacco smoke has been classified by the Environmental Protection Agency as a carcinogen causally associated with lung cancer in adults, but there have been no reports of lung carcinogens or their metabolites in the body fluids or tissues of nonsmokers exposed to environmental tobacco smoke. METHODS: Five male nonsmokers were exposed to sidestream cigarette smoke generated by machine smoking of reference cigarettes for 180 minutes on each of two days, six months apart. Sidestream smoke is the smoke that originates from the smoldering end of a cigarette between puffs. Twenty-four-hour urine samples were collected before and after exposure. The urine samples were analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide, which are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in rodents. NNAL is also a lung carcinogen in rodents. RESULTS: The urinary excretion of the metabolites increased after exposure to sidestream smoke in all the men. The mean (+/- SD) amount of NNAL and NNAL glucuronide was significantly higher after exposure than at base line (33.9 +/- 20.0 vs. 8.4 +/- 11.2 ng per 24 hours [127 +/- 74 vs. 31 +/- 41 pmol per day], P < 0.001) and was correlated with urinary cotinine excretion (r = 0.89, P < 0.001). The nicotine concentrations in the air to which the men were exposed were comparable to those in a heavily smoke-polluted bar. CONCLUSIONS: Nonsmokers exposed to sidestream cigarette smoke take up and metabolize a lung carcinogen, which provides experimental support for the proposal that environmental tobacco smoke can cause lung cancer.

Adult↗
PubMed1993

A study of tobacco carcinogenesis. LI. Relative potencies of tobacco-specific N-nitrosamines as inducers of lung tumours in A/J mice.

Tobacco-specific N-nitrosamines (TSNA) are formed from nicotine and the minor Nicotiana tabacum alkaloids during tobacco processing and tobacco smoking. The TSNA are the most abundant strong carcinogens in smokeless tobacco and in smoke. In this comparative study six TSNA and two major volatile N-nitrosamines of cigarette smoke are assayed for their relative tumorigenicities in strain A/J female mice and for their potential to induce lung tumors. N-nitrosodimethylamine was the most potent inducer of lung adenoma in the A/J mouse model followed in order of decreasing potencies by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N-nitrosopyrrolidine, N'-nitrosonornicotine and N'-nitrosoanabasine. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol and 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid were inactive. The relative tumorigenic activities of the tobacco-specific nitrosamines in strain A/J mice compare well with the available data for their relative tumorigenic activities in F344 rats and Syrian golden hamsters.

Adenoma↗
PubMed1993

A study of tobacco carcinogenesis: effect of the fat content of the diet on the carcinogenic activity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in F344 rats.

3 Epidemiological studies indicate that the risk of cigarette smokers for cancer of the lung and of the pancreas is influenced by the fat content of the daily diet. In a long-term bioassay (24 months), we gave F344 rats 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific and strongly carcinogenic N-nitrosamine, as a 2 ppm solution in the drinking water. One group of rats was given a high-corn oil diet (23.5%), and the second group received a low-corn oil diet (5.0%). The animals on the high-corn oil diet and NNK (NNK-HF), and the control animals on the same diet but on tap water (HF) had significantly higher body weights and shorter life spans than the rats on a low-corn oil diet and NNK (NNK-LF) and the corresponding control rats receiving the low-corn oil diet and tap water (LF). Eighteen months into the bioassay, 16 of 60 rats in the NNK-HF group had developed lung tumors averaging 6.8 mm2, while 3 of 60 rats in the NNK-LF group had tumors averaging 2.5 mm2. At the termination of the experiment after 24 months, the numbers of rats with lung tumors in the NNK-HF and NNK-LF groups did not significantly differ from each other, nor was there a difference in the size of the lung tumors. The effect of dietary fat on the pancreas tumor incidence was more pronounced. After 18 months, 11 of 60 rats treated with NNK-HF but only one of 60 rats treated with NNK-LF had developed pancreas tumors. At the termination of the study, 28 NNK-HF-treated rats had pancreas tumors (17.5 +/- 13.5 mm) compared to 19 NNK-LF-treated rats (9.6 +/- 11.7 mm2). After 24 months 6 of 20 rats in each of the control groups (HF and LF) had developed pancreas tumors. In fact, there was an increasing trend of development of pancreas tumors in these control rats with aging regardless of dietary fat variance. However, in view of the observed tumor acceleration and enhancement this study points to the importance of evaluating both exposure to tobacco carcinogens and dietary fat intake as risk factors for tobacco users.

Adenoma, Islet Cell↗
PubMed1993

Potential inhibitors of tobacco carcinogenesis.

Tobacco smoking is causally associated with cancer of the lung, upper aerodigestive tract, pancreas, renal pelvis and urinary bladder. Tobacco chewers and especially snuff dippers face an increased risk for cancer of the oral cavity and pharynx. Although cessation of the tobacco habits is the only sure way to avoid an increased risk of tobacco-related cancers, certain modified products should be available to lower the incidence rates for cancer among those tobacco chewers and smokers who are unable to give up their tobacco habits. The modified cigarette has been the first approach toward the reduction of cancer risk. In the case of cancer of the lung, the long-term smoker of low-yield filter cigarettes has a risk reduction of 30-50% over that of the smoker of nonfilter cigarettes; however, the risk of filter cigarette smokers for cancer of the lung and cancer at other sites is still many times higher than that of the nonsmoker. A second modality is the application of natural or synthetic chemopreventive agents. Clinical studies with tobacco users have been primarily limited to the application of beta-carotene and retinoids. Although the data appear encouraging in respect to reducing early lesions in the oral cavity of tobacco chewers and smokers and in respect to second primaries in smokers, the benefits of beta-carotene and retinoids are gradually reversed upon withholding these micronutrients. It is understandable that activities in respect to chemopreventive agents in clinical trials on smokers are limited, since cessation of smoking alone leads within only a few years to a significant reduction of the cancer risk. Another reason for the limited interest in clinical trials on smokers may relate to the lack of laboratory data on the actual effects of chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents have been tested in mice and rats which were treated with carcinogenic, tobacco-specific N-nitrosamines (TSNA). The results appear most encouraging in respect to lung tumor reduction. It is hoped that this type of research will gain in interest. Human data suggest that the fat content of the diet influences the cancer risk of smokers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Synthesis and antitumor activity of isodoxorubicin analogues.

The synthesis and biological activity of the new 4-demethoxyanthracyclines 15, 22, and 23 are reported. They were obtained from synthetic 9-deacetyl-9-(hydroxymethyl)-4-demethoxydaunomycinone (isopropylidene derivative 9) and from 4-azido- or 4-amino-2,4,6-trideoxy-L- lyxo-hexoses. Anthracycline 22 (hydrochloride salt), the most active compound in the series, was slightly more potent than doxorubicin in vitro against three cell lines (L1210, HT29, A549). It was found to exhibit similar antitumor activity in vivo (iv route) against L1210 leukemia, but was less active than doxorubicin against three human tumors in a subrenal capsule assay LXF, A549, and HT29).

Animals↗
PubMed1993

[Stimulators of the central nervous system].

Progress in biomedical engineering has provided implantable and programmable stimulators which allowed application of neurophysiological knowledge to therapeutic attempts on human neurological diseases. Chronic electrodes can be implanted accurately and safely into the brain, against the spinal cord and around the nerves. Therapeutic applications, mainly on pain, dyskinesias and epilepsy are therefore available, which call for careful clinical evaluation, basic and technological research to improve indications and diminish the cost of these methods.

Central Nervous System↗
PubMed1993

[Long-term treatment of mucoviscidosis. Results with a microencapsulated pancreatic enzyme preparation].

METHODS: In 30 children suffering from cystic fibrosis, the long-term effect (2 years) of treatment with an acid-protected micro-encapsulated pancreatin preparation was investigated in comparison with prior enzyme replacement with a conventional pancreatin preparation given over a period of years. Assessment criteria was the development of body length and body weight, lung function (vital capacity, FEF1) and the Shwachman-Kulczycki score. RESULTS: The therapeutic efficacy of the acid-protected micro-encapsulated preparation is considered to be higher than that of conventional preparations, since the same effect was achieved with only one-quarter to one-third of the pancreatin dose of the conventional preparation (average: 6.5 +/- 2.9 g pancreatin/d, as compared with 1.6 +/- 0.6 g pancreatin in the case of the acid-protected micro-encapsulated preparation). However, none of the clinical parameters investigated revealed any significant changes during the course of the observation period. The results indicate that, if the general state of health and nutritional status of patients with cystic fibrosis is to be improved further, in addition to a special diet, attempts must be made to achieve further optimization of the intraluminal digestion.

Adolescent↗
PubMed1993

Intracerebral low frequency electrical stimulation: a new tool for the definition of the "epileptogenic area"?

Low Frequency (1 Hz) Electrical Stimulation (LFES) has been systematically utilized, during stereo-EEG investigations, in 24 consecutive young adult patients considered for surgical treatment of severe drug-resistant partial epilepsy. Ninety seizures (1-14/patient) identical to the spontaneous ones previously recorded were thus obtained in 19 patients (79%). LFES is less effective for induction of seizures than high frequency (50 Hz) stimulation (5.9% vs 22.9%), and it also provokes less "false positive" responses (1% vs 17%). The main "sensitive" structures to LFES are the hippocampus, the amygdala, and the hippocampal gyrus. However, seizures were also induced by stimulating the temporal lobe white matter, the temporal pole, and the temporal neocortex, as well as the orbito-frontal cortex (in the only patient with fronto-temporal epilepsy). The more frequently observed electrical pattern is a gradual increase of spikes and spikes and waves frequency, with or without occurrence of low voltage fast activity. The high percentage of early "subjective" manifestations similar to the spontaneous ones, the lack of major electrical artifact, and the good visualization of the spatial evolution of the induced-discharge, strongly suggest that LFES is of great help for defining the "epileptogenic area".

Adult↗
PubMed1993

Chronic VIM thalamic stimulation in Parkinson's disease, essential tremor and extra-pyramidal dyskinesias.

Stereotactic thalamotomy of the VIM (ventral intermediate) nucleus is considered as the best neurosurgical treatment for Parkinsonian and essential tremors. However, this surgery, especially when bilateral, still presents a risk of recurrence and neurological complications. We observed that acute VIM stimulation at frequencies higher than 60 Hz during the mapping phase of the target suppressed the tremor of Parkinson's disease (PD) and essential tremor (ET). This effect was immediately reversible at the end of the stimulation. This was initially proposed as an additional treatment for patients already thalamotomized on the contralateral side, and then extended as a regular procedure for extra-pyramidal dyskinesias. Since January 1987, we implanted 126 thalami in 87 patients (61 PD, 13 ET, 13 dyskinesias of various origins). Deep brain stimulation electrodes were stereotactically implanted under local anaesthesia, using stimulation and micro-recording to delineate the best site of stimulation. Electrodes were subsequently connected to implantable programmable stimulators. The optimal frequency was around 130 to 185 Hz. The results (evaluated by a neurologist from 0 = no effect to 4 = perfect relief) are related to the type of tremor. Altogether, 71% of the 80 patients benefited from the procedure with grade 3 and 4 results. In 88% of the PD cases, the results were good (grade 3) or excellent (grade 4) and stable with time. Rigidity was moderately for a long improved but akinesia was not. The same level of improvement was observed in 68% of the ET patients and only in 18% of the other types of dyskinesias.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia Diseases↗
PubMed1993

The need for regulation of carcinogenic N-nitrosamines in oral snuff.

Oral snuff is carcinogenic to humans and laboratory animals. The major carcinogenic agents in snuff are the N-nitrosamines, especially the tobacco-specific N-nitrosamines. During the past decade, a gradual reduction of the levels of carcinogenic N-nitrosamines was observed in the leading snuff brands in the USA and in Sweden. However, in 1990 a newly introduced snuff brand in the USA contained the highest concentration of carcinogenic N-nitrosamines ever to be determined in a commercial tobacco product. The elevated pH and relatively high levels of nitrite in this snuff favoured the formation of N-nitrosamines. 2 yr after the product first appeared, it was replaced by a new preparation of snuff under the same brand name, and, according to chemical analyses, this material would be expected to have about the same carcinogenic potential as the leading snuff products. The interdependence of the formulation and manner of preparation of snuff products with their carcinogenic potential emphasizes the need for regulation and control of the harmful substances in smokeless tobacco, especially in view of the trend of increasing consumption of snuff.

Carcinogens↗
PubMed1993

[Electroclinical manifestations elicited by intracerebral electric stimulation "shocks" in temporal lobe epilepsy].

In patients with severe drug-resistant partial epilepsy, undergoing Stereo-EEG investigations, spatial definition of the "epileptogenic area" is mainly based on spontaneous seizures recordings, but also on seizures induced by intracerebral electrical stimulation (ES). Only "trains" ES (TES, 50 pps) are currently used with this aim; "shocks" ES (SES, 1 pps) are principally applied to localize motor pathways. We have shown, during a prospective study concerning 10 temporal lobe epileptic patients, that SES could frequently induce seizures, especially when stimulation is applied in the anterior part of the Ammon's horn. Even if its efficacy seems lower than by TES, this kind of stimulation, in the majority of the cases, does reproduce isolated ictal subjective symptomatology, allowing the visualization of the progressive organisation of ictal electrical discharges, and avoids "unexpected" ("false positive"?) clinical responses.

Adolescent↗
PubMed1993

Clinical pathology of Australian bluetongue virus serotype 16 infection in merino sheep.

Viraemic blood from an ox naturally infected with Australian bluetongue (BLU) virus serotype 16 was passaged twice in sheep. Twelve 2- to 4-years-old Merino ewes, negative in a bluetongue agar gel immunodiffusion test, were inoculated with viraemic blood from the second sheep passage. They were examined for 18 days and compared with a control group. Significant changes in haematological measurements, namely packed cell volume, total white cell count and lymphocyte count, and in plasma enzyme concentrations, namely aspartate transaminase and creatine kinase, occurred in the infected sheep. All infected sheep became sick. The antibody response, and clinical and necropsy findings were consistent with other reports of mild to moderate disease with Australian BLU serotypes.

Animals↗
PubMed1993

[Effects of the stimulation of the subthalamic nucleus in Parkinson disease].

In Parkinson's disease, experimental studies favour a neuronal hyperactivity of the subthalamic nucleus. We carried out a subthalamic nucleus electrical stimulation in a patient aged 51, suffering for 8 years from a severe akineto-rigid form of Parkinson's disease, complicated with an on-off effect. Stereotaxic surgery was done under local anaesthesia on one side. Within the theoretical target, a 130 Hz stimulation induced akinesia alleviation mainly on the contralateral limbs. No abnormal movement was noticed. Then a long-term quadripolar DBS Medtronic electrode was inserted in that area. The study of the effects of chronic stimulation is in progress to determine the best temporal and electrical stimulation variables.

Electric Stimulation Therapy↗