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Biomedical subjects

W Hemmer

Publications and source records attributed to W Hemmer.

At least 37 records · Page 2Linked to original sources

Are adverse effects of sildenafil also caused by inhibition of diamine oxidase?

BACKGROUND: Sildenafil citrate (Viagra), a drug used to treat erectile dysfunctions, causes adverse reactions such as headache, flushing or nasal congestion. Sildanefil's potency as inhibitor of diamine oxidase was investigated, as side effects may also be induced by histamine itself due to an impaired histamine metabolism. METHODS: Placental diamine oxidase inhibition experiments were performed with consecutive dilutions of sildenafil citrate (10(-5) to 10(-9) mol/l). In 9 male volunteers in vivo diamine oxidase inhibition was investigated after taking 100 mg sildenafil (Viagra). RESULTS: Sildenafil citrate did not inhibit placental diamine oxidase either in vitro or in vivo. However, infusion of 300 mg of cimetidine inhibited diamine oxidase activity by 27 +/- 7% 15 min after infusion, demonstrating that drugs may inhibit diamine oxidase in vivo. CONCLUSION: As side effects of sildenafil are not caused due to inhibition of diamine oxidase, sildenafil citrate seems to be harmless for patients suffering from histamine intolerance.

Adult↗

Fate of bypass grafts onto totally occluded coronary arteries.

BACKGROUND: Chronically occluded coronary arteries often develop good collateralisation, that leads to retrograde perfusion of these vessels, as regularly seen in coronary angiograms. Retrograde perfusion constitutes a form of competitive flow, which in turn is associated with an increased risk for early bypass graft failure. The aim of our study is to investigate the patency rate of bypass grafts onto totally occluded coronary arteries, in the presence of retrograde flow. METHODS: Two groups of patients were followed up by cardiac catheterisation. One month after undergoing coronary artery bypass grafting. Group 1 (n=33) had coronary three vessel disease, with one totally occluded coronary artery and evidence of retrograde flow in the preoperative coronary angiogram. Group 2 (n=30) was the control group, with coronary three vessel disease and without totally occluded coronaries. We used internal mammary arteries and saphenous vein grafts as conduits. RESULTS: Thirty-six point thirty-six per cent of bypass grafts onto totally occluded coronaries were occluded one month postoperatively (n=12). Graft failure in the control group was 13.3%. Significance p=0.03. CONCLUSIONS: In view of our findings we conclude, that there is a significantly increased incidence of early graft failure, when totally occluded coronary arteries are revascularised, that show retrograde flow in the preoperative coronary angiogram.

Coronary Angiography↗

The ross operation in 225 patients: a five-year experience in aortic root replacement.

BACKGROUND AND AIM OF THE STUDY: The Ross operation, introduced more than 30 years ago, has recently undergone several modifications to improve both technical feasibility and results. At the authors' institution, the Ross operation, performed as root replacement in all cases, was commenced in February 1995. METHODS: A total of 225 patients (177 males, 48 females; mean age 39+/-15 years; range: 2 to 67 years) were operated on up to December 2000. Aortic regurgitation was present in 80 patients, stenosis in 69, and combined disease in 73; prostheses were replaced in three patients. Combined procedures were performed in 51 patients. Nine patients had active endocarditis. Follow up was 98% complete and totaled 471 patient-years. RESULTS: There was no early mortality, and no thromboembolic or hemorrhagic events. Complications included prolonged ventilation in two patients, perioperative myocardial infarction in three, pacemaker implants in three and perioperative bleeding in six. One patient died at 25 months from hemoptysis, and one at five months of unknown cause. In the long term, four patients required reoperation due to autograft regurgitation (one autograft repair, three autograft replacements). Routine aortic annulus support, a lowered threshold in replacing all dilated ascending aorta and keeping the autograft short to the level of the sinotubular junction seems to have prevented further autograft failure. Pulmonary homograft stenosis led to reoperation in one patient. Six patients with elevated gradients are currently under observation. Echocardiography revealed autograft median peak gradients of 5.1+/-2.8 mmHg, pulmonary homograft gradients of 14.2+/-11.5 mmHg, and no significant regurgitation, except in one additional patient with recently diagnosed aortic insufficiency (grade >2). CONCLUSION: Mid-term excellent hemodynamic results, low morbidity and reoperation requirement support the evolved root replacement technique and justify its further utilization.

Adolescent↗

Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase: role in catalysis, P-site specificity, and interaction with inhibitors.

The glycine-rich loop, one of the most important motifs in the conserved protein kinase catalytic core, embraces the entire nucleotide, is very mobile, and is exquisitely sensitive to what occupies the active site cleft. Of the three conserved glycines [G(50)TG(52)SFG(55) in cAMP-dependent protein kinase (cAPK)], Gly(52) is the most important for catalysis because it allows the backbone amide of Ser(53) at the tip of the loop to hydrogen bond to the gamma-phosphate of ATP [Grant, B. D. et al. (1998) Biochemistry 37, 7708]. The structural model of the catalytic subunit:ATP:PKI((5)(-)(24)) (heat-stable protein kinase inhibitor) ternary complex in the closed conformation suggests that Ser(53) also might be essential for stabilization of the peptide substrate-enzyme complex via a hydrogen bond between the P-site carbonyl in PKI and the Ser(53) side-chain hydroxyl [Bossemeyer, D. et al. (1993) EMBO J. 12, 849]. To address the importance of the Ser(53) side chain in catalysis, inhibition, and P-site specificity, Ser(53) was replaced with threonine, glycine, and proline. Removal of the side chain (i.e., mutation to glycine) had no effect on the steady-state phosphorylation of a peptide substrate (LRRASLG) or on the interaction with physiological inhibitors, including the type-I and -II regulatory subunits and PKI. However, this mutation did affect the P-site specificity; the glycine mutant can more readily phosphorylate a P-site threonine in a peptide substrate (5-6-fold better than wild-type). The proline mutant is compromised catalytically with altered k(cat) and K(m) for both peptide and ATP and with altered sensitivity to both regulatory subunits and PKI. Steric constraints as well as restricted flexibility could account for these effects. These combined results demonstrate that while the backbone amide of Ser(53) may be required for efficient catalysis, the side chain is not.

Animals↗

[Pili trianguli et canaliculi. A case report of uncombable hair in relation to atopic eczema and tooth anomalies].

We report on a child with pili trianguli et canaliculi. This hair shaft abnormality belongs to a heterogeneous group of diseases which are included under the synonym uncombable hair. The diagnosis was confirmed by scanning electron microscopy, revealing hair shafts with a characteristic longitudinal groove. In addition the girl suffered from atopic eczema and tooth anomalies. Our findings suggest that this disorder could represent a tricho-odontal subtype of ectodermal dysplasia.

Biotin↗

[Single coronary artery with a long left main trunk].

Coronary anomalies are rare and usually benign. The case of a symptomatic woman aged 53 years is presented. Here the single coronary artery with a long left main trunk was treated by bypass grafting.

Coronary Angiography↗

Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students.

BACKGROUND: The sensitizing potency of formaldehyde and phenol during anatomy dissecting was investigated. The objective was to determine whether exposure induces specific IgE or IgG against formaldehyde-albumin or phenol-albumin. METHODS: In 27 medical students, specific IgE against formaldehyde-albumin by RAST plus ELISA and specific IgE against phenol-albumin by ELISA were assessed. In addition, specific IgG against formaldehyde-albumin was assessed in 23 students. Symptoms before and during dissecting were assessed, and indoor formaldehyde and phenol were measured. RESULTS: Mean indoor formaldehyde was 0.265 +/- 0.07 mg/m3, and mean indoor phenol was 4.65 +/- 2.96 mg/m3. Specific IgE/IgG against formaldehyde-albumin was not found at the beginning. Four students developed specific IgE against formaldehyde-albumin (RAST classes of > or =2.0), and all four also had specific IgE in the ELISA, but IgG against formaldehyde-albumin was not found. Specific IgE against phenol-albumin was not seen. Itch and paresthesia of the hands (P<0.00001), dizziness (P<0.008), burning eyes (P<0.01), headache, sneezing, epistaxis, gingival bleeding, oral or pharyngeal itch, and shortness of breath were experienced. CONCLUSIONS: Formaldehyde exposure during dissecting may induce specific IgE, but not IgG, against formaldehyde-albumin. Sensitization did not correlate with symptoms.

Adult↗

Fern allergy.

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Allergens↗

Ash (Fraxinus excelsior)-pollen allergy in central Europe: specific role of pollen panallergens and the major allergen of ash pollen, Fra e 1.

BACKGROUND: The role of ash (Fraxinus excelsior) pollen as a cause of spring pollinosis in central Europe has received little attention. It is not clear whether ash pollen is a primary cause of sensitization or whether it is implicated through cross-sensitization to other pollens. METHODS: Over a 22-month period, ash pollen was included in a screening series for inhalant allergies. Pollen data were documented from 1976 through 1999. The frequency of IgE-binding to the ash-specific allergen Fra e 1 and pollen panallergens, respectively, was compared by Western blot between mono- (n = 6), oligo- (n = 16), and polysensitized (n=25) patients. RESULTS: Of 5,416 consecutive patients sensitized to any pollen, 920 (17.6%) had a positive skin prick test to ash. Total pollen counts varied extensively between years (229-5,351) as did peak concentrations (23-837 grains/m3/24 h). Western blotting revealed Fra e 1 sensitization in 100% of monosensitized, 93% of oligosensitized, but only 44% of polysensitized patients. IgE against profilins (Fra e 2), Ca-binding proteins (Fra e 3), and carbohydrate epitopes in the three groups was found in 0/0/17%, 0/19/31%, and 32/72/60%, respectively. At least 50% of sera from patients with Fra e 1 sensitization did not bind with the protein in Western blots under reducing conditions. CONCLUSIONS: Ash pollen should be considered a relevant factor and distinct entity in spring pollinosis. In all, only 20% of positive skin tests to ash appear to result from cross-sensitization to pollen panallergens.

Allergens↗

[Surgical treatment of atrial septal aneurysms with patent foramen ovale in patients with cerebral ischemia as an alternative to life-long anticoagulant therapy: surgical strategy and results in 5 patients].

There is a significantly higher incidence of cerebral ischemia among patients with an atrial septal aneurysm and/or a patent foramen ovale. According to the information provided by modern diagnostic procedures--and in particular by transesophageal echocardiography--two pathogenic mechanisms should be considered as possible causes of the cerebral ischemia. Thrombi may develop locally in the left atrium or atrial septal aneurysm and lead to embolization or, alternatively, thrombi from the inflow region of the inferior vena cava may become trapped in the atrial septal aneurysm and pass through the patent foramen ovale to bring about embolization in the arterial bloodstream. Current treatment consists of life-long anticoagulation with coumarin derivatives in order to prevent further neurological complications. With this treatment, however, the risk of producing hemorrhages cannot be regarded as trivial, especially in old people. Surgical intervention with the insertion of a button device has so far only been attempted in a few isolated cases, and it is in any case no use if there is only an atrial septal aneurysm without a patent foramen ovale. As an alternative to administering anticoagulants for the rest of the patient's life, we operated on five cases of atrial septal aneurysm with patent foramen ovale followed by the appearance of cerebral ischemia. As with the surgical treatment of atrial septal defects in general, the risk of the operation (or of subsequent complications) is very slight indeed. No such problems arose in any of our patients, no blood transfusions were necessary, and after short postoperative treatment they could all be discharged. For younger patients with little risk from the treatment itself, we regard surgical intervention in cases of atrial septal aneurysm with a patent foramen ovale and cerebral ischemia as an important therapeutic alternative.

Adult↗

The urgent pulmonary embolectomy: mechanical resuscitation in the operating theatre determines the outcome.

BACKGROUND: The urgent pulmonary embolectomy as a surgical treatment of acute massive pulmonary embolism (PE) is still the subject of controversial discussion regarding indication, operative technique, and prognosis. METHODS: From 10/89 to 9/97 40 patients underwent urgent exploration of the pulmonary artery with the aid of extracorporeal circulation (ECC). RESULTS: The overall operative mortality was 35%. Univariate and multivariate logistic regression analysis showed preoperative hemodynamics and cardiopulmonary resuscitation (CPR) as the most important predictive factors for outcome: mortality rate was significantly higher after CPR (=63%) than without CPR (=10%) (p = 0.001). Other factors such as immobility, overweight, and concomitant cardiopulmonary disease also had an influence on the postoperative outcome. CONCLUSIONS: Pulmonary embolectomy (on the beating heart with ECC under total bypass) under stable hemodynamics, without CPR however, still constitutes an important form of treatment of acute massive PE with excellent long-term results.

Acute Disease↗

Kinetic analyses of mutations in the glycine-rich loop of cAMP-dependent protein kinase.

The conserved glycines in the glycine-rich loop (Leu-Gly50-Thr-Gly52-Ser-Phe-Gly55-Arg-Val) of the catalytic (C) subunit of cAMP-dependent protein kinase were each mutated to Ser (G50S, G52S, and G55S). The effects of these mutations were assessed here using both steady-state and pre-steady-state kinetic methods. While G50S and G52S reduced the apparent affinity for ATP by approximately 10-fold, substitution at Gly55 had no effect on nucleotide binding. In contrast to ATP, only mutation at position 50 interfered with ADP binding. These three mutations lowered the rate of phosphoryl transfer by 7-300-fold. The combined data indicate that G50 and G52 are the most critical residues in the loop for catalysis, with replacement at position 52 being the most extreme owing to a larger decrease in the rate of phosphoryl transfer (29 vs 1.6 s-1 in contrast to 500 s-1 for wild-type C). Surprisingly, all three mutations lowered the affinity for Kemptide by approximately 10-fold, although none of the loop glycines makes direct contact with the substrate. The inability to correlate the rate constant for net product release with the dissociation constant for ADP implies that other steps may limit the decomposition of the ternary product complex. The observations that G52S (a) selectively affects ATP binding and (b) significantly lowers the rate of phosphoryl transfer without making direct contact with either the nucleotide or the peptide imply that this residue serves a structural role in the loop, most likely by positioning the backbone amide of Ser53 for contacting the gamma-phosphate of ATP. Energy-minimized models of the mutant proteins are consistent with the observed kinetic consequences of each mutation. The models predict that only mutation of Gly52 will interfere with the observed hydrogen bonding between the backbone and ATP.

Amino Acid Substitution↗