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1.
Anaesth Rep ; 9(2): e12137, 2021.
Article in English | MEDLINE | ID: mdl-34820627

ABSTRACT

A 66-year-old man experienced symptomatic pneumorrhachis (air within the spinal canal) following a cervical laminoplasty for the excision of meningioma. Following an uneventful intraoperative course, he suffered a fluctuating hemiparesis of varying severity. Urgent imaging demonstrated extradural and intradural air in the spinal canal. Treatment with supplemental oxygen and dexamethasone was commenced, and the patient's symptoms improved over a period of three days with full resolution at six weeks. Pneumorrhachis can be avoided by allowing air to escape from the spinal canal through positioning, and displacement with irrigation fluid at the time of wound closure. However, if pneumorrhachis does occur, oxygen therapy, positioning of the patient to mitigate the gravitational effect of the air bubbles and supportive treatment are the central elements of management. Other possible causes of neurological deficit should be ruled out. This is particularly important as treatment options for some differential diagnoses can potentially cause harm if started based on clinical impression alone, for example, re-exploration for suspected haematoma. Only a small number of previous reports have described symptomatic pneumorrhachis as a complication of spinal surgery. This patient was successfully managed with conservative measures following the exclusion of other spinal cord pathologies.

2.
Nature ; 592(7856): 704-707, 2021 04.
Article in English | MEDLINE | ID: mdl-33911275

ABSTRACT

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data1,2, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole3,4. Here we report observations of QPEs in two further galaxies, obtained with a blind and systematic search of half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow that is typical of active galactic nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the QPEs reported here are inconsistent with current models that invoke radiation-pressure-driven instabilities in the accretion disk5-9. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than that of the main body10, and future X-ray observations may constrain possible changes in their period owing to orbital evolution. This model could make QPEs a viable candidate for the electromagnetic counterparts of so-called extreme-mass-ratio inspirals11-13, with considerable implications for multi-messenger astrophysics and cosmology14,15.

4.
Environ Monit Assess ; 190(6): 329, 2018 May 05.
Article in English | MEDLINE | ID: mdl-29730718

ABSTRACT

This study evaluated an 8-year dataset (2007 to 2015, except 2008) in the attempt to identify the most susceptible periods for the occurrence of diarrheic shellfish poisoning (DSP) episodes associated with the presence of toxigenic dinoflagellates, Dinophysis spp., in the mussel farming area of Babitonga Bay (southern Brazil). Dinophysis acuminata complex was the most frequent (present in 66% of the samples) and abundant (max. 4100 cells L-1) taxon, followed by D. caudata (14%; max. 640 cells L-1) and D. tripos (0.9%; max. 50 cells L-1). There was a marked onset of the annual rise in Dinophysis spp. abundance during weeks 21-25 (early winter) of each year, followed by a second peak on week 35 (spring). Mussel (Perna perna) samples usually started testing positive in DSP mouse bioassays (MBA) in late winter. Positive results were more frequent in 2007 and 2011 when the mean D. acuminata complex abundance was ~ 500 cells L-1. Although positive DSP-MBA results were observed in only 11% of the samples during the studied period, the toxin okadaic acid (OA) was present in 90% of the analyzed mussels (max. 264 µg kg-1). MBA results were positive when D. acuminata complex cell densities exceed 1200 ± 300 cells L-1, while trace toxin amounts could be detected at cell densities as low as 150 ± 50 cells L-1 (free OA) to 200 ± 100 cells L-1 (conjugated OA). Low salinity and the meteorological conditions triggered by La Niña events were the main factors associated with both Dinophysis abundance and OA accumulation in mussels.


Subject(s)
Aquaculture , Environmental Monitoring , Estuaries , Marine Toxins/metabolism , Perna/physiology , Water Pollutants, Chemical/metabolism , Animals , Bivalvia , Brazil , Dinoflagellida , Marine Toxins/analysis , Mice , Seafood , Seasons , Shellfish/analysis , Shellfish Poisoning , Water Pollutants, Chemical/analysis
5.
Anaesthesist ; 66(10): 803-826, 2017 Oct.
Article in German | MEDLINE | ID: mdl-29018871

ABSTRACT

The number of patients treated with cardiac implantable electronic devices (CIED) is continously increasing. Knowledge of the medical indications and technical mode of functioning of these devices is a basic prerequisite for the safe perioperative care of this patient cohort. The CIEDs are subjected to a multitude of disturbing influences in the perioperative setting. This can result in potentially dangerous complications, such as exit block and oversensing. The safe performance of interventions is possible as long as some basic rules are followed. An interdisciplinary approach involving all participating disciplines is necessary in order to adequately deal with the high demands placed on the logistics.


Subject(s)
Defibrillators, Implantable , Perioperative Care/methods , Humans , Intraoperative Complications/prevention & control , Perioperative Period
7.
Braz J Biol ; 74(3): 529-37, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25296199

ABSTRACT

Six blooms of Heterosigma akashiwo (Raphidophyceae) were observed from March 2007 through March 2008 in the Rodrigo de Freitas Lagoon, a semi-confined eutrophic system located in Rio de Janeiro state, southeast Brazil. Vegetative cells of H. akashiwo analysed by optical and electron microscopy showed morphology as described in the literature. The blooms (2.8 × 10(4) to 4 × 10(8) cell.L(-1)) were restricted to the middle section of the Piraquê Channel, which is situated in the northeastern part of the lagoon and receives freshwater inflow. The salinity of subsurface water and the channel depth showed significant negative correlations with H. akashiwo abundances, and appeared to restrict the blooms to this compartment of the lagoon. No fish mortality was associated with the H. akashiwo blooms, nor were brevetoxins detected in a cell extract obtained from the bloom observed on 19 March 2007.


Subject(s)
Environmental Monitoring , Eukaryota/growth & development , Lakes , Brazil , Population Density , Seasons
8.
Pneumologie ; 68(4): 270-6, 2014 Apr.
Article in German | MEDLINE | ID: mdl-24615665

ABSTRACT

Pleural effusion often represents the first clinical symptom of lung carcinoma and malignant mesothelioma. As pleural punctation is performed quite early in the diagnostic procedure, effusion cytology frequently gives the first evidence about the presence of tumour cells and tumor histogenesis. In this study, we report on seven cases which were evaluated in our institution for the Employers' Liability Insurance Association, based solely on cytology findings.The mean age of the seven patients with a given long-term asbestos exposure during their working life was 81.7 years. On average eight smears per patient were investigated. In addition to routine cytology, immunocytochemistry, DNA image cytometry, AgNOR-analysis and fluorescence in situ hybridization were applied in a case-specific way. The results were interpreted against the clinical and occupational history of the respective patient.Definitive diagnosis could be made in six cases. In three of them, the diagnosis of malignant mesothelioma was made. Two cases were diagnosed as malignant effusion due to metastatic lung cancer. In one case, cells of high-grade Non-Hodgkin's lymphoma (NHL) were diagnosed and a malignant mesothelioma was excluded. In the last case, malignant mesothelioma could not be diagnosed unequivocally by cytology. In all seven cases, our interpretation was accepted by Employers' Liability Insurance Association. The five mesothelioma or lung cancer cases were accepted as asbestos-associated occupational disease, while the NHL case was rejected. In the last case, malignant mesothelioma was diagnosed later by autopsy, and the case was retroactively accepted as occupational disease.Cytology-based tumor diagnosis including adjuvant methods is a useful and reliable approach in cases of asbestos-associated tumours. Acceptance of occupational disease on the basis of cytological diagnoses even by the Employers' Liability Insurance Association helps avoid invasive pleural or lung biopsies in cases with an unequivocally positive effusion cytology of lung cancer or malignant mesothelioma.


Subject(s)
Asbestosis/complications , Asbestosis/pathology , Mesothelioma/complications , Mesothelioma/pathology , Pleural Effusion/etiology , Pleural Effusion/pathology , Aged , Aged, 80 and over , Humans , Insurance, Accident , Lung Neoplasms , Male , Occupational Diseases/complications , Occupational Diseases/pathology
9.
Arch Orthop Trauma Surg ; 131(4): 557-61, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21161251

ABSTRACT

INTRODUCTION: For uncemented hip arthroplasty, various cup designs are available. The threaded Weill acetabular component (Weill cup; Zimmer, Winterthur, Switzerland) has been used for more than 20 years, with poor results of the smooth threaded design. Our study was intended to assess the 17-year outcome of the rough-blasted option of the threaded Weill cup. MATERIALS AND METHODS: Between 1987 and 1988, a series of 86 rough-blasted threaded Weill cups were implanted in combination with the CLS Spotorno stem (Zimmer Ltd, Germany) The patients' mean age at the time of surgery was 50 years (range 19-67 years). 67 out of 86 hips (78%) were available for a follow-up at a mean of 17 years (range 16-18 years). Radiographs were available from 55 out of 63 unrevised hips (87%) and analyzed for radiolucency and PE wear. RESULTS: Two out of 86 cups (3%) were revised due to aseptic loosening and another two cups (3%) were awaiting revision for the same reason. Ten patients (10 cups, 12%) were lost to follow-up, and nine patients with nine cups (11%) had deceased without radiographic signs of cup failure. Cup survival with "revision or awaiting revision" as endpoint was 86% (95% CI 75-92%). No deep infections occurred, and no polyethylene insert was exchanged. The Harris hip score was excellent in 37 out of 67 clinically examined hips (55%), good in 18 hips (26%), satisfactory in 5 hips (8%) and moderate or poor in 5 hips (8%) and 2 hips (3%), respectively. CONCLUSION: The rough-blasted threaded Weill cup provides a good long-term performance in cementless total hip arthroplasty. The results compare favourably to the smooth threaded cup design.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Prosthesis Design , Adult , Aged , Arthroplasty, Replacement, Hip/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prosthesis Failure , Retrospective Studies , Treatment Outcome , Young Adult
10.
Occup Environ Med ; 62(4): 263-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15778260

ABSTRACT

AIMS: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. METHODS: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. RESULTS: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. CONCLUSION: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.


Subject(s)
Fetal Blood/chemistry , Lead/blood , Adult , Alcohol Drinking/adverse effects , Blood Pressure/physiology , Body Burden , Environmental Exposure/adverse effects , Female , Hemoglobins/analysis , Humans , Infant, Newborn , Lead/toxicity , Longitudinal Studies , Maternal-Fetal Exchange/physiology , Mothers , Pregnancy , Sickle Cell Trait/blood
11.
Obes Surg ; 14(3): 334-40, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15072654

ABSTRACT

BACKGROUND: The duodenal switch (DS) is a variant of the biliopancreatic diversion (BPD) for surgical treatment of morbid obesity. Absence of dumping syndrome leads to a high quality of life in these patients. The complexity of the laparoscopic BPD-DS is high, and the technical aspects of the duodeno-ileostomy are still under consideration. MATERIALS AND METHODS: Laparoscopic BPD-DS is described, with early surgical outcomes of 63 patients reported. We used 3 different techniques for creation of the duodeno-ileostomy, which were compared. RESULTS: 2 staple-line leaks at the gastric sleeve and 1 anastomotic leak after circular stapling of the duodeno-ileostomy occurred. In the same patient with the leak, a marginal ulcer was registered 4 months after surgery. There were no differences in the operating-time between the 3 groups. The combined linear stapled and totally hand-sewn anastomosis were the safest methods to perform the duodeno-ileostomy. Local wound infection at a trocar site (insertion of the circular stapler) was the most common local complication, occurring in 3 patients after using the circular stapling technique only. Postoperative stay was 4 to 8 days, except for the 3 patients with complications. CONCLUSION: Laparoscopic BPD-DS is an advanced, complex and feasible technique in bariatric surgery. The combined linear stapled and total hand-sewn anastomosis are not only the technically easiest procedures to perform, but also appear to be the safest techniques.


Subject(s)
Biliopancreatic Diversion/methods , Obesity, Morbid/surgery , Adult , Anastomosis, Surgical , Duodenum/surgery , Female , Humans , Ileum/surgery , Laparoscopy , Male , Middle Aged , Suture Techniques , Treatment Outcome
12.
Urology ; 61(2): 464-7, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12597982

ABSTRACT

OBJECTIVES: To determine the effectiveness of BAY 41-2272 on penile erections in an in vivo rabbit model. The nitric oxide (NO)-dependent increase of intracellular cyclic guanosine monophosphate (cGMP) by cGMP-phosphodiesterase (PDE5) inhibition has been shown to be an effective mechanism in the treatment of erectile dysfunction. Direct, NO-independent stimulation of soluble guanylyl cyclase should also lead to elevated cGMP levels in tissues and could be an attractive alternative therapeutic option for the treatment of erectile dysfunction. BAY 41-2272 is a novel non-NO-based direct stimulator of soluble guanylyl cyclase that activates purified enzyme in a synergistic fashion with NO. METHODS: BAY 41-2272 was administered to conscious rabbits intravenously (IV) and orally (PO). Erection was assessed in a time-dependent manner by measuring the length of the uncovered penile mucosa. Erections were evaluated in the absence and presence of NO (with intravenous sodium nitroprusside [SNP] as the NO donor). RESULTS: BAY 41-2272 only induced weak penile erections in conscious rabbits after IV (1 mg/kg) and PO (10 mg/kg) administration in the absence of an NO donor. However, the efficacy of BAY 41-2272 was potentiated by the simultaneous administration of SNP. Through simultaneous SNP administration, the effective doses of BAY 41-2272 were reduced significantly (minimal effective dose 0.1 mg/kg IV and 1 mg/kg PO). CONCLUSIONS: The results of this study clearly demonstrated the effect of BAY 41-2272 on penile erection in the conscious rabbit model after PO and IV administration. The time-course and onset of erection was concurrent with the stimulation by exogenous NO (SNP), suggesting that this new pharmacologic mechanism of soluble guanylyl cyclase stimulation could be used in the treatment of erectile dysfunction. Because the effect is increased by SNP, it can be expected that BAY 41-2272 would have enhanced activity during sexual arousal, when NO is produced endogenously.


Subject(s)
Guanylate Cyclase/drug effects , Nitric Oxide/pharmacology , Penile Erection/drug effects , Pyrazoles/pharmacology , Pyridines/pharmacology , Administration, Oral , Animals , Dose-Response Relationship, Drug , Guanylate Cyclase/physiology , Injections, Intravenous , Male , Models, Animal , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Nitric Oxide/administration & dosage , Nitric Oxide Donors/pharmacology , Penile Erection/physiology , Penis/blood supply , Penis/drug effects , Penis/physiology , Pyrazoles/administration & dosage , Pyrazoles/therapeutic use , Pyridines/administration & dosage , Pyridines/therapeutic use , Rabbits
13.
Biomed Tech (Berl) ; 48(12): 356-61, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14740524

ABSTRACT

Pullout of implants at the proximal and distal ends of multilevel constructs represents a common spinal surgery problem. One goal concerning the development of new spinal implants is to achieve stable fixation together with the least invasive approach to the spinal column. This biomechanical study measures the influence of different modes of implantation and different screw designs, including a new monocortical system, on the maximum pullout strength of screws inserted ventrolaterally into calf vertebrae. The force pullout of eight different groups were tested and compared. Included were three bicortical used single screws (USS, Zielke-VDS, single KASS). To further increase pullout strength either a second screw (KASS) or a pullout-resistant nut can be added (USS with pullout nut). A completely new concept of anchorage represents the Hollow Modular Anchorage System (MACS-HMA). This hollow titanium implant has an increased outside diameter and is designed for monocortical use. Additionally two screw systems suitable for bicortical use were tested in monocortical mode of anchorage (USS, single KASS). We selected seven vertebrae equal in mean size and bone mineral density for each of the eight groups. The vertebral body and implant were connected to both ends of a servohydraulic testing machine. Displacement controlled distraction was applied until failure at the metal-bone-interface occurred. The maximum axial pullout force was recorded. Mean BMD was 312 +/- 55 mg CaHA/ml in cancellous bone and 498 +/- 98 mg CaHA/ml in cortical bone. The highest resistance to pullout found, measured 4.2 kN (KASS) and 4.0 kN (USS with pullout nut). The mean pullout strength of Zielke-VDS was 2.1 kN, of single KASS 2.5 kN, of MACS-HMA 2.6 kN and of USS 3.2 kN. There was no statistically significant difference (t-test, p > 0.05) between bicortical screws and the new monocortical implant. For the strongest fixation at the proximal or distal end of long spinal constructs the addition of a second screw or a pullout-resistant nut behind the opposite cortex offers even stronger fixation.


Subject(s)
Bone Screws , Equipment Failure Analysis/methods , Internal Fixators , Lumbar Vertebrae/physiopathology , Lumbar Vertebrae/surgery , Spinal Fusion/instrumentation , Animals , Bone Density , Cattle , Humans , In Vitro Techniques , Lumbar Vertebrae/diagnostic imaging , Radiography , Reproducibility of Results , Sensitivity and Specificity , Stress, Mechanical , Tensile Strength
14.
Orthopade ; 31(5): 494-502, 2002 May.
Article in German | MEDLINE | ID: mdl-12089800

ABSTRACT

Our biomechanical in vitro tests compared the stability of the MACS HMA (Aesculap, Tuttlingen) implants to three established systems. The MACS HMA is a modular system consisting of porous hollow titanium screws with an outer diameter of 12 mm for monocortical use. We report the preliminary results of MACS HMA used for correction of scoliosis. All other implant systems used are designed with bicortical screws; one is for application with two screws/two rods and one uses a pullout-resistant nut behind the opposite cortex to increase stability. Significantly increased motion in the craniocaudal direction was recognized for bicortical standard screws (20 +/- 17 microns) compared to MACS HMA (10 +/- 11 microns) or the dual screw system (12 +/- 6 microns). Two-tailed t-test showed significantly higher stability for the dual screw system (4.2 kN) and the system with pullout-resistant nut (4.0 kN) compared to all other systems (p < 0.025 or higher). Bicortical implants (2.1-3.2 kN) and MACS HMA (2.6 kN) did not reveal significant differences in pullout strength. All biomechanical tests and in vivo use demonstrated favorable performance of MACS HMA implants.


Subject(s)
Bone Screws , Materials Testing , Prostheses and Implants , Spinal Fusion/instrumentation , Titanium , Adolescent , Animals , Biomechanical Phenomena , Cattle , Cerebral Palsy/diagnostic imaging , Cerebral Palsy/surgery , Equipment Design , Equipment Failure Analysis , Female , Humans , Imaging, Three-Dimensional , In Vitro Techniques , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Male , Postoperative Complications/diagnostic imaging , Radiography , Scoliosis/diagnostic imaging , Scoliosis/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery
15.
Biomed Tech (Berl) ; 46(4): 109-12, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11388038

ABSTRACT

Modular acetabular components with alumina ceramic liners are currently used in total hip arthroplasty, but concerns have emerged regarding their high stiffness, which could cause impairment of stability, stress-shielding phenomena, and loosening. The purpose of the present biomechanical investigation was to compare the in-vitro initial stability of a modular press-fit acetabular component using a polyethylene liner and using an alumina liner. The initial stability was investigated by measuring the micromotion between the implant and the acetabulum during the application of physiological load (2.39 kN). The micromotion of the acetabular component was investigated in 10 acetabuli using a polyethylene liner and in 10 acetabuli using an alumina liner. Micromotion was assessed at the level of the Os ilium, Os pubis, and Os ischium using 3 electromagnetic transducers. The transducers have a sensitivity of 1 micron and a range of measurement of 500 microns. All implants have been fixed on human pelves made of polyurethane. Measurement of implant micromotion showed stable conditions at the level of the three main sectors of the acetabulum during all tests. No statistically significant differences of results were observed between the group of specimens with polyethylene liner and the group of specimens with alumina liner. The mean micromotion values of the uncemented cups were similar to the mean micromotion values of 10 cemented cups investigated to achieve comparative data of stability. In conclusion, the modular acetabular components inserted using an alumina liner showed a satisfactory initial stability in-vitro. The results do not contrast with those achieved using the same cup inserted with a polyethylene liner.


Subject(s)
Acetabulum , Aluminum Oxide , Hip Prosthesis , Polyethylene , Biomechanical Phenomena , Equipment Failure Analysis , Humans , Prosthesis Design
16.
Nature ; 410(6825): 212-5, 2001 Mar 08.
Article in English | MEDLINE | ID: mdl-11242081

ABSTRACT

Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.


Subject(s)
Guanylate Cyclase/chemistry , Nitric Oxide/chemistry , Amino Acid Sequence , Animals , Antihypertensive Agents/therapeutic use , Binding Sites , Blood Pressure/drug effects , Cyclic N-Oxides/pharmacology , Cysteine/chemistry , Disease Models, Animal , Enzyme Activation , Female , Guanylate Cyclase/metabolism , Heme/chemistry , Humans , Imidazoles/pharmacology , In Vitro Techniques , Indazoles/pharmacology , Molecular Sequence Data , Photoaffinity Labels , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/pharmacology , Pyridines/pharmacology , Rats , Solubility
17.
Neurosci Lett ; 299(3): 193-6, 2001 Feb 23.
Article in English | MEDLINE | ID: mdl-11165768

ABSTRACT

While G-proteins are involved in the synaptic release machinery and also can mediate inhibition of presynaptic Ca2+ channels, we find that pertussis toxin (PTX) does not affect the amount and the time course of quantal release from motor nerve terminals on crayfish or mouse muscle. Monoquantal excitatory currents (qEPSCs) were recorded that were elicited by constant depolarisation pulses to a terminal by means of a perfused macro-patch electrode. Although presynaptic effects of PTX on output and time course of release of quanta were absent, postsynaptically the rise time of qEPCs was increased and their decay time constant reduced. Adenosine (Ad) is known to inhibit quantal release in vertebrate motor nerve terminals via PTX sensitive G-proteins, and Ad is generated during nicotinic synaptic transmission by breakdown of the co-transmitter adenosine triphosphate (ATP). As reported by others, we found in mouse muscle inhibition of quantal release after application of Ad, but in addition late facilitation. Both these effects of Ad were blocked when the muscle was pre-incubated with PTX.


Subject(s)
Excitatory Postsynaptic Potentials/drug effects , Neuromuscular Junction/drug effects , Pertussis Toxin , Presynaptic Terminals/drug effects , Receptors, Purinergic P1/drug effects , Synaptic Membranes/drug effects , Synaptic Vesicles/drug effects , Virulence Factors, Bordetella/pharmacology , Adenosine Triphosphate/metabolism , Animals , Astacoidea/cytology , Astacoidea/drug effects , Astacoidea/metabolism , Autoreceptors/drug effects , Autoreceptors/metabolism , Excitatory Postsynaptic Potentials/physiology , GTP-Binding Proteins/drug effects , GTP-Binding Proteins/metabolism , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/innervation , Muscle, Skeletal/metabolism , Neuromuscular Junction/metabolism , Presynaptic Terminals/metabolism , Receptors, Purinergic P1/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Synaptic Membranes/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Synaptic Vesicles/metabolism , Time Factors
18.
Chir Organi Mov ; 86(2): 87-97, 2001.
Article in English, Italian | MEDLINE | ID: mdl-12025051

ABSTRACT

The rationale of uncemented taper stems is based on fixation in the proximal portion of the femoral diaphysis, a self-locking principle, and a low modulus of elasticity. The aim of this study was to evaluate a collarless femoral component designed to be a three-dimensional taper for press-fit insertion with regard to clinical outcome, efficacy of fixation, incidence of osteolysis, and periprosthetic bone-remodeling. The first 48 consecutive patients (50 hips) with osteoarthritis who had had primary total hip arthroplasty using the Cerafit Multicone stem and the Cerafit Triradius-M press-fit cup with alumina-alumina pairing (Ceraver Osteal, Paris, France) were followed-up for a mean of 2.3 years (2 to 2.5 years). The mean age of patients at index operations was 52.5 years. Current criteria were used for clinical and radiological assessment. Quantitative evaluation of periprosthetic bone-remodeling was prospectively assessed using computed tomography. Clinical and radiological follow-up was obtained in all hips. Forty-nine hips (98%) were clinically rated good or excellent, one hip (2%) was rated fair, owing to a persisting limp. The mean preoperative Harris Hip Score was rated 62, and it has improved to 93.5 at the time of follow-up. One hip (2%) had marked postoperative thigh pain. This pain had disappeared at 3-month follow-up. All stems showed radiological signs of stable fixation by bone ingrowth. No stem required revision. Thirty-four hips (68%) had either no change in femoral bone density or only patchy loss of bone density isolated to Gruen zones 1 and 7. Sixteen hips (32%) had some reduction of bone density isolated to zone 1. Radiolucencies without progression were found in zones 1 and 7 in 3 hips (6%), and in zone 1 alone in 3 other hips (6%). A slight cortical hypertrophy was seen in 3 hips (6%). Twenty-three hips (46%) developed radiographic appearance of bone apposition at the stem tip as partial pedestal (19 hips) and as complete pedestal (4 hips). No signs of cup loosening were detected at follow-up. Twenty-four patients (25 hips) were eligible for computed tomography. The mean decrease of the overall bone mineral density in the metaphyseal portion of the femur one year after insertion of the stem was rated 15.4%, and the mean decrease of the cortical bone mineral density was rated 17.2%. On the other hand, a mean decrease of the cortical bone mineral density of less than 5% was observed in the diaphyseal portion of the femur around the implant. The clinical and radiological results of the Cerafit Multicone stem at a mean follow-up of 2.3 years are very promising and do not contrast with those achieved using other uncemented stems with tapered design. Furthermore, results of quantitative evaluation of periprosthetic bone-remodeling were considered satisfactory favourably with others reported in the literature using stems inserted without cemented.


Subject(s)
Arthroplasty, Replacement, Hip , Bone Remodeling , Femur , Hip Prosthesis , Adult , Aged , Bone Density , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Prosthesis Design , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
19.
BMC Pharmacol ; 1: 13, 2001.
Article in English | MEDLINE | ID: mdl-11801189

ABSTRACT

BACKGROUND: The most important receptor for nitric oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase. RESULTS: We developed a photoaffinity label (3H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of 3H-meta-PAL together with the highly purified sGC leads to a covalent binding to the alpha1-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the 3H-meta-PAL labeled sGC was fragmented by CNBr digest. The 3H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236-290 of the alpha1-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the 3H-meta-PAL. CONCLUSIONS: Our data demonstrate that the region surrounding the cysteines 238 and 243 in the alpha1-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators.


Subject(s)
Enzyme Activators/pharmacology , Guanylate Cyclase/metabolism , Indazoles/pharmacology , Nitric Oxide/metabolism , Pyrazoles/pharmacology , Pyridines/pharmacology , Animals , Cells, Cultured , Enzyme Activation , Guanylate Cyclase/genetics , Insecta/cytology , Photoaffinity Labels , Recombinant Proteins/drug effects , Recombinant Proteins/metabolism
20.
Am J Epidemiol ; 152(9): 829-37, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11085394

ABSTRACT

The pattern of blood lead during pregnancy was investigated in a cohort of 195 women who, between October 1992 and February 1995, entered prenatal care at Magee-Womens Hospital in Pittsburgh, Pennsylvania, by week 13 of pregnancy. Blood was drawn as many as five times, once in each of the first two trimesters and a maximum of three times in the third trimester. Blood lead determinations were made by atomic absorption spectrophotometry. Potential sources or modifiers of lead exposure were collected by interviews, including sociodemographic, pregnancy history, occupational, and lifestyle data. Results confirmed a previously reported U-shaped curve in blood lead concentration during pregnancy as well as findings that blood lead levels increase with age, smoking, lower educational level, and African-American race and decrease with history of breastfeeding and higher intake of calcium. Additionally, interactions were found between time since last menstrual period and both maternal age and calcium. Specifically, older mothers showed steeper increases in blood lead concentrations during the latter half of pregnancy than did younger mothers, and intake of calcium had a protective effect only in the latter half of pregnancy, an effect that became stronger as pregnancy progressed. These findings provide further evidence that lead is mobilized from bone during the latter half of pregnancy and that calcium intake may prevent bone demineralization.


Subject(s)
Bone and Bones/metabolism , Calcium, Dietary/administration & dosage , Lead/blood , Adult , Black or African American , Alcohol Drinking , Black People , Body Mass Index , Calcium, Dietary/metabolism , Cohort Studies , Educational Status , Female , Humans , Lead/metabolism , Life Style , Pennsylvania , Pregnancy , Smoking , Spectrophotometry, Atomic , Surveys and Questionnaires
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