PubMed Health⌕ Search

Biomedical subjects

D Gehring

Publications and source records attributed to D Gehring.

At least 19 recordsLinked to original sources
PubMed2003

Psychological profiles among women with vulvar vestibulitis syndrome: a chart review.

The purpose of this study was to assess the prevalence and type of psychological distress in women with vulvar vestibulitis syndrome (VVS). A retrospective chart review was conducted of all women receiving a diagnosis of VVS referred to a tertiary care facility during a two-year period. Brief psychological questionnaires, including the Personality Assessment Screener, Fear of Negative Evaluation Scale, Golombok-Rust Inventory of Sexual Satisfaction, and the Phobia Rating Scale were administered. Fifty-consecutive cases were reviewed along with 12-15 month follow-up data for 41 cases. Phobic anxiety to vaginal touch or entry was significantly higher in women with VVS than normative data. Fear of Negative Evaluation was a strong associated feature, and for 30% approached clinically significant levels. Twenty-six percent showed a moderate, while another 26% showed a mild clinically distressed profile. Negative affect and social withdrawal were among the most frequently endorsed variables. Improvement in allodynia and intercourse were both related to these psychological variables, and a multiple regression analysis supported the use of psychological instruments in addition to standard medical assessment. A subgroup of women with VVS display clinically significant broad based psychological distress that warrants additional assessment. The use of psychological questionnaires in addition to medical assessment of women with VVS may provide valuable information predictive of treatment needs and response.

Adult↗
PubMed2001

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice.

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to beta-adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.

Animals↗
PubMed2001

Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes.

Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries. Multiple growth factors and various downstream signaling pathways involving, for example, ras, gp-130 (ref. 4), JNK/p38 (refs. 5,6) and calcineurin/NFAT/CaM-kinase have been implicated in the hypertrophic response. However, there is evidence that the initial phase in the development of myocardial hypertrophy involves the formation of cardiac para- and/or autocrine factors like endothelin-1, norepinephrine or angiotensin II (refs. 7,8), the receptors of which are coupled to G-proteins of the Gq/11-, G12/13- and Gi/o-families. Cardiomyocyte-specific transgenic overexpression of alpha1-adrenergic or angiotensin (AT1)-receptors as well as of the Gq alpha-subunit, Galphaq, results in myocardial hypertrophy. These data demonstrate that chronic activation of the Gq/G11-family is sufficient to induce myocardial hypertrophy. In order to test whether Gq/G11 mediate the physiological hypertrophy response to pressure overload, we generated a mouse line lacking both Galphaq and Galpha11 in cardiomyocytes. These mice showed no detectable ventricular hypertrophy in response to pressure-overload induced by aortic constriction. The complete lack of a hypertrophic response proves that the Gq/G11-mediated pathway is essential for cardiac hypertrophy induced by pressure overload and makes this signaling process an interesting target for interventions to prevent myocardial hypertrophy.

Animals↗
PubMed1993

Effect of Hoe 140 on bradykinin-induced bronchoconstriction in anesthetized guinea pigs.

We have investigated the efficacy of the novel, highly potent, and stable B2 bradykinin (BK) antagonist Hoe 140 against BK-induced bronchoconstriction in guinea pigs via whole body plethysmography and compared different routes of administration. Our results clearly demonstrate that Hoe 140 is highly potent at inhibiting bronchoconstriction induced by either intravenous (i.v.) or inhaled BK. Intravenous BK was strongly inhibited by i.v. Hoe 140 (ID50 13.4 pmol/kg), and less by aerosolized Hoe 140 (ID50 1.34 nmol/kg). Aerosolized BK (235 nmol/kg) was strongly inhibited by 0.1 nmol/kg of aerosolized Hoe 140 given 30 min before. Hoe 140 is the first BK antagonist to effectively inhibit the bronchoconstrictor effect of aerosolized BK. The equieffective i.v. dose of Hoe 140, however, as about 100-fold higher. From the discrepancy in efficacy of Hoe 140 against i.v. and aerosolized BK, it was concluded that i.v. BK has no direct effect on the lung, in contrast to inhaled BK. Moreover, the high potency of Hoe 140 in the guinea pig lung does not confirm the hypothesis of a B3 BK receptor. Based on its high potency and good tolerability, Hoe 140 is appropriate to evaluate the role of BK in human airway diseases.

Aerosols↗
PubMed1992

Airway pharmacology of the potassium channel opener, HOE 234, in guinea pigs: in vitro and in vivo studies.

The smooth muscle relaxant effects of the novel potassium channel opener, HOE 234, were investigated in guinea pig airways and compared with those of lemakalim (BRL 38227). Both agents evoked concentration-related reduction in spontaneous tracheal tone or in the tone induced by histamine, prostaglandin E2 or carbachol. HOE 234 was more potent, particularly against carbachol, and was considerably longer acting than lemakalim in a wash-out experiment. On testing for preventive efficacy against histamine-induced bronchoconstriction in anaesthetized animals a dose-related decrease of pulmonary resistance (RL) was observed. HOE 234 given either intravenously (i.v.) or by inhalation was longer acting and 3 and 6 times more potent than lemakalim. Administration of 30 micrograms/kg i.v. HOE 234 during continuous bronchoconstriction maintained by infusion of histamine decreased RL for more than 20 min whereas the effect of 100 micrograms/kg i.v. lemakalin disappeared within 4 min. These results show that HOE 234 is effective against contractile response induced by asthma mediators in guinea pig airways and compares favourably with lemakalim. Moreover it acts on acute existing bronchospasm and therefore has the potential to act against asthma attacks.

Animals↗
PubMed1986

Cardiovascular effects of the converting enzyme inhibitor ramipril (HOE 498) in anesthetized dogs with acute ischemic left ventricular failure.

The non-sulfhydryl converting enzyme inhibitor Ramipril (HOE 498) is characterized by long lasting antihypertensive activity in man. To examine its cardiovascular potential in heart failure, ramipril was administered during acute ischemic left ventricular failure in pentobarbital anesthetized dogs, induced by repeated injections of plastic microspheres into the left main coronary artery. Repeated embolizations produced stable left ventricular (LV) pump failure characterized by LV enddiastolic pressure of 22 mmHg, reductions in LV dp/dt max and cardiac output. Blood pressure and heart rate were not changed while total peripheral resistance increased. After a stabilization period ramipril was administered in two doses at 30 or 100 micrograms/kg as an intravenous bolus followed by continuous infusion of 3 or 10 micrograms/kg/min for 150 min. Ramipril in the lower dose decreased LV enddiastolic pressure by 8 mmHg, mean pulmonary artery pressure by 4 mmHg, systemic blood pressure by 40 mmHg and total peripheral resistance by 1280 dyn x sec x cm-5. LV dp/dt max, heart rate and cardiac output remained unchanged during ramipril administration. More pronounced effects were obtained with the higher dose. In conclusion, the improvements of hemodynamics produced by ramipril during acute ischemic left ventricular failure in anesthetized dogs are best explained by a reduction in both preload and afterload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

The orally active thia-imino-prostacyclin Hoe 892: antiaggregatory and cardiovascular activities.

The short chemical half-life limits the potential therapeutic value of Prostacyclin (PGI2). Replacement of the acid-labile enolether structure of PGI2 by a beta-thia-imino group resulted in the orally active and chemically stable analogue Hoe 892. Incubation of rabbit platelet rich plasma with PGI2 and Hoe 892 caused a dose dependent inhibition of collagen and arachidonic acid (AA) induced platelet aggregation with ID50 of 4.2 and 20.1 ng/ml for PGI2 respectively 43.3 and 170.2 ng/ml for Hoe 892. These effects could be potentiated by the phosphodiesterase inhibitor theophylline. Single oral administration of Hoe 892 in conscious rabbits inhibited platelet aggregation for more than 3 hrs with an ID50 of 0.2 mg/kg using collagen and 1.5 mg/kg using AA. These doses were without influence on systemic blood pressure (BP) in conscious rabbits. Intravenous injection of Hoe 892 induced a dose dependent decrease of systemic BP in anesthetized rats (ED25 of 2.2 micrograms/kg) and in the rats with acute renal hypertension. Hoe 892 stimulated renin release in anesthetized rats. The hemodynamic profile in anesthetized dogs (0.5 micrograms/kg/min i.v.) was characterized by a decrease of systemic BP, left ventricular pressure, pulmonary artery pressure, total peripheral resistance and in increase in heart rate, cardiac output and dp/dt max, thus demonstrating arteriolar vasodilation. In conscious dogs with two kidney, two wrapped hypertension oral treatment for 1 or 5 days resulted in a marked reduction of BP.

Animals↗
PubMed1982

Evening primrose oil, a dietary prostaglandin precursor, diminishes vascular reactivity to renin and angiotensin II in rats.

Polyunsaturated fatty acids (PUFA) are biosynthetic precursors of prostaglandins (PG). Endogenous biosynthesis of PG in vessel wall and kidney contributes to the regulation of arterial blood pressure. By increasing the fraction of PUFA in the diet systemic blood pressure can be lowered while PUFA deficient diet leads to an increase in blood pressure. To evaluate the effect of an enhanced PG biosynthesis by dietary PG precursors on vascular reactivity and vascular formation of prostacyclin-like activity, the pressor response to intravenous renin and angiotensin II in rats pretreated p.o. for 3 months with evening primrose oil (EPO, 1 ml/day) was determined and the antiaggregatory activity released by aortas of treated rats studied. EPO is unique in that it contains beside linoleic acid (72%), gamma-linolenic acid itself (9%). In contrast to olive oil treated rats EPO pretreatment diminished vascular reactivity to the vasopressor stimuli of renin and angiotensin II and increased the formation of vascular prostacyclin-like activity (p less than 0.05). These studies imply the possibility of a selective modulation of PG production by dietary maneuvers.

Angiotensin II↗
PubMed1981

[Prognosis of portal hypertension in hepatitic cirrhosis of the liver (author's transl)].

Laparoscopic transhepatic measurement of pressures in the branches of the portal vein (and hepatic vein) were performed in 42 patients with hepatitic cirrhosis of the liver and compared with those obtained in patients with other defined causes of cirrhosis (alcohol, pigment, Budd-Chiari syndrome, right heart failure). Mean portal vein pressure was 27.2, mean hepatic vein pressure 14.5 mm Hg. A significant pressure difference (Kruskal-Wallis test) was present only between hepatitic cirrhosis and congestive cirrhosis, not alcohol or pigment cirrhosis. During the period of observation (1975-1978) there was a high incidence of deaths and complications in the hepatitic group compared with other forms of cirrhosis: 6 treatment-resistant and 2 successfully treated cases of bleeding from oesophageal varices. The risk of bleeding begins at a pressure above 27 mm Hg, but in individual cases it cannot be used to prognosticate.

Female↗
PubMed1980

Portal hypertension in chronic hepatitis--comparative manometric and clinico-chemical examinations.

Portal hypertension (PH) which, for patients suffering from chronic liver disease, usually determines their subsequent fate, considerably exceeds the upper limit already in chronic hepatitis. With the aid of laparoscopic transhepatic manometry (LTM) in the branches of the portal and hepatic veins we measured portal vein pressures of 17.7 and hepatic vein pressures of 12.3 mm Hg in patients with chronic persistent hepatitis (CPH). In patients with chronic aggressive hepatitis (CAH) with still only moderate fibrosis, the pressure was 18.8 (in the portal vein) and 11.0 mm Hg (in the hepatic vein) while in CAH with marked remodeling, the average pressures were 19.9 and 11.8 mm Hg respectively. The early elevation of the PH, also in CPH, is an important indication for a thorough diagnostic work-up and "aggressive" therapy of the CH.

Blood Pressure Determination↗
PubMed1980

[Portal hypertension in chronic hepatitis (author's transl)].

Portal hypertension as the basis of threatening complications determines the subsequent fate of many patients with chronic inflammatory diseases of the liver. Normal values are exceeded considerably already in chronic hepatitis, but critical levels of pressure--with respect to the danger of bleeding from oesophageal varices--are only attained when cirrhotic remodelling is complete. With the aid of laparoscopic transhepatic manometry (LTM), we measured the levels of pressure in the branches of the portal vein and the hepatic vein in 23 patients suffering from chronic hepatitis (CH). In patients with chronic persistent hepatitis (CPH), the pressure in the portal vein was 17,7, in the hepatic vein 12,3 mm Hg (n = 4). In a group of 15 patients presenting with chronic aggressive hepatitis (CAH) with marked remodelling extending to cirrhosis, the average pressures were 19,9 and 11,8 mm Hg respectively; in four patients with CAH and, as yet, only slight fibrosis, the corresponding figures were 18,8 and 11,0 mm Hg respectively. In view of the recorded incidence of bleeding in 42 patients with complete hepatic cirrhosis, the early detection and intensive treatment of CH is of particular importance.

Adult↗
PubMed1975

[Radioimmunological estimation of triiodothyronine in plasma. Diagnostic value in an area with endemic goitre (author's transl)].

In 896 patients from a low-iodine area the results of the radioimmununological triiodothyronine estimations in plasma were compared with the clinical and radioisotope findings of thyroid function. It was superior to the total thyroxine estimation (T4-test) in the differential diagnosis of hyperthyroidism. In euthyroid goitre the mean triiodothyronine concentration was significantly higher than in normal persons whereas the plasma thyroxine levels at the same time were significantly lower. Only in (primary) hypothyroidism is the triiodothyronine estimation diagnostically less important than the T4-test. In summary, the radioimmunochemical method permits a clearly more precise evaluation of thyroid function even in areas of endemic goitre.

Adolescent↗