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Biomedical subjects

M Rapp

Publications and source records attributed to M Rapp.

At least 19 recordsLinked to original sources
PubMed2006

Suprathel-an innovative, resorbable skin substitute for the treatment of burn victims.

Autologous split skin grafts are the most reliable method for closing third degree burns. Under this scheme, donor sites as well as second degree burns under conservative treatment, however, would benefit from rapid wound closure. For this treatment, biological as well as synthetic materials are available. For the improvement of these materials, primary goals are pain reduction and easy handling in the absence of biological risk. From a synthetic copolymer mainly based on DL-lactic acid a new skin substitute was developed, marketed as Suprathel. Within the scope of a bicentric study Suprathel was compared versus paraffin gauze intraindividually applied on split skin donor sites. Wound pain was measured on the Visual Pain Analog Scale over a period of 10 days as the critical criterion. Accordingly Suprathel versus Omiderm were compared on second degree burns (degree 2a, partial thickness burns). In both study parts, Suprathel significantly reduced pain. Its easy handling was superior compared to other materials. The Suprathel membrane adhered rapidly to the wound thus protecting against infections and promoting wound healing. No allergic reactions were observed. The ability of the material to resorb ensured pain-free removal after complete healing of the wound.

Adult↗
PubMed2006

Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers.

OBJECTIVE: To examine the associations between postmortem Alzheimer disease (AD) neuropathology and autopsy-verified cardiovascular disease. METHODS: The authors examined 99 subjects (mean age at death = 87.6; SD = 8.7) from the Mount Sinai School of Medicine Department of Psychiatry Brain Bank who were devoid of cerebrovascular disease-associated lesions or of non-AD-related neuropathology. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) as well as coronary artery and aortic atherosclerosis, left ventricular wall thickness, and heart weight were measured. Partial correlations were used to assess the associations of the four cardiovascular variables with NPs and NFTs in the hippocampus, entorhinal cortex, and multiple regions of the cerebral cortex after controlling for age at death, sex, dementia severity, body mass index, and ApoE genotype. These analyses were also repeated separately for ApoE4 carriers and noncarriers. RESULTS: The extent of coronary artery disease and to a lesser extent atherosclerosis were significantly associated with the density of cardinal neuropathologic lesions of AD in this autopsy sample (significant correlations between 0.22 and 0.29). These associations were more pronounced for the ApoE4 allele carriers (n = 42; significant correlations between 0.34 and 0.47). CONCLUSIONS: The degree of coronary artery disease is independently associated with the cardinal neuropathological lesions of Alzheimer disease. These associations are primarily attributable to individuals with the ApoE4 allele.

Aged, 80 and over↗
PubMed2005

[Morbidity and mortality of extremely low gestational age infants in Schleswig-Holstein. Follow-up at three to six years corrected age of infants < 27 + 0 weeks gestation in Schleswig-Holstein, Germany].

BACKGROUND: Regional, population-based outcome studies of extremely preterm infants may help to assess the quality of neonatal care across centres and explain variation. PATIENTS AND METHODS: We included all extremely low gestational age infants (< 27 + 0 gestational age = ELGA) of six paediatric hospitals in Schleswig-Holstein born during 1997 to 1999. The surviving children were evaluated at the corrected age of three to six years with the developmental test ET 6-6. The end point major disability was determined as subnormal scores in the developmental test ET 6-6 (< 2 SD), or any of the following diagnoses: cerebral palsy, blindness, deafness, epilepsy and/or hydrocephalus requiring a shunt system. RESULTS: 130 infants with gestational age (GA) < 27 + 0 weeks were identified. 85 survived until discharge and 82 survived until follow-up. 63 children (77% of all possible cases) participated in the developmental test. Neonatal survival increased with gestational age: 0/1 GA = 22 weeks, 3/10 GA = 23 weeks, 12/25 GA 24 = weeks, 28/43 GA = 25 weeks, 42/51 GA = 26 weeks. At follow-up 24 children had a major disability, among those were 14 children with multiple major disabilities. There was no significant correlation between major disability and gestational age. CONCLUSIONS: In a regional neonatal care system only infants of 25 to 26 weeks gestation but not those of lower GA show good survival rates. Major disability of extremely preterm infants seems to be independent of gestational age.

Cause of Death↗
PubMed2004

Improvement of surface acoustic wave gas and biosensor response characteristics using a capacitive coupling technique.

As for many other electronic devices and circuits, electrical contact to surface acoustic wave sensors is usually made using bonding wires. This technique is known to result in reliable contact under most conditions, but it does so with several disadvantages. First, electrical contact is not reversible, impeding replacement of sensor devices. Second, bonding wires are quite delicate and should not be exposed to high gas or liquid flows. Third, the presence of bonding wires may limit the potential to miniaturize a sensor housing or flow cell. Therefore, a capacitive coupling technique was developed to replace bonding wires. This permitted redesign of flow cells and sensor arrays, resulting in flow cell volumes of 80 microL to 60 nL. As a consequence, response times were reduced to 1-2 s in gas sensing and a few minutes in liquid sensing, respectively. At the same time, sensor devices can be easily replaced, and the system is less susceptible to malfunction.

Acoustics↗
PubMed2003

In vitro and in vivo evaluations of THAM derived telomers bearing RGD and Ara-C for tumour neovasculature targeting.

As an approach to the development of specific drug delivery systems, a new class of low macromolecular carriers called 'telomers' endowed with an antitumour agent, such as arabinofuranosylcytosine (Ara-C), RGDSK peptidic sequences, as tumour targeting moieties, and tyrosine groups labelled with 125I atoms allowing the in vivo scintigraphic follow up, were synthesized. Their tumour targeting ability was assessed in vivo in mice bearing a murine B16 melanoma. The biological results showed that the presence of RGDSK sequences onto the macromolecules leads to the selective targeting and the accumulation of telomers within the vascularized zone of the tumour. Moreover, such compounds exhibited in vitro a better IC(50) (0.015 muM) than pure Ara-C and in vivo an oncostatic index higher than 160%.

Acrylates↗
PubMed2002

Simulation code for the interaction of 14 MeV neutrons on cells.

The structure of the survival curve of melanoma cells irradiated by 14 MeV neutrons displays unusual features at very low dose rate where a marked increase in cell killings at 0.05 Gy is followed by a plateau for survival from 0.1 to 0.32 Gy. In parallel a simulation code was constructed for the interaction of 14 MeV neutrons with cellular cultures. The code describes the interaction of the neutrons with the atomic nuclei of the cellular medium and of the external medium (flask culture and culture medium), and is used to compute the deposited energy into the cell volume. It was found that the large energy transfer events associated with heavy charged recoils can occur and that a large part of the energy deposition events are due to recoil protons emitted from the external medium. It is suggested that such events could partially explain the experimental results.

Cell Survival↗
PubMed2001

Circadian rhythm in NO synthase I transcript expression and its photoperiodic regulation in the rat pineal gland.

The photoneural regulation of nitric oxide synthase type I (NOS I) expression in the rat pineal was investigated using semiquantitative RT-PCR. NOS I transcript expression exhibited a daily rhythm with peak values during the night hours. The daily rhythm in NOS I transcript expression persisted under constant dark conditions and was abolished under constant light conditions. The extent of nocturnal NOS I expression was found to be dependent on the photoperiod. It was attenuated under 20 h light and 4 h dark (L:D 20:4) compared with 12 h light and 12 h dark (L:D 12:12). The present findings indicate that, in the rat pineal, NOS I transcript expression exhibits a true circadian rhythm. Further, photoperiod-induced changes in circadian transcript expression appear to be responsible for reported changes in NOS I protein expression.

Animals↗
PubMed2001

Covalent bound sensing layers on surface acoustic wave (SAW) biosensors.

This paper reports on the development of immunosensors based on commercially available surface acoustic wave (SAW) devices working at 380 MHz. Approaches for coating the sensor surface with a sensing layer of receptive biomolecules are presented and discussed. It was found that the sensitivity strongly relates to the immobilization method. Additionally, the sensitivity can be influenced by the density of accessible biomolecules on the active sensing area. Usually, by most of the standard immobilization procedures, two-dimensional layers of receptive biomolecules are obtained. We present a three-dimensional layer, which provides a higher absolute amount of recognition molecules. A dextran layer is photoimmobilized to the sensor surface and the recognition molecules are covalently embedded into the dextran matrix. The feasibility of specific immunosensing is investigated using SAW sensors connected to a fluid handling system.

Acoustics↗
PubMed2001

Interferon alpha extends the survival of human myeloma cells through an upregulation of the Mcl-1 anti-apoptotic molecule.

We have recently reported that Mcl-1, an anti-apoptotic member of the Bcl-2 family, is upregulated by interleukin (IL)-6 in human myeloma cells through the janus kinase/signal transducers and activators of transduction (JAK/STAT) pathway. In the current study, we have explored the effects of interferon (IFN)-alpha, a cytokine which has been shown to increase myeloma cell survival. Our results demonstrate that IFN-alpha potently upregulates Mcl-1 on both myeloma cell lines and purified native myeloma cells. Of note, this upregulation is not due to an induction of an IL-6 autocrine loop. Furthermore, we showed that IL-6 and IFN-alpha had no additive effect on Mcl-1 upregulation, suggesting that both cytokines act through a common mechanism. Finally, the analysis of signalling transduction pathways strongly suggests that Mcl-1 upregulation induced by IFN-alpha depends on STAT3 activation. Altogether, our data show that IFN-alpha has an IL-6-like effect on human myeloma cells and suggest that it could be deleterious in some patients.

Apoptosis↗
PubMed2001

Serine/threonine phosphatase inhibitors decrease adrenergic arylalkylamine n-acetyltransferase induction in the rat pineal gland.

Adrenergic regulation of the pineal enzyme serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87] accounts for the circadian rhythm in melatonin formation. In the present study, the role of protein phosphatases in the adrenergic regulation of rat pineal AA-NAT was investigated using specific inhibitors. In cultured pineals, the serine/threonine phosphatase type 1 and type 2A inhibitors okadaic acid and calyculin A significantly decreased adrenergically or cAMP-induced AA-NAT activity, whereas the serine/threonine phosphatase type 2B inhibitor cypermethrin and tyrosine phosphatase inhibitor dephostatin were ineffective. Reverse transcriptase-polymerase chain reaction (RT-PCR) data indicate that okadaic acid exerts its effect on cAMP-dependent AA-NAT induction by downregulating the amount of AA-NAT transcript. The 'third' messengers, inducible cAMP early repressor (ICER) and Fos-related antigene-2 (Fra-2), are believed to play a negative role in pineal AA-NAT transcription. Okadaic acid increased the cAMP responsiveness of neither ICER mRNA nor Fra-2 mRNA. Therefore, the regulatory role of pineal serine/threonine phosphatases in adrenergically stimulated AA-NAT expression probably does not depend on ICER or Fra-2.

Animals↗
PubMed2001

The Emergency Medical Treatment and Labor Act as a federal health care safety net program.

Despite the greatest economic expansion in history during the 1990s, the number of uninsured U.S. residents surpassed 44 million in 1998. Although this number declined for the first time in recent years in 1999, to 42.6 million, the current economic slow-down threatens once again to increase the ranks of the uninsured. Many uninsured patients use hospital emergency departments as a vital portal of entry into an access-impoverished health care system. In 1986, Congress mandated access to emergency care when it passed the Emergency Medical Treatment and Labor Act (EMTALA). The EMTALA statute has prevented the unethical denial of emergency care based on inability to pay; however, the financial implications of EMTALA have not yet been adequately appreciated or addressed by Congress or the American public. Cuts in payments from public and private payers, as well as increasing demands from a larger uninsured population, have placed unprecedented financial strains on safety net providers. This paper reviews the financial implications of EMTALA, illustrating how the statute has evolved into a federal health care safety net program. Future actions are proposed, including the pressing need for greater public safety net funding and additional actions to preserve health care access for vulnerable populations.

Delivery of Health Care↗
PubMed2000

A differential role of CREB phosphorylation in cAMP-inducible gene expression in the rat pineal.

In the rat pineal gland cAMP mediates nocturnal induction of the enzyme arylalkylamine N-acetyltransferase (AA-NAT) as well as of transcription factors such as inducible cAMP early repressor (ICER), Fos-related antigen-2 (Fra-2) and JunB. Cyclic AMP stimulates the phosphorylation of the DNA binding protein cAMP response element binding protein (CREB). While cAMP-induced CREB phosphorylation appears to be a prerequisite for AA-NAT and ICER gene expression, it is not known whether CREB phosphorylation accounts for the full cAMP response of the two genes. Furthermore, the significance of CREB phosphorylation in cAMP-activated Fra-2 and JunB transcription is unknown. In the present in vitro study we used the serine/threonine protein phosphatase inhibitor okadaic acid (OA) to phosphorylate CREB without altering intrapineal cAMP concentration. It was observed that OA (10(-7) M) was less effective than dibutyryl cAMP (dbcAMP; 10(-3) M) in inducing AA-NAT mRNA and ICER mRNA, respectively. On the basis of this finding, it is concluded that CREB phosphorylation alone is apparently not sufficient for the full cAMP response of the two genes. By contrast, OA and dbcAMP equally stimulated the accumulation of the mRNAs of Fra-2 and JunB. Therefore cAMP may induce Fra-2 and JunB transcripts via CREB phosphorylation. Our observations suggest that CREB phosphorylation plays a critical role in diversification of cAMP-dependent gene induction in the rat pineal.

Animals↗
PubMed2000

Toxicity and/or insufficient analgesia by opioid therapy: risk factors and the impact of changing the opioid. A retrospective analysis of 273 patients observed at a single center.

The charts of 273 cancer patients were retrospectively analyzed in order (1) to evaluate the frequency of opioid change (OCH) when adjuvants (antiemetics/laxatives) were administered on a regular basis and co-analgesic medication as indicated by the specific type of pain, (2) to define risk factors for the request of OCH, and (3) to reveal settings in which OCH may not be recommended as a first-line therapeutic intervention. Opioids used included morphine, fentanyl, 1-methadone, and buprenorphine. Out of 273 patients, 103 changed opioids at least once, with a success rate of 65%. The indications for the OCH were insufficient analgesia in 43%, intolerable side effects in 20%, both in 15%, and other reasons in 22% of patients. The frequency of OCH was not influenced by the routine use of adjuvants or co-analgesics except corticosteroids, which raises queries about the concept of an opioid-sparing effect of co-analgesics. The occurrence of intolerable side effects is thought not to be dose dependent so much as to reflect differences in the individual tolerability of a distinct opioid for whatever reason (genetically fixed or individually acquired pharmacodynamic or kinetic properties). Moreover, there was strong evidence for the existence of an unpredictable and incomplete cross-tolerance between opioids, which meant careful titration of the new opioid was required after OCH. The overall frequency of OCH was similar to that observed in previous studies in spite of the documented addition of adjuvants and co-analgesics. This retrospective study supports the notion that opioid rotation must be retained as an essential therapeutic option even with optimized adjuvant and co-analgesic regimens.

Analgesics, Opioid↗
PubMed2000

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.

Cell Survival↗
PubMed2000

Disposition in rats of N-pyridinium-propyl-cyclam, N-triethylammonium-propyl-cyclam, and N-[Triethylammonium]-3-propyl-[15]ane-N5, potential cartilage imaging agents.

Quaternary ammonium compounds are known to highly concentrate in articular cartilages after i.v. administration. This property was used to synthesize new potential radiodiagnostic agents for joint imaging. Pharmacokinetic study was performed in rats for three new compounds: N-pyridinium-propyl-cyclam (NPPC), N-triethylammonium-propyl-cyclam (NTPC), and N-[triethylammonium]-3-propyl-[15]ane-N5 (NTP 15-5). After i.v. administration, [(3)H]NPPC and [(3)H]NTPC highly and rapidly concentrated in articular cartilage, this uptake being followed by a single exponential decrease with half-lives of, respectively, 75 and 82 min. Except cartilage, only the kidney was highly labeled. After complexation of (99m)Tc by NPPC, NTPC, and NTP 15-5, only (99m)Tc-NTP 15-5 exhibited a high affinity for cartilage. On the other hand, the pharmacokinetic behavior of (99m)Tc-NTPC and (99m)Tc-NPPC was very different from those of their (3)H-labeled analogs. Concentration in cartilaginous tissues was strongly diminished, and liver and bone were highly labeled. For all labeled species, the major route of excretion was urine, and HPLC analysis showed that [(3)H]NTPC and [(3)H]NPPC were excreted under their unchanged form. On the other hand, no (99m)Tc-NTPC and (99m)Tc-NPPC were found in the urine, the radioactivity being mainly due to free technetium, contrary to (99m)Tc-NTP 15-5, which was excreted in the urine under the complexed form. These data can explain the striking differences observed between the three (99m)Tc-labeled molecules, the lack of concentration of (99m)Tc-NTPC, and (99m)Tc-NPPC in cartilages in comparison with their (3)H-labeled analogs due to an instability in vivo of these technetiated complexes.

Animals↗
PubMed1999

New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies, and antiinflammatory potency.

Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)2-methylpyridinium iodide or piroxicam-N(+) and [3-(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N(+)] were synthesized. Compounds were labeled with tritium for piroxicam-N(+) and carbon-14 for propoxicam-N(+). Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low. Only propoxicam-N(+) exhibited a sufficient water solubility to be administered intravenously. This molecule was able to restore proteoglycans biosynthesis in cultured articular chondrocytes treated with Interleukin-1beta with an efficiency identical to that of indomethacin. These results suggest that the functionalization of oxicam derivatives by a quaternary ammonium group greatly increases their affinity toward articular cartilage without eliminating their pharmacological activity. New drugs synthesized according to this scheme could be useful to obtain a significant decrease of the efficient administered dose and consequently an attenuation of adverse effects such as digestive toxicity.

Animals↗
PubMed1999

[Ciguatera poisoning. Growing differential diagnostic significance in the age of foreign tourism].

BACKGROUND: In the tropic sea there are carnivore fishes, e.g. the "peak bass", that incorporate toxin producing seaweed and can cause the ciguatera intoxication. Due to the frequent tourism to tropic regions even more cases of ciguatera intoxication can be seen in Europe. The late phase of ciguatera intoxication has hardly been recognized due to its different unspecific symptoms. In some cases ciguatera intoxication can even grow a vital threatening. CASE DESCRIPTION: Four patients from a travel group addressed us 4 and 14 days after breaking off their holidays in the Dominican republic. They presented complex neurological symptoms including paraesthesia, nervousness, inverse temperature perception, muscle cramps, headache and dizziness. The physical and apparative investigation of the patients, whose age ranked between 22 and 31 years, was totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was the clue to the symptom causing dinner at their holiday location existing of "peak bass and lemon sauce". First symptoms in all members of the travel group were diarrhea, sickness and sweating. In this late phase only a symptomatic therapy could be offered. CONCLUSION: The here described cases show the importance of a comprehensive information for tropic travellers as for physicians accounted to in the acute phase of ciguatera intoxication, because recognized early enough (within the first 24 hours) the total symptomatology of ciguatera intoxication can be prevented effectively by intravenous infusions of mannitol.

Adult↗