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Biomedical subjects

W Schramm

Publications and source records attributed to W Schramm.

At least 91 records · Page 5Linked to original sources

[Thromboembolism prevention with low dose heparin and spinal anesthesia--a risky combination?].

UNLABELLED: Spinal or intracranial haematoma is a rare but severe complication of spinal/epidural anaesthesia with an incidence of less than 1:100,000. Coagulation defects, traumatic puncture, and anticoagulant drugs are assumed to be risk factors for the development of this kind of haematoma. Whether the risk of bleeding after spinal/epidural anaesthesia is increased by the administration of low-dose heparin (unfractionated or fractionated) for thromboprophylaxis is currently under discussion. METHODS AND RESULTS: A randomised, prospective trial answering this question is not feasible because of the rarity of the complication. As an alternative, we identified all case reports described in the literature to date and analysed them for possible risk factors. In conjunction with spinal/epidural anaesthesia, we found 4 cases of spinal and 2 cases of intracranial haematoma following treatment with unfractionated heparin and 6 cases of spinal haematoma following treatment with different low-molecular-weight (LMW) heparins. In none of these cases could thromboprophylaxis with heparin be identified as the only risk factor for bleeding: in 11 of the 12 cases a difficult or traumatic puncture was described. Eleven patients showed three or more possible risk factors, e.g., coagulation defects, concomitant therapy with other anticoagulant drugs, or anatomic abnormalities. CONCLUSION: We suggest that the development of spinal or intracranial haematoma after spinal/epidural anaesthesia is a multifactorial event. An influence of low-dose heparin prophylaxis as a cofactor cannot wholly be excluded because of the difficulty of studying the problem in a prospective way. The few case reports have to be seen in the context of millions of patients who have received either unfractionated or LMW heparin and lumbar or thoracic regional anaesthesia without any complication. We conclude that low-dose heparin prophylaxis (fractionated or unfractionated) is not a definite contraindication to spinal/epidural anaesthesia. High-risk (ASA III/IV) patients in particular benefit from effective postoperative analgesia achieved by local anaesthetics in combination with effective heparin thromboprophylaxis. Nevertheless, the absolute contraindications for regional anaesthesia must be respected and an individual risk/benefit analysis should be performed for every patient. An adequate time interval between application of heparin and regional anaesthesia or removal of a spinal/epidural catheter, atraumatic puncture technique, and careful neurologic monitoring during the post-operative period can minimise the risk of complications.

Anesthesia, Spinal↗

The inhibition of human immunodeficiency virus proteases by 'interface peptides'.

The active human immunodeficiency virus type 1 (HIV-1) protease has a homodimeric structure, the subunits are connected by an 'interface' beta-sheet formed by the NH2- and COOH-terminal amino acid segments. Short peptides derived from these segments are able to inhibit the protease activity in the range of micromolar IC50 values. We have further improved the inhibitory power of such peptides by computer modelling. The best inhibitor, the palmitoyl-blocked peptide Pam-Thr-Val-Ser-Tyr-Glu-Leu, has an IC50 value of less than 1 microM. Some of the peptides also showed very good inhibition of the HIV-2 protease. The C-terminal segment of the HIV-1 matrix protein, Acetyl-Gln-Val-Ser-Gln-Asn-Tyr, also inhibits HIV-1 protease. Kinetic studies confirmed the 'dissociative' mechanism of inhibition by the peptides. Depending on the peptide structure and ionic strength, both dimerization inhibition and competitive inhibition were observed, as well as synergistic effects between competitive inhibitors and interface peptides.

Antiviral Agents↗

Tracheobronchial ruptures in children.

Tracheobronchial ruptures in children after blunt trauma are rare, with an incidence at our clinic of 0.17% of juvenile thoracic injuries in the years 1985 to 1994. The symptoms are variable, and these injuries frequently occur in conjunction with other thoracic injuries, leading to delays in diagnosis. Diagnosis, conservative and operative treatment, and late complications are discussed by presenting four different cases of children with lesions of the tracheobronchial tree after blunt trauma.

Adolescent↗

A field test for the detection of antibodies to human immunodeficiency virus types 1 and 2 in serum or plasma.

In response to the need for simple and rapid tests for infectious diseases, we have devised a test for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 which resembles many contemporary strip-style pregnancy tests in format and ease of use. The test was evaluated with 2,928 serum specimens (1,541 reactive and 1,387 nonreactive) collected and tested at a Mexico City hospital clinic and was compared with a laboratory assay (Abbott) performed simultaneously. The sensitivity and specificity of the test using these serum specimens were 99.68 and 99.71%, respectively (before the code of the blinded study was broken). This compares with 100% sensitivity and 97.55% specificity with the laboratory assay (specificity upon reassay after the code was broken, 99.21%). In a survey of HIV-2 specimens, reactive (positive) specimens were detected in 51 of 51 cases. The test was examined with 21 commercially available (HIV-1) seroconversion panels. The performance of the test was comparable to that of a group of Food and Drug Administration-approved (antibody-based) HIV tests.

Double-Blind Method↗

Simplified testing for antibodies to human immunodeficiency virus.

Test strips for the detection of antibodies to human immunodeficiency virus type 1 were investigated using specimens from risk groups in Thailand (141 reactive; 445 nonreactive) in a local Thai laboratory. The diagnostic sensitivity and specificity were both 100%. Using a set of seroconversion panels, the sensitivity of the test strips was within the range of sensitivities obtained with enzyme immunoassays. The test was developed for performance at decentralized settings under nonlaboratory conditions.

AIDS Serodiagnosis↗

The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy/safety profile of a low-molecular-weight heparin (enoxaparin). The Prime Study Group.

In a multicentre, randomized, double-blind controlled trial comparing the low-molecular-weight heparin enoxaparin (40 mg) with a standard unfractionated heparin (Ca-heparin, 3 x 5,000 U) in deep-vein thrombosis prophylaxis in a high-risk group of 959 hospitalized medical patients, enoxaparin was at least as efficacious as standard heparin, with fewer adverse events.

Aged↗

[Economic evaluation of medical therapy--methodological principles].

Economic evaluations represent an excellent instrument to prepare decisions in health care with special reference to the allocation of resources as well as the utilisation of new and existing medical interventions and therapies. These evaluations require the identification and assessment of the costs and benefits of the various options prior to their integration in the economic calculations. The basic principles and concepts of economic evaluations are reviewed and discussed. In addition the significance of clinical, resp. medical economics will be reviewed as an important tool for the clinician.

Cost-Benefit Analysis↗

[Socioeconomic studies of hemostaseologic therapy and anticoagulation].

Since hemostaseologic therapies have a great impact on the budget of public health insurance companies, the therapy of hemophilia, prophylaxis of thrombosis and thrombolysis should be evaluated in a socioeconomic way. The substitution therapy in hemophilia is consuming a great deal of health care resources. The patients require an expensive, chronic therapy which enables them to be integrated in a normal social life. A lot of patients get a prophylaxis against thrombosis. Anticoagulants have to be valued with respect to their cost-effectiveness-relation. If thrombolysis is evaluated economically, one will have to consider carefully the high letality of thrombosis, the savings for the prevention of an operation and the high impact of this therapy on health care bills. The steady increase in health care costs emphasizes the necessity of health economics. Physicians should run socioeconomic evaluations to prove the use of different medicines and therapies and to represent the clinical point of view and the part of the patients.

Anticoagulants↗

Antinociceptive properties of protein C in a model of inflammatory hyperalgesia in rats.

We investigated the role of human protein C in an animal model of inflammatory hyperalgesia. Pain was induced by intraplantar injection of carrageenan (3 mg) into the hind paw of rats. The pain threshold was measured by exerting increasing amounts of pressure (in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg) was administered intravenously immediately after carrageenan. Controls received either intraplantar injections of saline (100 microliters) instead of carrageenan or carrageenan alone. Effects on pain threshold were expressed in percent of the pretreatment value. Carrageenan alone lowered the mean pain threshold after 3 h to 33.2 +/- 2.2% of the pretreatment level. Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with saline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinociceptive effect. Protein C had no effect in animals not preconditioned with intraplantar carrageenan. Thus protein C clearly antagonized the inflammatory pain induced by carrageenan. The antinociceptive action of protein C was antagonized by injection of a monoclonal antibody against protein C, providing additional evidence that the effect was protein C-mediated.

Animals↗

Weak allergenicity of recombinant hirudin CGP 39393 (REVASC) in immunocompetent volunteers. The European Hirudin in Thrombosis Group (HIT Group).

BACKGROUND: As a result of their polypeptidic nature, hirudins could theoretically elicit an immunologic response in humans. METHODS: The present open survey evaluates the allergenic potential of recombinant hirudin CGP 39393 (REVASC) after repeated intravenous or subcutaneous exposures in immunocompetent volunteers with no known previous exposure to hirudins. Clinical signs and symptoms of allergic manifestations and surrogate markers of allergy (i.e. response to skin tests) were collected before and after each administration of CGP 39393. Hirudin-specific immunoglobulin (Ig)G or IgE antibodies were measured. RESULTS: Two hundred and sixty-three healthy volunteers were eligible, of whom 12.2% had a history of allergy and 18.3% had a high level of total IgE. No signs or symptoms of allergy directly attributable to CGP 39393 were reported, either during or immediately after a first challenge. Irritative skin reactions, to either the prick or the intradermal skin test, were observed in eight volunteers 28-56 days after the challenge. Three out of 200 volunteers exposed to a second course of CGP 39393 showed signs and symptoms of an allergic reaction. In all but one subject with a pruritic erythema it was possible to rule out a causative role for CGP 39393 (0.50%, 95% confidence limits [CL] 0.01-2.75). Three other volunteers displayed a suspect or a positive immediate-type skin reaction to the follow-up intradermal skin test without any signs or symptoms of allergy. Another asymptomatic volunteer (0.80%, 95% CL: 0.02-4.41) developed a low [i.e. 1+ on the radio-allergosorbent test (RAST) scale] but measurable titre of hirudin-specific IgE antibodies after the second exposure to CGP 39393. A third exposure in five volunteers was clinically uneventful. A positive reaction to the prick test and to the intradermal skin test was observed in one individual. CONCLUSIONS: Recombinant hirudin CGP 39393 appears to be a weak allergen. Repeated exposures are safe in fully immunocompetent subjects, including those with a history of previous allergies and high levels of total IgE. Type I allergic reactions are rare (i.e. less than 1%) after a second exposure and are limited to the skin. Routine skin tests are not needed to identify patients at risk of developing type I allergic reactions. Hirudin-specific IgE antibodies are rarely seen and then at very low titres.

Adult↗

[Emergency management of ruptured/dissecting aortic aneurysm--diagnosis and therapeutic strategies].

Between December 1991 and January 1994 fifteen patients with a ruptured abdominal aortic aneurysm and seven patients with a dissecting aortic aneurysm were treated in our emergency department. Dissection/rupture of an aortic aneurysm is still a dramatic event with poor outcome, whereby survival depends largely on early diagnosis. In most cases the diagnosis can be made with reasonable assurance by history taking and physical examination. The most frequent differential diagnoses are pulmonary embolism and myocardial infarction (thoracic aneurysms) and renal or biliary colic and lumbago (abdominal aneurysms). The largest delay in commencing therapy is caused by patients' hesitation to call the Emergency Medical Service. Chest X-ray, echocardiography and abdominal sonography are of high diagnostic value, computed tomography confirms the diagnosis in most cases. Our Emergency Department provides the facilities for rapid diagnosis and interdisciplinary preoperative management of dissecting/ruptured aortic aneurysms.

Adult↗

Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations.

Separate single nucleotide mutations have been identified in two unrelated homozygous type I protein C deficient individuals suffering from thrombophilia. Each mutation, initially established by direct DNA sequencing of polymerase chain reaction amplification products, results in an amino acid substitution. The first mutation (PCClamart) results in an Ala136 to Pro substitution in the protein's second epidermal growth factor-like domain. The second mutation (PCMünchen) results in an Arg286 to His substitution in the serine protease domain. Comparison of the location of these two mutations and the relative conservation of the two regions in homologous vitamin K-dependent plasma proteins is consistent with the difference in severity of protein C deficiency and disease in the two individuals. Both mutations result in the abolition of a naturally occurring restriction endonuclease site, thereby allowing independent confirmation of the mutations and rapid and unambiguous genetic analysis of protein C deficiency in family members. In both families, the genetic analysis has proven useful in cases where an assignment of the protein C status based upon clinical laboratory measurements was either ambiguous or incorrect.

Adolescent↗

Prenatal care access and pregnancy outcomes in Missouri.

Women's access to prenatal care and perception of barriers to obtaining care were acquired from data derived from the 1990 NICHD/Missouri Maternal and Infant Health Survey. Maternal surveys were available for 479 fetal deaths, 902 VLBW, 802 MLBW, and 919 normal birth weight infants. Very low birth weight mothers were less likely to receive prenatal care, perceived more barriers to obtaining prenatal care, and were more unhappy about their pregnancy than were the mothers of normal weight infants.

Female↗

Black-white disparities in health status in Missouri.

Historically, the overall health status as measured by life expectancy and infant mortality of Black and White Missourians has been significantly different. We analyzed birth, death, child death and communicable disease data to determine if Blacks have narrowed the gap in health status. The overall health status of Black and White Missourians improved over the last two decades. However, the gap in health status still remains, and in some cases, has gotten worse. This occurred despite the increase in health care financing through Medicare and Medicaid. To narrow the gap in health status between Blacks and Whites requires addressing prevention and the social problems along with the medical problems.

Adolescent↗