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Biomedical subjects

P Hoffman

Publications and source records attributed to P Hoffman.

At least 73 records · Page 4Linked to original sources

Reflex changes in post- and preganglionic sympathetic adrenal nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat.

The aim of the study was to compare pre- (pre-aSNA) and postganglionic adrenal sympathetic nerve activity (post-aSNA) and postganglionic renal sympathetic nerve activity (rSNA) in rats during arterial baroreceptor activation and haemorrhage. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for pre-aSNA or post-aSNA in adrenal nerves, a ganglionic blocker, trimethaphan (10 mg kg-1), was administered i.v. If the nerve activity in the adrenal nerve decreased or increased the nerve was considered to contain predominantly post- or preganglionic fibres, respectively. In contrast, the renal nerves exhibit an almost pure postganglionic activity. Baroreceptor activity was tested by activation of baroreceptors, with an alpha-receptor agonist, phenylephrine, which was slowly infused (0.5-2 micrograms kg-1 min-1), and to deactivate the baroreceptors the rats were bled down to 50 mmHg for 8 min. The experiments showed that all tested nerve types were baroreceptor dependent. There were no significant differences between the slopes relating nerve activity inhibition to increase in blood pressure (infusion of phenylephrine). During maximal inhibition there was a difference between the rSNA and pre-aSNA, 87 +/- 4%, n = 6, and 68 +/- 6%, n = 10 (P less than 0.01) of the control value, respectively. The maximal inhibition of post-aSNA was 80 +/- 3%, n = 7, of the control value. During haemorrhage there was a difference between the nerve populations. Pre-aSNA responded with a marked increase within 1.5 min (159 +/- 29% of control, n = 7) and was then maintained at that level until retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Differential responses in post- and pre-ganglionic adrenal sympathetic nerve activity and renal sympathetic nerve activity after injection of 2-deoxy-D-glucose and insulin in rats.

The aim of the study was to compare pre-ganglionic adrenal nerve activity (pre-aSNA) to post-ganglionic adrenal nerve activity (post-aSNA) in rats after administration of 2-deoxy-D-glucose (2-DG, 500 mg kg-1, i.v.), which mimicks a central hypoglycaemia or to the response in pre-aSNA and post-aSNA to hypoglycaemia after injection of insulin (5U). Renal postganglionic sympathetic nerve recordings (rSNA) in a separate group was used as a reference. Adrenal or renal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar-rats. Trimethaphan, a short-lasting ganglionic blocker, was administered i.v. (10 mg kg-1) in order to test for pre- or post-aSNA in the adrenal nerves. The adrenal nerves was considered to contain predominantly post or preganglionic fibres, respectively if the nerve activity in the adrenal nerve decreased (post-aSNA) or increased (pre-aSNA). In contrast, all renal nerves showed almost a pure postganglionic activity. Post-aSNA responded with a tendency to increase after the 2-DG injection. The highest value (percentage change from control) 5 min after injection was 12 +/- 9%. The pre-aSNA increased with values of 99 +/- 52% at 3 min and 86 +/- 31% at 5 min (percentage change from control). The activity in the rSNA was only slightly decreased after the injection of 2-DG when compared to pre-drug control activity. There was a significant difference between the pre-aSNA vs. post-aSNA at 1 min (P less than 0.05), 3 min (P less than 0.01) and 5 min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Evidence for intracellular down-regulation of the epidermal growth factor (EGF) receptor during adenovirus infection by an EGF-independent mechanism.

We have reported previously that human group C adenoviruses down-regulate the epidermal growth factor (EGF) receptor (EGF-R) (C. R. Carlin, A. E. Tollefson, H. A. Brady, B. L. Hoffman, and W. S. M. Wold, Cell 57:135-144, 1989). Expression of a 13.7-kDa protein encoded by a gene in the E3 transcription unit is necessary and sufficient for this effect (Carlin et al., Cell, 1989; B. L. Hoffman, A. Ullrich, W. S. M. Wold, and C. R. Carlin, Mol. Cell. Biol. 10:5521-5524, 1990). We show here that EGF-R down-regulation is accelerated in cells which overexpress the receptor when these cells are infected with virus mutants that overproduce the 13.7-kDa protein compared with wild-type virus. This is in contrast to EGF stimulation, for which others have shown that high concentrations of ligand are associated with low rates of receptor internalization in EGF-R-overexpressing cells (D. Kuppuswamy and L. J. Pike, J. Biol. Chem. 264:3357-3363, 1989; H. S. Wiley, J. Cell Biol. 107:801-810, 1988). We also show that the E3 protein is not present in media conditioned by infected cells and that it does not induce secretion of an EGF-like autocrine factor. Moreover, while mature membrane-bound EGF-R is down-regulated, the precursor of the membrane-bound form is not. Adenovirus infection also does not affect receptor-related molecules expressed in the secretory pathway. Interestingly, adenovirus-induced down-regulation is not regulated by concentrations of EGF associated with a slow rate of internalization in A431 cells. This suggests that 13.7-kDa protein expression triggers receptor entry by a novel ligand-independent pathway or, alternatively, that it compensates for a cellular factor that may be rate limiting during EGF-mediated endocytosis.

Adenoviruses, Human↗

Health hazards in the semiconductor industry. A review.

The development of semiconductor production has been accompanied by an increased use of toxic production materials and an increased release of potential toxic wastes, which are harmful to health and environment. This paper gives an overview of occupational health hazards resulting from production materials in the microelectronics industry and from waste products originating as gases from plasma etching processes in photolithography during semiconductor production. The paper proposes methods for using experimental toxicology to investigate the occupational risks from complex mixtures of chemicals in the semiconductor industry.

Hazardous Substances↗

Diagnostic value of DNA analysis in effusions by flow cytometry and image analysis. A prospective study on 102 patients as compared with cytologic examination.

One hundred twenty-six effusion samples from 102 patients were examined by cytology and flow cytometry (FCM). Overall, there was an 84% correlation between cytologic and FCM results. Of the 36 malignant cases determined by cytologic examination, FCM revealed an aneuploid peak in 20 (56%). Image analysis (IA) performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks. In addition, FCM indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign (false negative). Aneuploidy was therefore detected in 64% of the malignant effusion specimens by FCM and IA. Twenty-three of the total of 24 aneuploid cases detected by FCM were associated with malignancy (predictive value = 96%). The one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst. FCM is an excellent tool when moderate to large numbers of tumor cells are present, whereas use of IA is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed. When an aneuploid peak is present, a diagnosis of malignancy must be suspected, and, if the initial cytologic screen is negative, a critical review of the cytology slides is justified. In those cases with an equivocal atypical cytology report and an abnormal cytometric histogram, additional investigation is warranted. In some malignancies the tumor cells will be diploid (in this study 36%) and neither FCM nor IA will add to tumor detection, leaving cytologic examination as the definitive technique.

Adult↗

[Echocardiography from the gastric fundus. Description of new projections].

Two new transgastric echocardiographic views obtained using the transesophageal probe are described. The first one (RVOT-MPA view) presents RVOT, pulmonic valve and proximal MPA. The second one (LVOT--Ao view) shows ascending aorta, aortic valve, LVOT, perimembranous area and anterior part of the trabecular septum, mitral valve with its attachment to the anterior papillary muscle and LA. The latter view corresponds to the standard subcostal view. Repeatability and applicability of these two scans were investigated on 25 pts: 10 with valvular heart disease (including 2 after valve replacement and 1 intraoperative study), 3-VSD, 2-TF, 2-ASD II, 5 with aortic aneurysm (including 1 after surgery), 3 after MI. RVOT-MPA view was obtainable in 76% pts, whereas LVOT-Ao view in 84% pts. This latter scan appeared to be very helpful in detecting VSD--either isolated perimembranous or malalignment in TF. In one pt with TF the detailed anatomy of RVOT, MPA and pulmonic arteries could be clearly imaged in fashion resembling standard echocardiographic subcostal short axis view. Left ventricular--right atrial communication was also readily appreciated in one of the pts. This view confirmed also some other informations, previously achieved by means of TEE planes (eg thrombus in LAA, aortic intimal flap protruding into LVOT). RVOT-MPA projection did not reveal more anatomical data than standard TEE planes in the investigated group. However, it should be useful in diagnosing subpulmonic VSD because of its similarity to the corresponding view available with newer TEE probes which provide longitudinal scans of the heart. The results presented proved usefulness of the new echocardiographic views, particularly in detecting VSD and more complex heart defects.

Aortic Dissection↗

[Spontaneous dissection of the distal anterior interventricular artery during intravenous thrombolysis].

A case is reported of spontaneous coronary dissection in a 55-year-old patient with an anterior myocardial infarction treated by intravenous thrombolysis. The angiographic appearance was highly characteristic with successive opacification of the true then the false channel involving the entire distal third of the anterior interventricular artery. The outcome was immediately favourable. Spontaneous dissection of coronary arteries is rare. The etiology is discussed and there is not standard management approach.

Aortic Dissection↗

Prolonged aldose reductase inhibition in chronic peripheral diabetic neuropathy: effects on microangiopathy.

A 2-year randomized placebo-controlled double-blind trial of 250 mg day-1 of the aldose reductase inhibitor Sorbinil in severe symptomatic chronic peripheral neuropathy was performed in 21 diabetic patients. Due to adverse reactions 8 patients completed the trial on Sorbinil and 6 patients on placebo. Despite differences in baseline neurophysiological parameters, duration of diabetes, and presence of retinopathy between the placebo and treatment groups, there were no initial differences in in vitro platelet aggregation, albumin excretion rate (AER) or muscle capillary basement membrane thickness. After 2 years the median deterioration in AER in the placebo group was 18.4 micrograms min-1 (range 2.6-64.8 micrograms min-1). This deterioration was significant (p less than 0.03). The change in AER in the Sorbinil group was +1.25 (-10.7 to +20.4) micrograms min-1, an insignificant change. In vitro platelet responsiveness to collagen and adenosine diphosphate (ADP) increased in the placebo group (median change max% collagen + 8 (+2 to +30)%; ADP +4.5 (0 to +20)% compared with a fall in the Sorbinil treated patients (median change; collagen -17.5 (-2 to -40)%, p less than 0.05; ADP, -4 (0 to -25)%, p less than 0.05). Muscle capillary basement membrane thickness was measured in only 3 patients in each group and did not alter significantly during the trial. All 12 neurophysiological measurements showed no significant changes between the treatment and placebo groups. The data suggest that aldose reductase inhibition has effects on platelet reactivity and microalbuminuria.

Aldehyde Reductase↗

Impact of microangiopathy on chronic symptomatic peripheral neuropathy.

The role of microvascular disease in the aetiology of diabetic peripheral neuropathy remains controversial. Muscle capillary basement membrane thickening (MCBMT) and increased albumin excretion rates (AER) are features of generalized diabetic microangiopathy and may relate to the severity of neuropathy. We have studied 19 patients with neuropathy of greater than 12 months duration and assessed relationships between the severity of neuropathy and MCBMT, AER, presence of retinopathy, age and duration of diabetes. Nine patients had retinopathy and 10 did not. The two groups of patients were well matched for age, type of diabetes and HbA1% but diabetic patients with retinopathy had significantly longer duration of diabetes (median duration 22 yr, range 3-42 yr compared with patients without retinopathy (6 yr range 1-20 yr p less than 0.05). The group with retinopathy had significantly greater median MCBMT 3,077 A (range 741-10,732 A) than their age matched non-diabetic controls 2,256 A (1,290-4,406 A p less than 0.02) or the 10 diabetic patients without retinopathy 1,599 A (805-5,152 A). The patients with retinopathy also had greater median AER 88 micrograms/min (range 8-200 micrograms/min) compared with patients without retinopathy 8 micrograms/min (2-63 micrograms/min p less than 0.05), and had significantly more severe neuropathic features on a 12 point neurophysiological ranking scale (p less than 0.05). This study showed an association between retinopathy and severity of neuropathy but there were no associations between severity of neuropathy or AER with MCBMT. Severe chronic peripheral neuropathy is associated with microangiopathic complications.

Albuminuria↗

[Acute toxoplasmic myocarditis. A cause of sudden death in a case of acquired immunodeficiency syndrome].

A case of acquired immunodeficiency syndrome with a sudden death due to a toxoplasmic myocarditis is reported. The diagnosis was postmortem. At the autopsy, only the heart was affected by toxoplasmic lesions. The toxoplasmosis is a frequent disease in AIDS patients. So a toxoplasmic myocarditis must be suspected when a severe cardiac dysfunction is observed in these patients.

Acquired Immunodeficiency Syndrome↗

Differentiated responses of renal and adrenal sympathetic nerve activity to intravenous morphine administration in anesthetized rats.

The aim of this study was to examine the effect of i.v. morphine on sympathetic nerve activity (SNA) in the rat. Adrenal SNA and renal SNA were recorded simultaneously, together with mean arterial pressure and heart rate, in chloralose-anesthetized, artificially ventilated rats. Separate groups of rats were subjected to vagotomy. In intact rats, i.v. injection of morphine (1 mg/kg) caused an immediate transient depressor response. Within 1-3 sec, renal SNA was markedly inhibited in parallel with hypotension and bradycardia. After a few minutes, mean arterial pressure and renal SNA returned toward base-line levels, and subsequently they declined gradually again below base line. Adrenal SNA, however, showed an immediate brief increase. In the vagotomized rats, an extended renal SNA excitation occurred, accompanied by a rise in mean arterial pressure. After about 15 min, these variables returned toward base-line levels. The adrenal SNA excitation still occurred in the vagotomized rats. The renal depressor and the renal and adrenal pressor responses were all abolished by naloxone pretreatment. It is concluded that i.v. injection of morphine induces a highly differentiated response of SNA. A pronounced immediate increase in adrenal SNA occurs in parallel with renal SNA inhibition. The renal nerve inhibition is mainly reflexly obtained by opioid receptor-mediated activation of vagal afferents. The predominant central action of morphine seems to be sympathetic excitation which is also mediated through opioid receptors.

Animals↗

[Angiosarcoma of the pericardium. Anatomoclinical study of a case].

We report a case of angiosarcoma of the pericardium in a 62-year-old man. Although the lack of myocardial adhesions allowed complete surgical exeresis, and despite chemotherapy, the patient died three months later because of early recurrence. Large, undifferentiated areas were found within the tumor, raising diagnostic problems with other malignant tumors of the heart. Histochemical, immunohistochemical, and ultrastructural studies confirmed the diagnosis of angiosarcoma.

Heart Neoplasms↗

[Ultrasonographic evaluation of pulmonary to systemic flow ratio. Personal experience].

Usefulness of a noninvasive, ultrasound method for pulmonary to systemic flow ration evaluation (one of the basic parameters characterizing hemodynamic disorders in cardiac defects with a left-to-right intracardiac shunt) was assessed. For that reason 153 systemic and pulmonary flows examinations of 116 patients were performed. 4 of them due to unsatisfactory quality were excluded from the further analysis. 112 remainings were divided into three groups: I. The control group without an intracardiac shunt. II. The group with a left-to-right intracardiac shunt. III. Before and after defect repair. ASD or VSD were proved or excluded basing on 2-DE. Blood flows were simultaneously with 2cDE detected using pulsed, continuous and color doppler methods. Pulmonary and systemic flow volumes were calculated by means of a combined echocardiographic and doppler method. Those volumes ratio is equal to the parameter in question. In 12 cases due to disturbed flow in mai pulmonary artery, pulmonary blood flow was measured on the mitral valve (in 11 cases) or on the right ventricular outflow tract level (in 1 patient). Systemic blood flow volume was always measured on the aortic valve level. High concordance of noninvasive calculations of pulmonary and systemic blood flow volumes was stated with differences between them not exceeded more than 20% and with correlation ratio r = 0.94. Increased pulmonary flow and pulmonary to systemic flow ratio were stated in patients with intracardiac shunt. That ratio became normal after surgical correction. There were studied changes in pulmonary and systemic flow volumes before and after a defect closure. Obtained results proved usefulness of noninvasive, ultrasound assessment of pulmonary to systemic flow ratio in a left-to-right intracardiac shunt. Some potentially encountered difficulties of the method, when its applied, was also discussed.

Adolescent↗

[Cardiac involvement in carriers of the human immunodeficiency virus. Report of 38 cases].

The anatomopathological study of the heart, carried out during the autopsy of a series of 38 subjects seropositive for the human immunodeficiency virus, has enabled the observation of histological lesions in 23 cases (60%). The heart affection is more often asymptomatic since it has been clinically suspected in only four cases. A myocarditis is present in 42 p. cent of the cases, and lesions specific to a pathogenic agent are visible in half of the myocarditis cases. These pathogenic agents are: toxoplasma (2 cases), cryptococcus (2 cases), candida (1 case), aspergillus (1 case) and cytomegalovirus (1 case). Lymphocytic myocarditis, with no isolated aetiological agent, and without viral inclusion, has been observed in 9 cases. The histological affection of the pericardium is observed in 4 cases and that of the endocardium in 3 cases. The lesions are not specific. The cardiotropism of the HIV is suspected, but not established. It could explain the frequency of lymphocytic myocarditis and dilated cardiomyopathies observed in HIV positive patients. The frequency of heart localizations in HIV positive subjects, even strictly asymptomatic as observed in this study, leads us to advise a systematic specialized cardiac examination.

Acquired Immunodeficiency Syndrome↗